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 » Introduction
 »  Materials and Me...
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ORIGINAL ARTICLE
Year : 2017  |  Volume : 54  |  Issue : 1  |  Page : 253-256
 

Chemosuppressive effect of plumbagin on human non-small lung cancer cell xenotransplanted zebrafish


Department of Biotechnology, St. Peter's Engineering College, Avadi, Chennai - 600054, India

Date of Web Publication1-Dec-2017

Correspondence Address:
Dr. S A Ceasar
Department of Biotechnology, St. Peter's Engineering College, Avadi, Chennai - 600054
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.219580

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 » Abstract 

BACKGROUND: Plumbagin (5-hydroxy-2-methyl-1,4-napthoquinone) derived from Plumbago species is a potential anti-tumour agent. Plumbagin has been tested for anti-cancer activity in vitro and in vivo using mice model. AIM: To study the tumour suppressing efficacy of plumbagin using zebrafish model. MATERIALS AND METHODS: Human Non-small lung cancer cell line were cultured in vitro and transplanted in to zebrafish. The development of tumour was confirmed by performing histology. The tumour was then allowed to progress in vivo and the fishes were administered with plumbagin orally for three continuous days. The tumour suppression capacity was monitored subsequently using transcriptosome analysis. STATISTICAL METHODS: The pixel integrated density obtained was converted into relative gene expression using IBM SPSS. RESULTS: The administration of plumbagin had an ability to suppress tumour and the size of the tumour were relatively lesser when compared with the control sample; it has also increased p53 gene expression. CONCLUSION: The study helps to conclude that plumbagin is an effective anti-tumour agent against human cancer cells based on the study in vivo in zebrafish.


Keywords: Danio rerio, plumbagin, p53, xenotransplantation


How to cite this article:
Vinothkumar R, Ceasar S A, Divyarupa A. Chemosuppressive effect of plumbagin on human non-small lung cancer cell xenotransplanted zebrafish. Indian J Cancer 2017;54:253-6

How to cite this URL:
Vinothkumar R, Ceasar S A, Divyarupa A. Chemosuppressive effect of plumbagin on human non-small lung cancer cell xenotransplanted zebrafish. Indian J Cancer [serial online] 2017 [cited 2020 Apr 5];54:253-6. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/253/219580



 » Introduction Top


Cancer is a disorder caused by aggressiveness, invasiveness and malignancy of a single transformed cell, which takes the nutrients from its microenvironment and grows almost unopposed. Cancer formation both in vitro and in vivo is a multistep process, which needs to overcome various barriers. However, the cancer cells have certain natural traits, which help them overcome these barriers.[1] The earliest definition of cancer was from Hippocrates of Cos, who lived during the early 400 B.C;[2] but still no definite cure has been proposed to treat cancer, this has led to their incidence and related mortality to touch new heights.

Considering the present rate, the incidence and mortality due to cancer in 2030 would be as high as 20 million and 12.4 million respectively.[2] All the therapeutic strategy available today reduces the quality of life of the patient in one way or another. A case study published on the quality of life of patients undergoing radical prostatectomy threw light on how the quality of life had deteriorated more than the actual prediction of the clinicians.[3] Therefore, there is an increasing need for an alternative therapy.

Plumbagin, a cytotoxic element extracted from Plumbago species[4] has the potential to serve this purpose. Plumbagin's effective chemosuppressive action has been demonstrated in breast cancer,[5] ovarian cancer,[6],[7] pancreatic cancer,[8] lung cancer,[9],[10] and prostate cancer.[11],[12] Plumbagin's effect on signal transduction was uncovered as plumbagin was found to increase accumulation of p53[10] and suppress NF-κB.[13] The apoptosis causing ability of plumbagin was demonstrated in vitro in human pancreatic cancer [8] and in vivo in human lung cancer.[10]

Zebrafish (Danio rerio) has the ability to develop a wide range of malignant and benign tumour with a histology that widely resembles human tumour.[14],[15] Zebrafish has a diploid genome [16] and its oncogenes and tumour suppressor genes are conserved in the humans;[17] this makes the signaling pathway follow almost the same pattern.[16] So, the action of a particular molecule in zebrafish model would more closely resemble the drug action in human. Xenotransplantation is the most advantageous tumour induction method in both zebrafish and mice model since the action of human tumours can be monitored in vivo.[18] All these makes zebrafish with Xenotransplanted human cancer, an effective model to study tumour. Considering the above facts we have undertaken this study to assay the effect of plumbagin in zebrafish. This is the first report on the effect of oral administration of plumbagin in tumour induced zebrafish model.


