Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :22
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
 ╗ Next article
 ╗ Previous article 
 ╗ Table of Contents
  
Resource links
 ╗  Similar in PUBMED
 ╗  Search Pubmed for
 ╗  Search in Google Scholar for
 ╗Related articles
 ╗  Article in PDF (576 KB)
 ╗  Citation Manager
 ╗  Access Statistics
 ╗  Reader Comments
 ╗  Email Alert *
 ╗  Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
   Introduction
   Beneficial Effec...
   Molecular Mechan...
   Capsaicin and Ce...
   Oxidative Action...
   Capsaicin and ST...
   Conclusion
   References

 Article Access Statistics
    Viewed7172    
    Printed340    
    Emailed14    
    PDF Downloaded727    
    Comments [Add]    
    Cited by others 33    

Recommend this journal

 


 
REVIEW ARTICLE
Year : 2010  |  Volume : 47  |  Issue : 1  |  Page : 53-58
 

Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action


Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Oyo State, Nigeria

Date of Web Publication12-Jan-2010

Correspondence Address:
A A Oyagbemi
Department of Veterinary Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, University of Ibadan, Oyo State
Nigeria
Login to access the Email id


DOI: 10.4103/0019-509X.58860

PMID: 20071791

Get Permissions

 ╗ Abstract 

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the a principal pungent ingredient of hot red and chili peppers that belong to the plant genus Capsicum (Solanaceae). Capsaicin is a cancer-suppressing agent. It blocks the translocation of nuclear factor kappa B (NF-kB), activator protein 1 (AP-1), and signal transducer and activator of transcription (STAT3) signaling pathway that are required for carcinogenesis. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression. Cytochrome P4502E1 mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotics by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemoprevention. Therefore, the use of capsaicin as a chemopreventive agent is of immense benefit for cancer chemoprevention. The search strategy included printed journals, pubmed, and medline, using the terms 'capsaicin' and 'anticancer' citations, relevant to anticancer properties of capsaicin.


Keywords: Capsaicin, cancer chemoprevention, COX-2, NF-kB, Ap-1, Stat3


How to cite this article:
Oyagbemi A A, Saba A B, Azeez O I. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action. Indian J Cancer 2010;47:53-8

How to cite this URL:
Oyagbemi A A, Saba A B, Azeez O I. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action. Indian J Cancer [serial online] 2010 [cited 2014 Apr 23];47:53-8. Available from: http://www.indianjcancer.com/text.asp?2010/47/1/53/58860



 ╗ Introduction Top


Capsaicin (trans-8-methyl-N-Vanilyl-6-nonenamide) is the pungent ingredient found in red pepper and hot chili pepper. [1] It has principally been used as spice, food additive, as drugs. [2],[3],[4] Capsaicin belongs to the plant genus Capsicum of family Solanaceae. The effects of capsaicin on multistage carcinogenesis and mutagenesis has been extensively experimented and discussed. [5],[6],[7],[8] Capsaicin is metabolized mainly by liver CYP 450 and carboxyesterases to a wide array of O-demethylated, hydroxylated, and N-dehydrogenated products. [5],[8] Capsaicin was suggested to generate potentially toxic reactive intermediates during its metabolism; these reactive intermediates include epoxides, quinones, and phenoxy radicals, which are reported to act as suicide inhibitors of CYP2E1. [5],[8] One-electron reduction of capsaicin specifically plays a role in capsaicin metabolism. Pharmacologically, capsaicin has been documented to modulate microsomal cytochrome P450-dependent monooxygenase activities with resultant alteration of metabolism of carcinogen and other xenobiotics, to ultimate carcinogen. [8],[9],[10] Pulmonary tumours Pulmonary s induced by benzo(a)pyrene are inhibited by capsaicin with significant inhibitory effects on mutagenecity and/or covalent DNA binding of aflatoxin B 1 and tobacco-specific nitrosamine 4-(metaylntrosamino)-1-(3-pyridyl)-1-batanone (NNK). [11] However, Cytochrome P4502E1, which mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites, has been shown to be inhibited by capsaicin. [12],[13]

The methods of literature search for this review article include pubmed, medline, and printed journal articles.


 ╗ Beneficial Effects of Capsaicin on Peptic Ulcer Top


Capsaicin is found to have gastroprotective effect against experimental gastric injury when given intragastrically. Previous epidemiological and clinical data suggested that chilli ingestion may have a beneficial effect on human peptic ulcer disease. [14] Increased gastric mucus production has been suggested as one mechanism by which capsaicin and chilli exert their gastroprotective effect, and reduction in mucosal mucus depletion which has been found to act as secondary protective effect of capsaicin and chilli. [14] However, -sensitive afferent neurons have been to participate in gastric mucosal protection against ulcerogenic factors. [15] Stimulation of afferent neurons by intragastric capsaicin was therefore suggested to offer protection of the experimental animals against ethanol-induced gastric mucosa damage. [15]




