Resveratrol Triggers Apoptosis In Colon Cancer Cells Rather Than Senescence

Main Article Content

Servet Madencioğlu
Eda Becer
Hilal Kabadayı
Hafize Seda Vatansever
Sevinç Yücecan

Keywords

Keywords: Resveratrol, cell death, Colo-320, Colo-741

Abstract

Objective: Resveratrol is a phenolic compound that classified in stilbenoid and used as anticancer agent in many cancer types. The purpose of the study is to determine apoptotic and senescence inducing effects in primary (Colo-320) and metastatic (Colo-741) colon cancer cells.


Methods: Cell growth and cytotoxicity were detected by MTT method in both Colo-320 and Colo-741 cell lines. Apoptotic and senescence inducing activities were tested with TUNEL staining, X-gal staining and immunocytochemistry using antibodies directed against to Bax, Bcl-2, caspase-3, Hsp27, Lamin B1, p16, cyclin B1.


Results: According to MTT results, 25 μg/mL and 10 μg/mL concentrations of resveratrol were found more effective for Colo-320 and Colo-741 cell lines, respectively. As a result of immunocytochemical staining, Bax immunoreactivity was significantly increased while Bcl-2 immunoreactivity significantly decreased in Colo-320 cell line. Increased Hsp27, lamin B1 and p16 immunoreactivities on Colo-320 cells were not significant. In Colo-741 cells, Bcl-2 immunoreactivity was significantly increased. Hsp27 immunoreactivity in Colo-320 cell line was significantly higher than Colo-741 cell line. In addition, after resveratrol administration, while the TUNEL positive cells significantly increased in Colo-320 cells, X-gal positive cells was detected in Colo-741 than Colo-320 cells.


Conclusion: Resveratrol can inhibit cell viability both in primer and metastatic colon cancer cells. However, resveratrol might be more effective triggering mitochondrial-mediated apoptosis in primary colon cancer cells. Apoptotic and cell cycle inhibiting effects of resveratrol may differ by cell type. Therefore, resveratrol may be a potential phytotherapeutic agent for colon cancer according to the cell origin.