 » Materials and Methods Top


Cell line and growth medium

The non-small lung cancer cell line (NCI-H460) was obtained from American Type Culture Collection (ATCC, USA). The NCI-H460 cells were cultured in RPMI1640 media (Roswell Park Memorial Institute Medium 1640)[19] supplemented with 10% Fetal Bovine Serum (FBS) and 1% each of penicillin and streptomycin in an incubator with 95% of air: 5% of CO2.

Transplantation of human non-small lung cancer cells

Healthy male zebrafishes of 30-60 days old were grown in laboratory condition. The fishes required for transplantation were treated with 10 μl/ml of dexamethasone (Decdan , USA) for 2 days before induction.[20] The non-small lung cancer cell line (NCI-H460) were harvested from the cell suspension and was subjected to Trypan blue assay, live cells were segregated and mixed with 0.9% of physiological saline to make a dense cell suspension. The fishes were anesthetized in ice-cold water by slowly regulating the temperature from 17°C to 12°C.[21] Twenty micro litre of the cell suspension was injected into each fish using a 30'1/2 inch cannula syringe based on a previous study.[22] After injection, fishes were washed with distilled water to get rid of cells adhered to their body surface and were transferred to clear water to recover from anesthesia. The fishes were then randomly divided into two groups. The first group of fishes was administered with plumbagin and the other was maintained as negative control. The experiments were performed by adhering to the guidelines of the Institute of Laboratory Animal research.

Oral administration of plumbagin

Plumbagin (Modern Natural Products, Mumbai, India) was bought in a soluble form and was used for oral administration. A suggested dose of 15.6 ppm of plumbagin,[23] which was not lethal for fishes was dispensed into fish water from 3 days post induction (pi).

Histology

Zebrafishes were euthanized using isoflurene and were dissected near the intraperitoneal cavity to extract the cancerous lump. The lump was minced physically in the presence of a PBS solution to form a single cell suspension. The suspension was stained subsequently using Hematoxylin and Eosin (H and E) stain (Himedia Inc, India). After staining, the slides were subjected to microscopic examination with BX51 microscope (Olympus , USA).

RNA extraction and RT-PCR analysis

Zebrafishes from plumbagin treated and the control group were randomly selected and euthanized; tissues were drawn from cancerous and non-cancerous part of individual fishes. Total RNA was extracted using Trizol reagent (Medox Inc, India) following the single step RNA isolation method.[24] cDNA was produced by treating the total RNA with 5 U/μl reverse transcriptase (Medox Inc, India). The produced cDNA was subjected to PCR with forward (5'-CCCGCAGTCTGGCACAGCAA-3') and reverse (5'-TGGAGGGGCAACGTCCACCA-3') primers specific for p53 gene. The reaction volume was maintained at 50 μl. The amplification was done with an initial denaturating step at 94°C for 5 minutes followed by 25 cycles each with a denaturing step at 94°C for 30 seconds, a annealing step at 55°C for 30 seconds and an extension step at 72°C for 30 seconds, the final extension step lasted for 7 minutes at 72°C. The product was finally cooled to 4°C. The product was subjected to gel electrophoresis in a 3% agarose gel and viewed under a gel documentation system. The gel bands were analyzed using ImageJ software (National Institute of Health, USA) to measure pixel integrated densities using standard curve.[25]

Image analysis

All microscopic images were background subtracted using Olympus background subtraction tool kit. The gel bands were analyzed using ImageJ software (National Institute of Health, USA) to measure pixel integrated densities using standard curve.[25]

Data analysis

Since individual organisms differ in their gene expression, a relative gene expression was used to compare the results obtained from different fishes. Relative gene expression is the ratio of the pixel integrated densities of cancerous to that of non-cancerous sample obtained for the same organism. SPSS was used in the process of obtaining the relative gene expression.