 ╗ Molecular Mechanisms Associated with Capsaicin Anticancer Activities Top


A number of phytochemicals present in medicinal plants are known to possess substantial anti-carcinogenic and anti-mutagenic activities. [16],[17] Capsaicin is a known phytochemical that preferentially repress the growth of various immortalized or malignant cell lines via induction of apoptosis. [18],[19] Keisuke et al. also reported the suppression or growth of leukemic cells via induction of cycle arrest at G 0 -G 1 phase and apoptosis. [20] Induction of apoptosis is in association with significant elevation of intracellular reactive oxygen species (ROS) production in cells. Cellular proliferation is known to play a major role in multistage carcinogenesis with associated multiple genetic alterations, hence, cell proliferation is a hallmark of cancer prevention. [21],[22] Therefore, inhibitory effects of capsaicin on cancer development in multiple organs, such as, stomach, lung, and liver have been extensively documented. [5],[22].[23] These inhibitory effects of capsaicin on promoter through the inactivation of two defined eukaryotic transcription factors, nuclear factor-kappa β (NF-kB), and activator protein 1 (AP-1) have been reported. [7] Therefore, capsaicin suppresses TPA-stimulated activation of NF-kB through inhibition of IkBa degradation and blockade of the subsequent nuclear translocation of p65 in human promyelocytic leukemia HL-60 cells. [24]

Methylation of the phenolic hydroxyl group of capsaicin abolished its inhibitory effect on NF-kB DNA binding. Likewise, TPA-induced activation of AP-1 was mitigated by capsaicin treatment. [25] The aberrant activation of redox-sensitive transcription factors, such as, nuclear factor-kappa B (NF-kB), activator protein 1 (AP-1), cyclic adenosine monophosphate response element binding protein (CREB), and hypoxia inducible factor (HIF), has been found to contribute to carcinogenesis by promoting persistent inflammation, abnormal cell proliferation, evasion from apoptosis, angiogenesis, and so on. [24] Interestingly, a wide variety of dietary phytochemicals exert cancer chemopreventive properties by suppressing or blocking the inappropriate activation of aforementioned transcription factors. Also, transcription of genes involved in the activation of cellular antioxidant arsenal and carcinogen detoxification is largely regulated by another redox-sensitive transcription factor, that is, the NF-E2 related factor 2 (Nrf2), which plays a role in protecting cells / tissues from oxidative or electrophilic damage. Phytochemicals present in food potentially activate Nrf2, thereby, augmenting cellular antioxidant capacity and inducing expression of phase-2 detoxification enzymes. Hence, the modulation of cellular signaling, mediated by redox-sensitive transcription factors in the right direction represents a promising approach to achieving molecular target-based chemoprevention with edible phytochemicals. [24]

Capsaicin was shown to inhibit human cancer androgen-resistant cell line, PC-3. [26] Capsaicin -induced apoptosis in prostate cells by a mechanism involving (ROS) generation, dissipation of the mitochondrial inner transmembrane potential DeltaPsi (m), and activation of caspase 3. This suggests that capsaicin is a promising anti-tumor agent in hormone refractory prostate cancer, which is resistant to many chemotherapeutic agents. [26] Capsaicin also induces apoptosis in PC-3 cells via ROS generation, c-Jun N-terminal kinase (JNK) activation, ceramide accumulation, and extracellular signal-regulated protein kinase (ERK) activation. [27] This mechanism undoubtedly explains the mechanism underlying the antiproliferative effect of capsaicin. In recent times, the effect of capsaicin, the main pungent ingredient of hot chilli peppers, in the gene expression profile of human prostate PC-3 cancer cells has been analyzed, using a microarray approach. [28] Accordingly, the upregulation of GADD153 / CHOP, an endoplasmic reticulum stress-regulated gene has been detected. This therefore suggests that capsaicin induces the antiproliferative effect through a mechanism facilitated by endoplasmic reticulum (ER) stress in prostate PC-3 cells.


 ╗ Capsaicin and Cell Cycle Top


The cell cycle represents a series of tightly integrated events, involving the cyclins, cyclin-dependent kinases (CDKs), and some of the inhibitors of these molecules. [29],[30],[31] When activated, the CDKs provide a means for the cell to move from one phase of the cell cycle to the next (G1 to S or G2 to M). If cyclin and / or CDKs are affected, cell cycle arrest occurs. DNA damage within an intact cell results in the triggering of the apoptotic machinery. Some phytochemicals exert their anticancer activity by blocking cell cycle progression and triggering tumor cell apoptosis, which have become major indicators of an anticancer effect. [32],[33]

The tumor suppressor protein p53 regulates the cellular response to DNA damage by mediating cell cycle arrest, DNA repair, and cell death. [34],[35] The mechanisms involved in p53-mediated cell death remain controversial, and regulation of the p53 function is complicated. Phosphorylation at the Ser-15 residue of p53 is critical for p53-dependent transactivation. In addition, accumulation of p53 protein by inhibiting the interaction between p53 and MDM2, stimulates p53-dependent transactivation. [36] In response to stress signals, the levels of p53 protein are rapidly increased, and activity is enhanced after phosphorylation at the Ser-15 residue, resulting in the upregulation of the downstream genes, including the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and the proapoptotic gene Bax. In turn, increased levels of Bax induce mitochondrial depolarization, release of cytochrome c, and activation of caspase cascade, leading to apoptosis. [37],[38] Ataxia telangiectasia mutated kinase has been shown to phosphorylate the Ser-15 residue of p53, leading to apoptotic signal transduction. [39],[40] Several studies have demonstrated that the ROS generation phosphorylates and activates p53 in an ataxia telangiectasia mutated-dependent manner. [41],[42] Capsaicin also causes G1 arrest of endothelial cell through downregulation of cyclin D1 and vascular endothelia growth factor (VEGF)-induced angiogenic signaling pathways. [8] Sherr reported that cyclin D1 is required for the activity of cyclin-dependent 4(CDK4), which phosphorylates RB (retinoblastoma gene), thereby releasing E2F to mediate the transition of G1 to S , which in turn leads to DNA synthesis and cell cycle progression. [43] This pathway is blocked by capsaicin. It has been documented that other anti-angiogenic molecules such as, endostatin and curcumin also suppress retinoblastoma gene phosphorylation and DNA synthesis of endothelial cells through down regulation of cyclin D1. [42],[43],[44],[45] In fact, capsaicin was reported to block the downstream event of VEGF-induced KDR / FIK-1 signaling such as, the activation of p38 mitogen-activated protein kinase and p125 FAK tyrosine phosphorylation that are required for the mitogenic activity of VEGF in endothelial cells. [46],[47],[48] Cancer cells produce numerous blood vessels through which nutrients are siphoned from individuals carrying one form of cancer or the other. The activity of VEGF is needed to achieve this fit and is therefore dependent on its phosphorylation, before it becomes active. Capsaicin is known to block the phosphorylation of VEGF. Abnormal or improper activation of downstream transcription factor can result in uncontrolled cell growth, leading to malignant transformation, abnormal cell proliferation and growth.

