Hesperidin Increases Cytotoxic Effect of 5-Fluorouracil on WiDr Cells

Yurista Gilang, Adam Hermawan, Aditya Fitriasari, Riris Istighfari Jenie

Abstract


Therapy of colon cancer by using 5-FU often causes problems of resistance. This encourages the development of co-chemotherapy agent. One of the compounds that could potentially be used as a co-chemotherapy agent is hesperidin. This study was conducted to determine the cytotoxic effects of hesperidin, 5-FU and the combination of them, as well as apoptosis induction in colon cancer cells WiDr. Cytotoxic effect of hesperidin, 5-FU, and its combination were observed using MTT assay. Observation of apoptosis was done by double staining method using ethidium bromide-acridin orange. Until 48 hours incubation, hesperidin showed no cytotoxic effects. Cytotoxic effects of 5-FU was observed after 48 hours with the IC50 value of 422 µM. However, hesperidin improved the cytotoxic effects of 5-FU at 48 hour incubation. Either single treatment of hesperidin 200µM or 5-FU 1500 µM did not trigger apoptosis, but combination of them led to the emergence of signs of apoptosis. Based on this study,it can be concluded thathesperidin is potential to be developed as a co-chemotherapy agent of 5-FU on colon cancer but still need further study on its molecular mechanisms.

Keywords : hesperidin, 5-fluorouracil, WiDr cells, cytotoxic, apoptosis


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References


Callaghan, R., Stafford, A. and Epand, R.M., 1993, Increased Accumulation of Drugs in A Multidrug Resistant Cell Line by Alteration of Membrane Biophysical Properties, Biochim. Biophys. Acta., 1175(3), 277-282. Link

Center, M.M., Jemal, A., Smith, R.A. and Ward, E., 2009, Worldwide Variations in Colorectal Cancer, CA Cancer J. Clin., 59, 366-378. CrossRef

El-Readi, M.Z., Hamdan, D., Farrag, N., El-Shazly, A. and Wink, M., 2009, Inhibition of P-glycoprotein Activity by Limonin and Other Secondary Metabolites from Citrus Species in Human Colon and Leukaemia Cell Lines, Eur. J. Pharmacol., 626, 139-145. CrossRef

Lee, C.J., Wilson, L., Jordan, M.A., Nguyen, V., Tang, J. and Smiyun, G., 2009, Hesperidin Suppressed Proliferations of Both Human Breast Cancer and Androgen-dependent Prostate Cancer Cells, Phytother. Res., 24, 15-19. CrossRef

Liu, H.C., Chen, G.G., Vlantis, A.C., Leung, B.C.S., Tong, M.C.E. and van Hasselt, C.A., 2006, 5-Fluorouracil Mediates Apoptosis and G1/S Arrest in Laryngeal Squamous Cell Carcinoma via a p53-Independent Pathway, Cancer J., 12(6), 482-493. Link

Matuo, R., Sousa, F.G., Escargueil, A.E., Grivicich, I., Garcia-Santos, D., Chies, J.A., et al., 2008, 5-Fluorouracil and Its Active Metabolite FdUMP Cause DNA Damage in Human SW620 Colon Adenocarcinoma Cell Line, J. Appl. Toxicol., 29(4), 308-316. CrossRef

Meyerhardt, J.A. and Mayer, R.J., 2005, Systemic Therapy for Colorectal Cancer, N. Engl. J. Med., 352(5), 476-487. CrossRef

Park, H.J., Kim, M.J., Ha, E. and Chung, J.H., 2008, Apoptotic Effect of Hesperidin Through Caspase3 Activation in Human Colon Cancer Cells, SNU-C4, Phytomedicine, 15(1-2), 147-151. CrossRef

Priestman, T., 2008, Cancer Chemotherapy In Clinical Practice, Springer, London, 96-98.

Rekam Medis RSKD, 2009, Statistik Kanker : 10 Besar Kanker Tersering RSKD RawatJalan (KasusBaru) tahun 2007, Website, http://www.dharmais.co.id/index.php/cance-statistic.html, accessed on March 2010. Link

Ruddon, R.W., 2007, Cancer Biology, 4th Edition., New York: Oxford University Press.

Violette, S., Poulain, L., Dussaulx, E., Pepin, D., Faussat, A.M., Chambaz, J., et al., 2002, Resistance of Colon Cancer Cells to Long-term 5-fluorouracil Exposure is Correlated to the Relative Level of Bcl-2 and Bcl-X(L) in Addition to Bax and p53 Status, Int. J. Cancer, 98(4), 498-504. Link

Voboril., R., Hochwald, S.N., Li, J., Brank. A., Wessels, F., Moldawer, L.L., et al., 2004, Inhibition of NF-kappa B Augments Sensitivity to 5-fluorouracil/Folinic Acid in Colon Cancer, J. Surg. Res., 120(2), 178-188. CrossRef

Wang, W., McLeod, H. and Cassidy, J., 2003, Disulfiram-mediated Inhibition of NF-kappaB Activity Enhances Cytotoxicity of 5-Fluorouracil in Human Colorectal Cancer Cell Lines, Intl. J. Cancer., 104(4), 504-511. CrossRef




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev3iss2pp404-409

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