 » Results Top


The aim of the study was to develop a new non-small lung cancer model by using xenotransplantation in zebrafish and to prove that plumbagin works with equal ease and up regulates p53 in the designed model.

This is the first report on tumour induced by xenotransplantation of non-small lung cancer cell line (NCI-H460) in zebrafish. The xenotransplanted fishes immunosuppressed by dexamethosone showed progressive tumour development over 15 days pi [Figure 1]. The fishes showed clear morphological distinction in the intraperitoneal cavity, where the tumour was injected. The change in morphology was evident from 3 days pi and tumour was externally visible. The induction of tumour was further confirmed by histology [Figure 2]. The presence of fused cells that had bi-lobed and tri-lobed nuclei was evident [Figure 2]a.
Figure 1: Zebrafish showing progressive tumour growth

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Figure 2: Histology of the zebrafish tumour (x40)

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Previous studies carried out using mice model [8],[10] had administered plumbagin by intraperitoneal injection. This is the first publication reporting an oral administration of plumbagin. Plumbagin was orally administered due to the fact that intraperitoneal (ip) injection of plumbagin on zebrafish caused recurring injuries and lead to the mortality of fishes, we suffered an initial set back in our experimentation due to this issue; oral administration helped us to overcome this problem. The oral administration pacified disease condition in zebrafish; there was an evident change in the size of the tumour compared to the fishes in the control group [Figure 3].
Figure 3: Suppression of tumour following administration of plumbagin

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To confirm our finding at molecular level the effect of plumbagin on genes concerned with cell-regulatory molecules was undertaken. The tumour suppressor gene p53 was our eventual choice taking into consideration its importance in gene regulation and cell differentiation. The tumour suppressor gene p53 was up regulated in plumbagin treated tissue. The amount of p53 in plumbagin treated cells were ~14 folds higher compared to the control [Figure 4]. The up regulation of p53 was similar to the results obtained in mice model.[10] The gene expression also threw light on the fact that plumbagin was specific in its action taking into consideration the difference in relative gene expression that occurred in the normal tissue.
Figure 4: The relative gene expression of plumbagin. The graph shows the expression of zebrafish administered with plumbagin and the control group

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 » Discussion Top


The advantage of inducing tumourigenicity has prompted many reports on induction of tumourigenicity in both Casper [26] and wild-type zebrafish.[27],[28] Our data demonstrates the use of non-small lung cancer cell line NCI-H460 in inducing tumourigenicity in wild-type zebrafish. Commercial anesthetics like Tricaine (3-amino benzoic acid ethyl ester) had an influence on the cardiac function of zebrafish [29] and lead to mortality of some fishes; the cold anesthesia technique reported by Kinkel et al.[21] helped to overcome this problem. Efforts to optimize and build an effective xenotransplantation protocol using human cancer cell are very much needed in order to aid us to study the disease prognosis and treatment.

The use of chemotherapeutic drugs result in a higher range of side effects and have a drastic influence on the quality of life of an individual, therefore a search for an alternative therapy is necessary. Phytochemicals, the non-nutritive components extracted from plants are being studied as one such option. Various phytochemicals and dietary supplements have been found to exert chemosuppressive effect on cancer (reviewed extensively by Surh, 2003).[30] Few phytochemicals like vinblastine and vincristine from Vinca rosea are being used in patients and many are on the development pipe line but a comprehensive cure is still evasive. Our present study of plumbagin using a xenotransplanted zebrafish model that closely resembles the niche of cancer in vivo in human being helps plumbagin stake its claim as a new drug in chemotherapy. But plumbagin too has its side effects as does with the other phytochemicals. Plumbagin has also been reported to have a negative impact on the fertility.[31] The influence on fertility would have a higher influence on AYA (Adolescent and Young Adult) patients. Taking into consideration the recent reports suggesting 26.6% of the total cases to be AYA,[32] a novel technique which imparts more specificity to plumbagin is needed.