Capsaicin modulates the activities of proinflammatory mediators and intracellular signaling cascades

Cytokines and chemokines have been shown to play an important role in a number of inflammatory diseases. [49] Palanki reported that in activated T cells, the transcription factors such as the activator protein-1 (AP-1), regulate the production of IL-2, matrix metalloproteinases, and the nuclear factor kappa b (NF-kB), which are essential for the transcription of proinflammatory cytokines such as 1L-1, IL-6, 1L-8, tumour necrosis factor (TNF), and the nuclear factor of activated T-cells (NFAT). [49] Interleukin-1L (IL-1α) also stimulates the production of prostaglandin E2 (PGE 2), increases the expression of COX-2 mRNA protein, phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and C-Jun N-terminal kinase (JNK). [50] COX-1 is constitutively expressed while COX-2 is essentially inducible. Therefore, the expression of COX-2 is of pathological significance in a number of chronic inflammatory diseases. Scientific documentations have shown that IL-mediated transcription of COX-2 expression is regulated by numerous factors, such as, ERK, p38, NF-kB signaling pathway, and protein kinase C. [51],[52],[53],[54],[55]

NF-kB is a dimeric protein that regulates the expression of genes involved in immune responses, inflammation, cell survival, and cancer. [54],[56] NF-kB is activated in response to various degrees of stimuli ranging from cytokines, chemokines, infectious agents, and radiation-induced DNA damage. NF- is bound to inhibitory protein Ikappa b in the cytoplasm. Phosphorylation of the 1kappa b leads to translocation of NF-kB into the nucleus where it drives the expression of target genes. [57],[58],[ 59] The inhibitory effects of capsaicin on NF-kB nuclear translocation has been extensively documented. [59],[60],[61] Topical application of capsaicin has been shown to inhibit phorbol myristate acetate (PMA) induced mouse-skin tumour formation in mouse skin blockage of cultured human leukemia HL-60 cells activation and attenuation of NF-kB and tumour promoter 12-0-tetradecanoyl phorbol-13-acetate (TPA-induced carcinogenesis. [59],[60],[62]


 ╗ Oxidative Action of Capsaicin Top


Several studies have demonstrated that ROS generation plays a significant role in phosphorylation of p53 at the Ser-15 residue. [63],[64] Similarly, capsaicin-induced apoptosis in NB4 cells and in fresh leukemic cells from patients expressing wild-type p53 was associated with a significant increase in the levels of intracellular ROS, after glutathione (GSH) depletion. Similarly, pre-treatment with N-acetylcysteine (NAC), an excellent supplier of GSH inhibited phosphorylation of p53 at the Ser-15 residue, in the presence of capsaicin, indicating that ROS acts upstream of p53 phosphorylation by capsaicin. Moreover, reduction of H 2 O 2 by inhibited phosphorylation of p53 at the Ser-15 residue. It has been suggested that generation of ROS was a representative pathway of mitochondrial disruption in a p53-independent manner. [65] However, it is probable that over generation of ROS plays some role in capsaicin-induced mitochondrial depolarization and apoptosis in p53-defective cells. [66]


 ╗ Capsaicin and STAT3 Signaling Top


Members of the signal transducer and activator of transcription (STAT) family of transcription factors have been reported to regulate the expression of gene products involved in cell survival, proliferation, chemoresistance, and angiogenesis. [67],[68] The activation of STATs involves the phosphorylation of a critical tyrosine residue by Janus-activated kinases (JAK) or the Src family kinases, leading to dimerization of STAT monomers, nuclear translocation, and binding to specific DNA response elements in the promoter region promoters of target genes. Among the STATs, STAT3 is perhaps the most intimately linked to tumourigenesis. [69] Although STAT3 is activated by interleukin-6 (IL-6), the epidermal growth factor and other growth factors. Constitutive activation of STAT3 has been discovered in a wide variety of tumours. [69],[70],[71],[72] STAT3 phosphorylation therefore plays a critical role in the transformation and proliferation of tumour cells. [70],[72] It has been found that capsaicin could suppress both constitutive and inducible STAT3 activation, and these effects are specific to STAT3, as capsaicin had no effect on STAT5 phosphorylation. Similarly, it has been observed that capsaicin suppressed nuclear translocation and the DNA-binding activity of STAT3 besides multiple myeloma cells and other forms of cancer, including head and neck cancers. Hepatocellular carcinoma, lymphomas, and leukemia also express constitutively active STAT3.The suppression of constitutively active STAT3 in multiple myeloma cells raises the possibility that this novel STAT3 inhibitor might also inhibit constitutively activated STAT3 in other types of cancer cells. STAT3 phosphorylation plays a critical role in the transformation and proliferation of tumor cells and capsaicin suppresses the expression of several STAT3-regulated proteins, including proliferative (cyclin D1), antiapoptotic (survivin, Bcl-2, and Bcl-xL), and angiogenic (VEGF) gene products. [70],[72] The downregulation of cyclin D1 expression by capsaicin correlates with suppression of proliferation and accumulation of cells in G 1 phase of the cell cycle.