Abstract 961 | PDF Downloads 293

References

1. WHO. Cancer facts&Figures 2017-2019. https://www.who.int/news-room/fact-sheets/detail/cancer date the access: 30.09.2019.
2. WHO. IARC handbooks of cancer prevention. Colorectal Cancer Screening. Lyon Cedex 08, France. 2019.
3. Sales MJ., Resurreccion AVA. Resveratrol in peanuts. Crıt Rev Food Sci 2014;54: 734-70.
4. Park JE., Pezzuto MJ. The pharmacology of resveratrol in animals and humans. Biochimia Et Biophysica Acta 2015; 1852: 1071-13.
5. Alberts B., Johnson A., Lewis J., Morgan D., Raff M., Roberts K. et al. Molecular biology of the cell 6th Ed. New York: Garland Science, Taylor&Francis, 2015.
6. Miki H., Uehara N., Kimura A., Sasaki T., Yuri T., Yoshizawa K., et al. Resveratrol induces apoptosis via ROS-triggered autophagy in human colon cancer cells. Int J Oncol 2012; 40: 1020-1028.
7. El-Readi MZ, Eid SY, Abdelghany AA, Al-Amoudi HS, Efferth T, Wink M. Resveratrol mediated cancer cell apoptosis, and modulation of multidrug resistance proteins and metabolic enzymes. Phytomedicine 2019; 55: 269-81.
8. Radhakrishnan S., Reddivari L., Sclafani R., Das UN., Vanamala J. Resveratrol potentiates grape seed extract induced human colon cancer. Cell Apoptosis. Front Biosci (Elite Ed) 2011; 1: 1509-23.
9. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35: 495-516.
10. Gonzalez LC., Ghadaouia S., Martinez A., Rodier F. Premature aging/senescence in cancer cells facing therapy: good or bad? Biogerontology 2016; 17: 71-87.
11. Lukášová E., Kovařík A., Kozubek S. Consequences of lamin B1 and lamin B receptor downregulation in senescence. Cells 2018; 7: 11-9.
12. Colin DJ., Limagne K., Lizard G., Ghiringhelli F., Solary E., et al. The role of reactive oxygen species and subsequent DNA-damage response in the emergence of resistance towards resveratrol in colon cancer models. Cell Death Dis 2014; 5: 1533-45.
13. Mikuła-Pietrasik J., Niklas A., Uruski P., Tykarski A., Książek K. Mechanisms and significance of therapy-induced and spontaneous senescence of cancer cells. Cell. Mol 2019; 14: 1-7.
14. O'callaghan-Sunol C., Gabai VL, Sherman M.Y. Hsp27 modulates p53 signalling and suppresses cellular senescence. Cancer Res 2007; 67: 11779-88.
15. Farhadnejad H., Emamat H., Zand H. The Effect of Resveratrol on Cellular Senescence in Normal and Cancer Cells: Focusing on Cancer and Age-Related Diseases. Nutr Cancer 2019; 71: 1175-80.
16. Jiang Z., Chen K., Cheng L., Yan B., Qian W., Cao J., Li J., Wu E., Ma Q., Yang W. Resveratrol and cancer treatment: updates. Ann. N. Y. Acad. Sci 2017; 1403: 59-9.
17. Kim CW., Hwang KA., Choi KC. Anti-Metastatic potential of resveratrol and its metabolites by the inhibition of epithelial-mesenchymal transition, migration, and invasion of malignant cancer cells. Phytomedicine 2016; 23: 1787-96.
18. Elshaer M., Chen Y., Wang XJ., Tang X. Resveratrol: an overview of its anti-cancer mechanisms. Life Sci 2018; 207: 340-49.
19. Wang X., Wang D., Zhao Y. Effect and mechanism of resveratrol on the apoptosis of lung adenocarcinoma cell line A549. Cell Bıochem Bıophys 2015; 73: 527-31.
20. Chen J., Dong XS., Guo XG. Inhibitory effect of resveratrol on the growth of human colon cancer ls174t cells and its subcutaneously transplanted tumor in nude mice and the mechanism of action. Zhonghua Zhong Liu Za Zhi [Chinese Journal Of Oncology] 2009; 31: 15-9.
21. Baek SH., Ko JH., Lee H., Jung J., Kong M., Lee JW., Lee J., Chinnathambi A., Zayed ME., Alharbi SA., Lee SG. Resveratrol inhibits STAT3 signaling pathway through the induction of SOCS-1: Role in apoptosis induction and radiosensitization in head and neck tumor cells. Phytomedicine 2016; 23: 566-77.
22. Pistritto G., Trisciuoglio D., Ceci C., Garufi A., D’orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging 2016; 8: 603-19.
23. Chen H., Jin ZL., Xu H. MEK/ERK signalling pathway in apoptosis of SW620 cell line and inhibition effect of resveratrol. Asian Pac. J. Trop. Med 2016; 9: 49-53.
24. Ji S., Zheng Z., Liu S., Ren G., Gao J., Zhang Y., Li G. Resveratrol promotes oxidative stress to drive dlc1 mediated cellular senescence in cancer cells. Exp Cell Res 2018; 370: 292-302.
25. Giménez‐Bastida JA., Ávila‐Gálvez MA., Espín JC., González‐Sarrías A. Conjugated physiological resveratrol metabolites induce senescence in breast cancer cells: role of p53/p21 and p16/Rb pathways, and abc transporters. Mol. Nutr. Food Res 2019; 63: 1900629.
26. Díaz-Chávez J., Fonseca-Sánchez MA., Arechaga-Ocampo E., Flores-Pérez A., Palacios-Rodríguez Y., Domínguez-Gómez G., Marchat LA., Fuentes-Mera L., Mendoza-Hernández G., Gariglio P., López-Camarillo C. Proteomic profiling reveals that resveratrol inhibits Hsp27 expression and sensitizes breast cancer cells to doxorubicin therapy. Plos One 2013; 8: 64378.
27. Wei MC., Zong WX., Cheng EH., Lindsten T., Panoutsakopoulou V., Ross AJ., Roth KA., MacGregor GR., Thompson CB., Korsmeyer SJ. Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science 2001; 292: 727-30.
28. Li P., Nijhawan D., Budihardjo I., Srinivasula SM., Ahmad M., Alnemri ES., Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 1997; 9: 479-89.
29. Acunzo J., Katsogiannou M., Rocchi P. Small heat shock proteins HSP27 (HspB1), αB-crystallin (HspB5) and HSP22 (HspB8) as regulators of cell death. The international journal of biochemistry & cell biology 2012; 44: 1622-31.
30. Cilibrasi C., Riva G., Romano G., Cadamuro M., Bazzoni R., Butta V., Paoletta L., Dalpra L., Strazzabosco M., Lavitrano M., Giovannoni R. Resveratrol impairs glioma stem cells proliferation and motility by modulating the wnt signaling pathway. PLoS One 2017; 12: e0169854
31. Hoca M., Becer E., Kabadayı H., Yücecan S., Vatansever HS. The effect of resveratrol and quercetin on epithelial-mesenchymal transition in pancreatic cancer stem cell. Nutr Cancer 2019; 8: 1-2.
32. Paul C., Manero F., Gonin S., Kretz-Remy C., Virot S., Arrigo A.P. Hsp27 as a negative regulator of cytochrome C release. Molecular and Cellular Biology 2002; 22: 816-34.
33. Sakthivel KM., Sehgal P. A novel role of lamins from genetic disease to cancer biomarkers. Oncol Rev 2016; 10: 309.
34. Izdebska M., Gagat M., Grzanka A. Overexpression of lamin b1 induces mitotic catastrophe in colon cancer Lovo cells and is associated with worse clinical outcomes. Int J Oncol 2018; 52: 89-102

35. Malvezzi H., Viana BG., Dobo C., Filippi RZ., Podgaec S., Piccinato CA. Depleted lamin B1: a possible marker of the involvement of senescence in endometriosis? Arch Gynecol Obstet 2018; 297: 977-84.
36. Liu L., Wang J., Shi L., Zhang W., Du X., Wang Z., Zhang Y. β-asarone induces senescence in colorectal cancer cells by inducing lamin B1 expression. Phytomedicine 2013; 20: 512-520.
37. Yamashiro Y., Sasaki H., Ibaraki N., Nagai K., Kawakami Y., Yaguchi H., Fujita N., Osada H., Sasaki K. Cyclin-dependent kinase inhibitor p16 and p21 expression, and cell cycle change in human lens epithelial cell line SRA 01/04 following contact inhibition in normal culture. Ophthalmic Res 2011; 46: 38-43.
38. Ye C., Wang J., Wu P., Li X., Chai Y. Prognostic role of cyclin B1 in solid tumours: a meta-analysis. Oncotarget 2017; 8: 2224-2232.
39. Zhang H., Zhang X., Li X., Meng WB., Bai ZT., Rui SZ., Wang ZF., Zhou WC., Jin XD. Effect of Ccnb1 silencing on cell cycle, senescence, and apoptosis through the p53 signalling pathway in pancreatic cancer. J Cell Physiol 2019; 234: 619-31.

Most read articles by the same author(s)