The suppression of cancer can be correlated with the change in expression of the key cell-regulatory molecules. Termed as Guardian of genome,[33] the p53 is one such regulatory molecule that takes care of cell cycle arrest,[34] apoptosis,[35] differentiation,[36] senescence [37] and DNA repair.[35] It is capable of inducing apoptotic cell death in response to oncogenic stress by activating the transcription of pro-apoptotic genes. Phytochemicals like vinblastin,[38] capsaicin,[39] and curcumin [40] have been reported to up regulate p53. Our report suggests that p53 is up regulated on administration of plumbagin, falling in line with similar experiment in mice model.[10] The up regulation of p53 confirms the anti-tumourigenic potential of plumbagin in a genetic level. Neither the present study nor any previous study has strived to unlock the molecule or the receptor to which plumbagin interacts to cause apoptosis by triggering varied cascade. Finding such a molecule will help for the targeted drug delivery of plumbagin and to improve its efficacy.


 » Conclusion Top


The NCI-H460 cell line successfully imparted tumourigenicity in zebrafish. The efficacy of tumour induction was increased and the mortality of fishes was reduced by using ice-cold anesthesia. The orally administered plumbagin pacified disease condition in zebrafish. The up regulation of p53 gene correlated with the pacifying disease condition of zebrafish. The interaction of plumbagin with the key protein that results in the triggering of signal cascade leading to apoptosis is a scope of further research and it would help in improving the efficacy and reduce the side effects of Plumbagin.


 » Acknowledgments Top


We convey our appreciation to Mr. Benin for his help with the PCR and for the prolonged support. Our thanks to Dr. Valivittan, Dr. Sudhakar and Dr. Sheila for their motivation. We would like to thank Mr. Naresh, Ms. Sona and Ms. Rajarajeshwari for their help. A heartfelt gratitude to Mr. Veeraraghavan for his inspiration

 
 » References Top

1.
Hanahan D, Weinberg RA. The Hallmarks of Cancer. Cell 2000;100:57-70.  Back to cited text no. 1
[PUBMED]    
2.
Boyle P, Levin B, editors. Global Cancer Control. In: World Cancer Report 2008; Lyon: International Agency for Research on Cancer: World Health Organization; 2008. P. 11 -104. Available from: http://www.iarc.fr/en/publications/pdfs-online/wcr/2008/index.php. [Last accessed on 25 Oct 2011].  Back to cited text no. 2
    
3.
Penson DF, Mclerran D, Feng Z, Li L, Albertsen PC, Gilliland FD, et al. 5-year urinary and sexual outcomes after radical prostatectomy: Results from the prostate cancer outcomes study. J Urol 2005;173:1701-5.  Back to cited text no. 3
[PUBMED]    
4.
Nguyen AT, Malonne H, Duez P, Vanhaelen-Fastre R, Vanhaelen M, Fontaine J. Cytotoxic constituents from Plumbago zeylanica. Fitoterapia 2004;75:500-4.  Back to cited text no. 4
[PUBMED]    
5.
Ahmad A, Banerjee S, Wang Z, Kong D, Sarkar FH. Plumbagin-induced apoptosis of human breast cancer cells is mediated by inactivation of NF-κB and Bcl-2. J Cell Biochem 2008;105:1461-71.  Back to cited text no. 5
[PUBMED]    
6.
Thasni KA, Rakesh S, Rojini G, Ratheeshkumar T, Srinivas G, Priya S. Estrogen-dependent cell signaling and apoptosis in BRCA1-blocked BG1 ovarian cancer cells in response to plumbagin and other chemotherapeutic agents. Ann Oncol 2008;19:696-705.  Back to cited text no. 6
[PUBMED]    
7.
Srinivas G, Annab LA, Gopinath G, Banerji A, Srinivas P. Antisense blocking of BRCA1 enhances sensitivity to plumbagin but not tamoxifen in BG-1 ovarian cancer cells. Mol Carcinog 2004;39:15-25.  Back to cited text no. 7
[PUBMED]    
8.
Chen CA, Chang HH, Kao CY, Tsai TH, Chen YJ. Plumbagin, Isolated from Plumbago zeylanica, Induces Cell Death through Apoptosis in Human Pancreatic Cancer Cells. Pancreatology 2009;9:797-809.  Back to cited text no. 8
[PUBMED]    
9.
Gomathinayagam R, Sowmyalakshmi S, Mardhatillah F, Kumar R, Akbarsha MA, Damodaran C. Anticancer Mechanism of Plumbagin, a Natural Compound, on Non-small Cell Lung Cancer Cells. Anticancer Res 2008;28:785-92.  Back to cited text no. 9
[PUBMED]    
10.
Hsu YL, Cho CY, Kuo PL, Huang YT, Lin CC Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Induces Apoptosis and Cell Cycle Arrest in A549 Cells through p53 Accumulation via c-Jun NH2-Terminal Kinase-Mediated Phosphorylation at Serine 15in vitro and in vivo. J Pharmacol Exp Ther 2006;318:484-94.  Back to cited text no. 10
    