 ╗ Conclusion Top


The use of phytochemicals present in fruits and vegetable has gained worldwide acceptance as a novel source of chemopreventive agents against cancer cells. These non-nutrient phytochemicals either block or reverse multistage carcinogenesis. Capsaicin, a pungent ingredient present in chili pepper has anti-inflammatory, antioxidant, antiproliferative and anti-cancer potentials. Capsaicin has chemopreventive effect against a wide of chronic inflammatory diseases, including cancer. Other potential benefits of capsaicin should be explored with the aim of brightening our understanding of the molecular mechanism associated with its anti-cancer activities.

 
 ╗ References Top

1.Surh YJ. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat Res 1999;428:305-27.  Back to cited text no. 1      
2.Iwai K, Zuzuki T, Fujiwak H. Formation and accumulation of pungent principle of hot pepper fruits, capsaicin and its analogues, in Capscicum annuum var annuum cv. Karayatsubusa at different growth stages after flowering. Agric Biol Chem 1979;43:2493-8.  Back to cited text no. 2      
3.Suzuki T, Iwai K. Constitution red pepper species: Chemistry biochemistry, pharmacology, and food science of the pungent principle of capsicum species. In: Brosi A, editor. The alkaloids. New York: Academic Press; 1984. p. 227-99.  Back to cited text no. 3      
4.Cordell GA, Araujo OE. Capsaicin: Identification, nomenclature and pharmacology. Ann Pharmacother 1993;27:330-6.  Back to cited text no. 4      
5.Surh YJ, Lee SS. Capsaicin, a double-edged sword: Toxicity, metabolism, and chemoprevent potential. Life Sci 1995;1845-55.  Back to cited text no. 5      
6.Sarah YJ, Lee SS. Capsaicin in hot chili pepper: Carcinogen, co-carcinogen in anticarcinogen? Food Chem Toxicol 1996;34:313-6.   Back to cited text no. 6      
7.Surh YJ, Han SS, Keum YS, Seo HJ, Lee SS. Inhibitory effects of curcumin and capsaicin on phorbol ester-induced activation of enkaryotic transcription factors, NF-Kappa â and AP-1. Biofactors 2000;12C:107-12.  Back to cited text no. 7      
8.Jang JJ, Kim SH, Yun TK. Ihhibitory effect of capsaicin on mouse lung tumour development. In vitro 1989;33:49-54.  Back to cited text no. 8      
9.Teel RW. Effects of capsaicin on rat liver S9-mediated metabolism and DNA binding of aflatioxin B1. Nutr Cancer 1991;15:27-32.  Back to cited text no. 9      
10.Miller CH, Zhang ZI, Hamilton SM, Teel RW. Effects of capsaicin on liver microsome metabolism of the tobacco-specific nitrosamine NNK. Cancer Lett 1993;75:45-52.  Back to cited text no. 10      
11.Morre DJ, San E, Geilen C, Wu LY, de Cabo R, Krasagakis K, et al. Capsaicin inhibits plasma membrane NADH oxidase and growth of human mouse melanoma lines. Eur J Cancer 1996;32:1995-2003.  Back to cited text no. 11      
12.Kim JD, Kim JM, Pyo JO. Capsaicin can alter the expression of turnover forming- related genes which might be followed by induction of apoptosis of a Korean stomach cancer cell line SNU-1. Cancer Lett 1994;120:235-41.  Back to cited text no. 12      
13.Kang JY, Teng CH, Wee A, Chen FC. Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat. Gut 1995;36:664-9.  Back to cited text no. 13      
14.Holzer P, Sametz W. Gastric mucosal protection against ulcerogenic factors in the rat mediated by capsaicin-sensitive afferent neurons. Gastroenterology 1986;91:975-81  Back to cited text no. 14      
15.Ito K, Nakazato T, Yamato K, Miyakawa Y, Yamada T, Hozumi N, et al. Induction of apoptosis in lenvemic cells by homova nillic acid derivation, capsaicin, through oxidative. Cancer Res 2004;64:1071-8.  Back to cited text no. 15      
16.Moore MA, Tsunda H. Chronicalla elerated Proliferation as a risk factor for neoplasm. Eur J Cancer Rev 1998;7:353-85.  Back to cited text no. 16      
17.Mori H, Sugie S, Yoshimi N, Hara, Tanaka T. Control of cell proliferation in cancer prevention. Mutat Res 1999;428:291-8.  Back to cited text no. 17      
18.Yun TK. Update from Asia: Asian study on cancer chemoprevention. Ann NY Acad Sci 1999;889:157-92.  Back to cited text no. 18      
19.Kang JY, Tang Ch, Wee A, Chen FC. Effect of capsaicin and Chilli on ethanol induced gastric mucosal in jury in the rat. Gut 1995;36:664-9.  Back to cited text no. 19      
20.Mukhopadhay A, Banergee S, Stafford LJ, Xia C, Liu M, Aggarival BB. Curcumin induced Suppression of cell proliferation correlations in the down-regualtion of cyclin D1 expression and CDK4- mediated retino blastoma protein phosphorylation. Oncogene 2002;21:8852-61.  Back to cited text no. 20      
21.Hanai J, Dhanabal M, Karumanchi SA, Albanese C, Waterman M, Chan B, et al. Eudostation causes G1 arrest of endothelial cells through inhibition of cyclin Dl. J Biol Chem 2002;277:16464-9.  Back to cited text no. 21      