11.
Aziz MH, Dreckschmidt NE, Verma AK. Plumbagin, a Medicinal Plant Derived Naphthoquinone, Is a Novel Inhibitor of the Growth and Invasion of Hormone-Refractory Prostate Cancer. Cancer Res 2008;68:9024-32.  Back to cited text no. 11
[PUBMED]    
12.
Powolny AA, Singh SV. Plumbagin-induced Apoptosis in Human Prostate Cancer Cells is Associated with Modulation of Cellular Redox Status and Generation of Reactive Oxygen Species. Pharm Res 2008;25:2171-80.  Back to cited text no. 12
[PUBMED]    
13.
Sandur SK, Ichikawa H, Sethi G, Ahn KS, Aggarwal BB. Plumbagin (5-Hydroxy-2-methyl-1,4-naphthoquinone) Suppresses NF-κB Activation and NF-κB-regulated Gene Products Through Modulation of p65 and Iκκ Kinase Activation, Leading to Potentiation of Apoptosis Induced by Cytokine and Chemotherapeutic Agents. J Biol Chem 2006;281:17023-33.  Back to cited text no. 13
[PUBMED]    
14.
Hawkins WE, Overstreet RM, Fournie JW, Walker WW. Development of aquarium fish models for environmental carcinogenesis: Tumour induction in seven species. J Appl Toxicol 1985;5:261-4.  Back to cited text no. 14
[PUBMED]    
15.
Spitsbergen JM, Tsai HW, Reddy A, Miller T, Arbogast D, Hendricks JD, et al. Neoplasia in Zebrafish (Danio rerio) Treated with 7,12-Diniethylbenz[a] anthracene by Two Exposure Routes at Different Developmental Stages. Toxicol Pathol 2000;28:705-15.  Back to cited text no. 15
[PUBMED]    
16.
Lieschke GJ, Currie PD. Animal models of human disease: Zebrafish swim into view. Nat Rev Genet 2007;8:353-67.  Back to cited text no. 16
[PUBMED]    
17.
Feitsma H, Cuppen E. Zebrafish as a Cancer Model. Mol Cancer Res 2008;6:685-94.  Back to cited text no. 17
[PUBMED]    
18.
Quintana E, Shackleton M, Sabel MS, Fullen DR, Johnson TM, Morrison SJ. Efficient tumour formation by single human melanoma cells. Nature 2008;456:593-8.  Back to cited text no. 18
[PUBMED]    
19.
Banks-Schlegel SP, Gazdar AF, Harris CC. Intermediate Filament and Cross-Linked Envelope Expression in Human Lung Tumour Cell Lines. Cancer Res 1985;45:1187-97.  Back to cited text no. 19
[PUBMED]    
20.
Stoletov K, Montel V, Lester RD, Gonias SL, Klemke R. High-resolution imaging of the dynamic tumour cell-vascular interface in transparent zebrafish. Proc Natl Acad Sci U S A 2007;104:17406-11.  Back to cited text no. 20
[PUBMED]    
21.
Kinkel MD, Eames SC, Philipson LH, Prince VE. Intraperitoneal Injection into Adult Zebrafish. J Vis Exp 2010;42:e2126.  Back to cited text no. 21
    
22.
Knopf F, Schnabel K, Haase C, Pfeifer K, Anastassiadis K, Weidinger G. Dually inducible TetON systems for tissue-specific conditional gene expression in zebrafish. Proc Natl Acad Sci U S A 2010;107:19933-8.  Back to cited text no. 22
[PUBMED]    
23.
Patil CD, Patil SV, Salunke BK, Salunkh RB. Bioefficacy of Plumbago zeylanica (Plumbaginaceae) and Cestrum nocturnum (Solanaceae) plant extracts against Aedes aegypti (Diptera: Culicide) and nontarget fish Poecilia reticulata. Parasitol Res 2010;108:1253-63.  Back to cited text no. 23
    