22.Bernatchez PN, Soker S, Sirois MG. Vascular endothelial growth factors effect on endothelial cell proliferation, migration, and plutelet-activating factor synthesis is FLK-1-1 dependent. J Biol Chem 1999;274:31047-54.  Back to cited text no. 22      
23.Kundu JK, Surh YJ. Molecular basis of chemoprevention with dietary phytochemicals: Redox-regulated transcription factors as relevant targets, Phytochemistry Rev 2009;8:333-47.  Back to cited text no. 23      
24.Han SS, Keum YS, Chun SK, Surh YJ. Suppression of phorbol ester-induced NF-kB activation by capsaicin in cultured human promyelocytic leukemia cells. Arch Pharma Res 2002;25:475-9.  Back to cited text no. 24      
25.Sánchez AM, Sánchez MG, Malagarie-Cazenave S, Olea N, Díaz-Laviada I. Induction of apoptosis in prostate tumour PC-3 cells and inhibition of xenograft prostate tumour growth by the vanilloid capsaicin. Apoptosis 2006;11:89-99.  Back to cited text no. 25      
26.Sánchez AM, Malagarie-Cazenave S, Olea N, Vara D, Chiloeches A, Díaz-Laviada I. Apoptosis induced by capsaicin in prostate PC-3 cells involves ceramide accumulation, neutral sphingomyelinase, and JNK activation. Apoptosis 2007;12:2013-24.   Back to cited text no. 26      
27.Sánchez AM, Martínez-Botas J, Malagarie-Cazenave S, Olea N, Vara D, Lasunción MA, et al. Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: A microarray study. Biochem Biophys Res Commun 2008;372:785-91.  Back to cited text no. 27      
28.Farhana L, Dawson M, Rishi AK, Zhang Y, Van Buren E, Trivedi C. Cyclin B and E2F-1 expression in prostate carcinoma cells treated with the novel retinoid CD437 are regulated by the ubiquitin-mediated pathway. Cancer Res 2002;62:3842-9.   Back to cited text no. 28      
29.Wolter F, Akoglu B, Clausnitzer A, Stein J. Down-regulation of the cyclin D1/Cdk4 complex occurs during resveratrol induced cell cycle arrest in colon cancer cell lines. J Nutr 2001;131:2197-203.   Back to cited text no. 29      
30.Joe AK, Liu H, Suzui M, Vural ME, Xiao D, Weinstein IB. Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin Cancer Res 2002;8:893-903.  Back to cited text no. 30      
31.Paschka AG, Butler R, Young CY. Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate. Cancer Lett 1998;130:1-7.   Back to cited text no. 31      
32.Smets LA. Programmed cell death (apoptosis) and response to anti-cancer drugs. Anticancer Drugs 1994;5: 3-9.  Back to cited text no. 32      
33.Ko LJ, Prives C. p53, puzzle and paradigm. Genes Dev 1996;10:1054-72.  Back to cited text no. 33      
34.Shieh SY, Taya Y, Prives C. DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser 20, requires tetramerization. EMBO J 1999;18:1815-23.   Back to cited text no. 34      
35.Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997;91:325-34.  Back to cited text no. 35      
36.Momand J, Zambetti GP, Olson DC, George D, Levine AJ. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 1992;69:1237-45.  Back to cited text no. 36      
37.Levine AJ. p53, the cellular gatekeeper for growth and division. Cell 1997;88:323-31.   Back to cited text no. 37      
38.Jimenez GS, Khan SH, Stommel JM, Wahl GM. p53 regulation by post-translational modification and nuclear retention in response to diverse stresses. Oncogene 1999;18:7656-65.   Back to cited text no. 38      
39.Ashcroft M, Vousden KH. Regulation of p53 stability. Oncogene 1999;18:7637-43.   Back to cited text no. 39      
40.Lakin ND, Jackson SP. Regulation of p53 in response to DNA damage. Oncogene 1999;18:7644-55.   Back to cited text no. 40      
41.Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, et al. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 1998;281:1677-9.   Back to cited text no. 41      
42.Zachary I, Gliki G. Signaling transduction mechanism mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res 2001;49:568-81.  Back to cited text no. 42      
43.Davis-Smyth T, Chem H, Park J. Presta LG, Ferrara N. The second immunoglobin- line domain of the VEGF tyrosine Kinase receptor Fit-1 determines ligand binding and may initiate a signal transduction cascade. EMBO J 1996;15:4919-27.  Back to cited text no. 43      
44.Palanki MS. Inhibitors of Ap-1 and NF-KB Mediated transcriptional activation: Therapeutic potential in autoimmune diseases and structural diversity. Curr Med Chem 2002;9:219-27.  Back to cited text no. 44      
45.Ogata S, Kubota Y, Yamashiro T, Taveuchi H, Ninomiya T, Suyama Y, et al. Signaling pathways regulating IL-1<-induced COX-2 expression. J Deut Res 2007;86:186-91.  Back to cited text no. 45      
46.Mifflin RC, Saada JI, Mari JF, Adegboyega PA, Valentich JD, Powell DW. Regulation of COX-2 expression in human intestinal fibroblasts: Mechanisms of IL-1- Mediated induction. Am J Physiol Cell Physiol 2002;282:C824-34.  Back to cited text no. 46      
47.Yang CM, Chien CS, Hsi LD, Luo SF, Wang CC. Interlenken-1 B-induced COX-2 expression is mediated through activation of p42/44 and p38 MAPKS, and NF-kappa B Pathway in canine tracheal smooth muscle cells. Cells Signal 2002;14:899-911.   Back to cited text no. 47      
48.Catley DA, Newton R, Zhn YM, El-Haroum H, Corbelt L, Knox AJ. COX-2 induction by bradykinin in human pulmonary artey smooth muscle cells is mediated in the Cyclic AMP response element through novel autocrine loop involving endogenous PGE2,Eprostanood (Ep2) and Ep4 receptors. J Biol Chem 2003;278:499954-64.  Back to cited text no. 48      
49.Lin CH, Sheu SY, Lee HM, HO YS, Lee WS, Wc KO. Involvement of protein Linase C-gamma in IL-B- induced COX-2 expression in human pulmonary epithehal cells. Mol Pharmacol 2002;61:614-9.   Back to cited text no. 49      
50.Molina-Holgado F, Ortiz S, Molina-Holgado F, Guaza C. Induction of COX-2 and PGE (2) brosynthesis by IL-1 Beta is mediated by PKC and MARKS in murire astrocytes. Br J Pharmacol 2000;131:152-9.  Back to cited text no. 50      
51.Hacker H, Karin M. Regulation of function of IKK and IKK-related Kinases. Sci Stroke 2006;357:13.  Back to cited text no. 51      
52.Rothwarf DM, Karin M. The NF-Kappa B activation pathway: A parading in information transfer from membrane to nucleus. Sci Stroke 1999;5:1.  Back to cited text no. 52      
53.Dhar A, Young MR, Colburn NH. The role of Ap-1, NF-KB and ROS/NOS in skin carcinogenesis: The IB6 motel is predictive. Mol Cell Biochem 2002;235:185-93.  Back to cited text no. 53      
54.Han SS, Keum YS, Seo HJ, Chun KS, Lee SS, Surh JY. Capsaicin suppresses phorbol ester-induced activation of NF-Kappa B/Rel and AP-1 transcription factors in mouse epidermis. Cancer Lett 2001;164:119-29.  Back to cited text no. 54      
55.Han SS, Keun YS, Chun KS, Surh YJ. Suppression of Phorbor ester-induced NF-Kappa B inactivation in Capsaicin in cultured human Promyelocytic Leukemia cells. Arch Pharm Res 2002;25:475-9.  Back to cited text no. 55      
56.Han SS, Keum YS, Seo HJ, Chun KS, Lee SS, Surh YJ. Capsaicin suppresses phorbol ester-induced activation of NF-kappaB/Rel and AP-1 transcription factors in mouse epidermis. Cancer Lett 2001;164:119-26.  Back to cited text no. 56      
57.Darnell JE Jr. Transcription factors as target for cancer therapy. Nat Rev Cancer 2002;749-9.  Back to cited text no. 57      
58.Ihle JN. STATS: Signal tranducers and activators of transcription. Cell 1996;84:331-4.  Back to cited text no. 58      
59.Gao SP, Brombery JF. Touched and moved by STATS3. Sci STKE 2006;16:30.  Back to cited text no. 59      
60.Banin S, Moyal L, Shieh SY, Taya Y, Anderson CW, Chessa L, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 1998;281:1674-7.   Back to cited text no. 60      
61.Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh SY, et al. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 1999;13:152-7.  Back to cited text no. 61      
62.Ye J, Wang S, Leonard SS, Sun Y, Butterworth L, Antonini J, et al. Role of reactive oxygen species and p53 in chromium (VI)-induced apoptosis. J Biol Chem 1999;274:34974-80.   Back to cited text no. 62      
63.Vrablic AS, Albright CD, Craciunescu CN, Salganik RI, Zeisel SH. Altered mitochondrial function and overgeneration of reactive oxygen species precede the induction of apoptosis by 1-O-octadecyl-2-methyl-rac-glycero-3-phosphocholine in p53-defective hepatocytes. FASEB J 2001;15:1739-44.   Back to cited text no. 63      
64.Darnell JE Jr. Transcription factors as targets for cancer therapy. Nat Rev Cancer 2002;2:740-9.  Back to cited text no. 64      
65.Ihle JN. STATs: Signal transducers and activators of transcription. Cell 1996;84:331-4.  Back to cited text no. 65      
66.Aggarwal BB, Sethi G, Ahn KS, Sandur SK, Pandey MK, Kunnumakkara AB, et al. Targeting signal-transducer-and-activator-of-transcription (STAT)-3 for prevention and therapy of cancer: Modern target but ancient solution. Ann N Y Acad Sci 2006;1091:151-69.  Back to cited text no. 66      
67.Gao SP, Bromberg JF. Touched and moved by STAT3. Sci STKE 2006;16:30.  Back to cited text no. 67      
68.Bharti AC, Donato N, Aggarwal BB. Curcumin (diferuloylmethane) inhibits constitutive and IL-6-inducible STAT3 phosphorylation in human multiple myeloma cells. J Immunol 2003;171:3863-71.  Back to cited text no. 68      
69.Yu H, Jove R. The STATs of cancer: New molecular targets come of age. Nat Rev Cancer 2004;4:97-105.  Back to cited text no. 69      
70.Song JI, Grandis JR. STAT signaling in head and neck cancer. Oncogene 2000;19:2489-95.   Back to cited text no. 70      
71.Yoshikawa H, Matsubara K, Qian GS, Jackson P, Groopman JD, Manning JE, et al. SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity. Nat Genet 2001;28:29-35.   Back to cited text no. 71      
72.Zhang Q, Raghunath PN, Xue L, Majewski M, Carpentieri DF, Odum N, et al. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma. J Immunol 2002;168:466-74.  Back to cited text no. 72      