24.
Chomczynski P, Sacchi N. The single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction: Twenty-something years on. Nat Protoc 2006;1:581-5.  Back to cited text no. 24
[PUBMED]    
25.
Takahashi P, Polson A, Reisman D. Elevated transcription of the p53 gene in early S-phase leads to a rapid DNA-damage response during S-phase of the cell cycle. Apoptosis 2011;16:950-8.  Back to cited text no. 25
[PUBMED]    
26.
White RM, Sessa A, Burke C, Bowman T, LeBlanc J, Ceol C, et al. Transparent Adult Zebrafish as a Tool for In vivo Transplantation Analysis. Cell Stem Cell 2008;2:183-9.  Back to cited text no. 26
[PUBMED]    
27.
Sabaawy HE, Azuma M, Embree LJ, Tsai HJ, Starost MF, Hickstein DD. TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A 2006;103:15166-71.  Back to cited text no. 27
[PUBMED]    
28.
Frazer JK, Meeker ND, Rudner L, Bradley DF, Smith AC, Demarest B, et al. Heritable T-cell malignancy models established in a zebrafish phenotypic screen. Leukemia 2009;23:1825-35.  Back to cited text no. 28
[PUBMED]    
29.
Hill JV, Davison W, Forster ME. The effects of fish anaesthetics (MS222, metomidate and AQUI-S) on heart ventricle, the cardiac vagus and branchial vessels from Chinook salmon (Oncorhynchus tshawytscha). Fish Physiol Biochem 2002;27:19-28.  Back to cited text no. 29
    
30.
Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nat Rev Cancer 2003;3:768-80.  Back to cited text no. 30
[PUBMED]    
31.
Premakumari P, Rathinam K, Santhakumari G. Anti fertility activity of Plumbagin. Indian J Med Res 1997;829-38.  Back to cited text no. 31
    
32.
Kalyani R, Das S, Kumar ML. Pattern of cancer in adolescent and young adults--a ten year study in India. Asian Pac J Cancer Prev 2010;11:655-9.  Back to cited text no. 32
[PUBMED]    
33.
Lane DP. p53, guardian of the genome. Nature 1992;358:15-6.  Back to cited text no. 33
[PUBMED]    
34.
Milner J. A Conformation Hypothesis for the Suppressor and Promoter Functions of p53 in Cell Growth Control and in Cancer. Proc Biol Sci 1991;245:139-45.  Back to cited text no. 34
[PUBMED]    
35.
Levine AJ, Momand J, Finlay CA. The p53 tumour suppressor gene. Nature 1991;351:453-6.  Back to cited text no. 35
[PUBMED]    
36.
Kawamura T, Suzuki J, Wang YV, Menendez S, Morera LB, Raya A, et al. Linking the p53 tumour suppressor pathway to somatic cell reprogramming. Nature 2009;460:1140-4.  Back to cited text no. 36
[PUBMED]    
37.
Shay JW, Pereira-Smith OM, Wright WE. A role for both RB and p53 in the regulation of human cellular senescence. Exp Cell Res 1991;196:33-9.  Back to cited text no. 37
[PUBMED]    
38.
Tishler RB, Lamppu DM, Park S, Price BD. Microtubule-active Drugs Taxol, Vinblastine, and Nocodazole Increase the Levels of Transcriptionally Active p53. Cancer Res 1995;55:6021-5.  Back to cited text no. 38
[PUBMED]    
39.
Chow J, Norng M, Zhang J, Chai J. TRPV6 mediates capsaicin-induced apoptosis in gastric cancer cells Mechanisms behind a possible new “hot” cancer treatment. Biochim Biophys Acta 2007;1773:565-76.  Back to cited text no. 39
[PUBMED]    
40.
Jee SH, Shen SC, Tseng CR, Chiu HC, Kuo ML. Curcumin Induces a p53-Dependent Apoptosis in Human Basal Cell Carcinoma Cells. J Invest Dermatol 1998;111:656-1.  Back to cited text no. 40
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

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