This article has been cited by
1 Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells
Ogunc Meral,Merve Alpay,Gorkem Kismali,Funda Kosova,Dilek Ulker Cakir,Mert Pekcan,Serbulent Yigit,Tevhide Sel
Tumor Biology. 2014;
[Pubmed]
2 Pharmacological importance of an ethnobotanical plant:Capsicum annuumL.
Farhan A. Khan,Tariq Mahmood,Muhammad Ali,Abdul Saeed,Aneela Maalik
Natural Product Research. 2014; : 1
[Pubmed]
3 Development and Validation of an HPLC-DAD Analysis for Pharmacopoeial Qualification of Industrial Capsicum Extracts
M. Kuzma,K. Fodor,B. Boros,P. Perjesi
Journal of Chromatographic Science. 2014;
[Pubmed]
4 Restoration of p53/miR-34a regulatory axis decreases survival advantage and ensures Bax-dependent apoptosis of non-small cell lung carcinoma cells
Samik Chakraborty,Minakshi Mazumdar,Shravanti Mukherjee,Pushpak Bhattacharjee,Arghya Adhikary,Argha Manna,Sreeparna Chakraborty,Poulami Khan,Aparna Sen,Tanya Das
FEBS Letters. 2014;
[Pubmed]
5 Effects of chronic elevated ozone concentration on the redox state and fruit yield of red pepper plant Capsicum baccatum
Rafael Calixto Bortolin,Fernanda Freitas Caregnato,Armando Molina Divan,Flßvio Henrique Reginatto,Daniel Pens Gelain,JosÚ Clßudio Fonseca Moreira
Ecotoxicology and Environmental Safety. 2013;
[Pubmed]
6 Expression and functionality of TRPV1 receptor in human MCF-7 and canine CF.41 cells
C. Vercelli,R. Barbero,B. Cuniberti,R. Odore,G. Re
Veterinary and Comparative Oncology. 2013; 9999(9999): n/a
[Pubmed]
7 Anti-diabetic effects of Korean red pepper via AMPK and PPAR-? activation in C2C12 myotubes
Hye Jeong Yang,Dai-Ja Jang,Jin-Taek Hwang
Journal of Functional Foods. 2012; 4(2): 552
[Pubmed]
8 Capsaicin induces de-differentiation of activated hepatic stellate cell
Shanna Bitencourt,Fernanda C. de Mesquita,Eduardo Caberlon,Gabriela V. da Silva,Bruno S. Basso,Gabriela A. Ferreira,Jarbas R. de Oliveira
Biochemistry and Cell Biology. 2012; 90(6): 683
[Pubmed]
9 Chili zur Therapie der Trigeminusneuralgie
J. Loeser,B. Pilgram,O. Dagtekin
Der Schmerz. 2012; 26(4): 435
[Pubmed]
10 Functional validation of Capsicum frutescens aminotransferase gene involved in vanillylamine biosynthesis using Agrobacterium mediated genetic transformation studies in Nicotiana tabacum and Capsicum frutescens calli cultures
Harishchandra B. Gururaj,Mallaya N. Padma,Parvatam Giridhar,Gokare A. Ravishankar
Plant Science. 2012; 195: 96
[Pubmed]
11 Capsaicin-Induced Apoptosis of FaDu Human Pharyngeal Squamous Carcinoma Cells
Thanh-Do Le,Dong Chun Jin,Se Ra Rho,Myung Su Kim,Rina Yu,Hoon Yoo
Yonsei Medical Journal. 2012; 53(4): 834
[Pubmed]
12 Role of autophagy in chemoresistance: Regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNAľPKcs and PARP-1
Jung-Hoon Yoon,Sang-Gun Ahn,Byung-Hoon Lee,Sung-Hoo Jung,Seon-Hee Oh
Biochemical Pharmacology. 2012; 83(6): 747
[Pubmed]
13 Role of autophagy in chemoresistance: Regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1
Yoon, J.-H., Ahn, S.-G., Lee, B.-H., Jung, S.-H., Oh, S.-H.
Biochemical Pharmacology. 2012; 83(6): 747-757
[Pubmed]
14 Ethnic differences in colon and rectal cancer incidence in Nigeria: A case of dietary determinants?
DavidO Irabor
Annals of Nigerian Medicine. 2012; 6(2): 71
[Pubmed]
15 Capsaicin induces de-differentiation of activated hepatic stellate cell
Bitencourt, S. and De Mesquita, F.C. and Caberlon, E. and Da Silva, G.V. and Basso, B.S. and Ferreira, G.A. and De Oliveira, J.R.
Biochemistry and Cell Biology. 2012; 90(6): 683-690
[Pubmed]
16 Functional validation of Capsicum frutescens aminotransferase gene involved in vanillylamine biosynthesis using Agrobacterium mediated genetic transformation studies in Nicotiana tabacum and Capsicum frutescens calli cultures
Gururaj, H.B. and Padma, M.N. and Giridhar, P. and Ravishankar, G.A.
Plant Science. 2012; 195: 96-105
[Pubmed]
17 Cancer: Plant based chemoprevention and therapy: An overview
Singh, L. and Pracheta
Biochemical and Cellular Archives. 2012; 12(1): 1-20
[Pubmed]
18 Chilli for therapy of trigeminus neuralgia. A case report [Chili zur Therapie der Trigeminusneuralgie Ein Fallbericht]
Loeser, J. and Pilgram, B. and Dagtekin, O.
Schmerz. 2012; 26(4): 435-437
[Pubmed]
19 A comprehensive review of the carcinogenic and anticarcinogenic potential of capsaicin
Bley, K. and Boorman, G. and Mohammad, B. and McKenzie, D. and Babbar, S.
Toxicologic Pathology. 2012; 40(6): 847-873
[Pubmed]
20 Capsaicin-induced apoptosis of FaDu human pharyngeal squamous carcinoma cells
Le, T.-D. and Jin, D.C. and Rho, S.R. and Kim, M.S. and Yu, R. and Yoo, H.
Yonsei Medical Journal. 2012; 53(4): 834-841
[Pubmed]
21 Anti-diabetic effects of Korean red pepper via AMPK and PPAR-╬│ activation in C2C12 myotubes
Yang, H.J. and Jang, D.-J. and Hwang, J.-T.
Journal of Functional Foods. 2012; 4(2): 552-558
[Pubmed]
22 Suppression of tumor necrosis factor-╬▒-induced nuclear factor ╬║b activation and aromatase activity by capsaicin and its analog capsazepine
Luqman, S. and Meena, A. and Marler, L.E. and Kondratyuk, T.P. and Pezzuto, J.M.
Journal of Medicinal Food. 2011; 14(11): 1344-1351
[Pubmed]
23 Modulatory effects of capsaicin on n-diethylnitrosamine (DEN)-induced mutagenesis in salmonella typhimurium YG7108 and DEN-induced hepatocarcinogenesis in gpt delta transgenic rats
Toyoda-Hokaiwado, N., Yasui, Y., Takamune, M., Yamada, M., Muramatsu, M., Masumura, K., Ohta, T., (...), Nohmi, T.
Genes and Environment. 2011; 33(4): 160-166
[Pubmed]
24 The two faces of capsaicin
Bode, A.M., Dong, Z.
Cancer Research. 2011; 71(8): 2809-2814
[Pubmed]
25 Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling
Hwang, Y.P., Yun, H.J., Choi, J.H., Han, E.H., Kim, H.G., Song, G.Y., Kwon, K.-I., (...), Jeong, H.G.
Molecular Nutrition and Food Research. 2011; 55(4): 594-605
[Pubmed]
26 Red pepper: Overview of potential health benefits
Singletary, K.
Nutrition Today. 2011; 46(1): 33-47
[Pubmed]
27 Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (panin) by capsaicin in lsl-krasg12d/pdx1-cre mice
Bai, H., Li, H., Zhang, W., Matkowskyj, K.A., Liao, J., Srivastava, S.K., Yang, G.
Carcinogenesis. 2011; 32(11): 1689-1696
[Pubmed]
28 Impact of dried black grape and/or hot red pepper supplementation in ameliorating the nephrotoxicity effect of cisplatin in rats
El-Wahab, H.M.F.A., Hassanin, N.I.Y., Ahmed, E.M., El-Monem, A.R.A.
Australian Journal of Basic and Applied Sciences. 2011; 5(10): 231-238
[Pubmed]
29 Chemoprevention against hepatocellular carcinoma
Okano, J.-I. and Fujise, Y. and Abe, R. and Imamoto, R. and Murawaki, Y.
Clinical Journal of Gastroenterology. 2011; 4(4): 185-197
[Pubmed]
30 Inhibition of chronic pancreatitis and pancreatic intraepithelial neoplasia (PanIN) by capsaicin in LSL-KrasG12D/Pdx1-Cre mice
H. Bai,H. Li,W. Zhang,K. A. Matkowskyj,J. Liao,S. K. Srivastava,G.-Y. Yang
Carcinogenesis. 2011; 32(11): 1689
[Pubmed]
31 Suppression of EGF-induced tumor cell migration and matrix metalloproteinase-9 expression by capsaicin via the inhibition of EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling
Yong Pil Hwang,Hyo Jeong Yun,Jae Ho Choi,Eun Hee Han,Hyung Gyun Kim,Gye Yong Song,Kwang-il Kwon,Tae Cheon Jeong,Hye Gwang Jeong
Molecular Nutrition & Food Research. 2011; 55(4): 594
[Pubmed]
32 Integrative oncology
Cassileth, B. and Rockefeller, L.S.
ONCOLOGY. 2010; 24(4)
[Pubmed]
33 Nutraceutical use in late-stage cancer
Wargovich, M.J., Morris, J., Brown, V., Ellis, J., Logothetis, B., Weber, R.
Cancer and Metastasis Reviews. 2010; 29(3): 503-510
[Pubmed]



 

Top
Print this article  Email this article
Previous article Next article

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  ę 2007 - Indian Journal of Cancer | Published by Medknow