Zingiber Officinale Var. Rubrum Extract Increases The Cytotoxic Activity Of 5-Fluorouracil In Colon Adenocarcinoma Widr Cells
Keywords:
red ginger, 5-Fluorouracil, WiDr cell lines, cochemotherapy, cytotoxic effect
Abstract
One of the main chemotherapy agents for colon cancer is 5-fluorouracil (5-FU). However, the effectiveness of 5-FU decreased; therefore, co-chemotherapy with another agent is needed to enhance the activity. This study aims to determine the effect of red ginger extract as a co-chemotherapy agent with 5-FU on WiDr colon adenocarcinoma cells. We investigated the cytotoxic activity of the ethanolic extract of rhizome red ginger and combination with 5-fluorouracil (5-FU) in WiDr human colorectal cancer cell line. Red ginger extract was extracted by using 96% ethanol. Cytotoxic assay of red ginger extract and 5-FU was performed using MTT assay for 24 and 48 hours. Treatment of 5-FU in WiDr cells for 48 hours showed an IC50 value of 130 µg/mL, while no IC50 value was obtained for the 24 hours treatment. Treatment of red ginger extract with an incubation time of 24 and 48 hours had a cytotoxic effect on WiDr cells with IC50 values of 68 µg/mL and 65 µg/mL, respectively. The combination of 1000 μg/mL 5-fluorouracil with 35 μg/mL red ginger extract at 24-hour incubation resulted in a smaller cell viability value than every single treatment. The combination treatment of 5-FU 60 μg/mL with red ginger extract at a 25 μg/mL concentration causes a more significant decrease in cell viability than a single 5-FU treatment. In conclusion, red ginger extract may increase the cytotoxic activity of 5-FU in colon adenocarcinoma WiDr cells.
References
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Sang S, Hong J, Wu H, Liu J, Yang CS, Pan MH, dkk. Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols. J Agric Food Chem. 2009.57(22):10645-50. https://doi.org/10.1021/jf9027443
Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA. Combined ginger extract and Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells. Nutr J. 2015.14:31. https://doi.org/10.1186/s12937-015-0015-2
Wahyuni S, Xu DH, Bermawie N, Tsunematsu H, Ban T, Genetic relationships among ginger accessions based on AFLP marker, Jurnal Bioteknologi Pertanian, 2003. 8(2): 60-68
Wu JJ, Omar HA, Lee YR, Teng YN, Chen PS, Chen YC, dkk. 6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms. Eur J Pharmacol. 2015.762:449-458. https://doi.org/10.1016/j.ejphar.2015.06.032
Zhang N, Yin Y, Xu SJ, Chen WS, 5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies. Molecules. 2008.13:1551-96. https://doi.org/10.3390/molecules13081551
Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer. 2013.132(5):1133-45. https://doi.org/10.1002/ijc.27711
Ekowati H, Achmad A, Nurrachmani EP, Wasito H, Sri K, Hidayati Z, dkk. Zingiber officinale, Piper retrofractum and Combination Induced Apoptosis and p53 Expression in Myeloma and WiDr Cell Lines. Hayati Journal of Biosciences. 2012.19(3):137-40. https://doi.org/10.4308/hjb.19.3.137
Elkady AI, Hussein RA, Abu-Zinadah OA. Differential control of growth, apoptotic activity and gene expression in human colon cancer cells by extracts derived from medicinal herbs, Rhazya stricta and Zingiber officinale and their combination. World J Gastroenterol. 2014.20(41):15275-88. https://doi.org/10.3748/wjg.v20.i41.15275
Fan J, Yang X, Bi Z. 6-Gingerol inhibits osteosarcoma cell proliferation through apoptosis and AMPK activation. Tumour Biol. 2015.36(2):1135-41. https://doi.org/10.1007/s13277-014-2723-1
Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941-53. https://doi.org/10.1002/ijc.31937.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, dkk. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015.136(5):E359-86.
Giovannetti E, Backus HHJ, Wouters D, Ferreira CG, van Houten VMM, Brakenhoff dkk. Changes in the Status of p53 Affect Drug Sensitivity to Thymidylate Synthase (TS) Inhibitors by Altering TS Levels, Br J Can. 2007.96:769-75. https://doi.org/10.1038/sj.bjc.6603639
Hakim L, Alias E, Makpol S, Ngah WZ, Morad NA, Yusof YA. Gelam honey and ginger potentiate the anti cancer effect of 5-FU against HCT 116 colorectal cancer cells. Asian Pac J Cancer Prev. 2014.15(11):4651-7. https://doi.org/10.7314/APJCP.2014.15.11.4651
Han MA, Woo SM, Min KJ, Kim S, Park JW, Kim DE, dkk. 6-Shogaol enhances renal carcinoma Caki cells to TRAIL-induced apoptosis through reactive oxygen species-mediated cytochrome c release and down-regulation of c-FLIP(L) expression. Chem Biol Interact. 2015.228:69-78. https://doi.org/10.1016/j.cbi.2015.01.020
Hsu YL, Hung JY, Tsai YM, Tsai EM, Huang MS, Hou MF, dkk. 6-shogaol, an active constituent of dietary ginger, impairs cancer development and lung metastasis by inhibiting the secretion of CC-chemokine ligand 2 (CCL2) in tumor-associated dendritic cells. J Agric Food Chem. 2015.63(6):1730-8. https://doi.org/10.1021/jf504934m
Hwang JS, Lee HC, Oh SC, Lee DH, Kwon KH. Shogaol overcomes TRAIL resistance in colon cancer cells via inhibiting of survivin. Tumour Biol. 2015. Jun 11:1-11. https://doi.org/10.1007/s13277-015-3629-2
Kim MO, Lee MH, Oi N, Kim SH, Bae KB, Huang Z, dkk. [6]-shogaol inhibits growth and induces apoptosis of non-small cell lung cancer cells by directly regulating Akt1/2. Carcinogenesis. 2014.35(3):683-91. https://doi.org/10.1093/carcin/bgt365
Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003.3(5):330-8. https://doi.org/10.1038/nrc1074
Meyerhardt JA, Mayer RJ. Systemic Therapy for Colorectal Cancer. N. Engl. J. Med. 2005.352(5): 476-487. https://doi.org/10.1056/NEJMra040958
Nur KA, Putri H, Cahyani FM, Katarina A, Susidarti RA, Meiyanto E. Ethanolic extract of Moringa oleifera L., Increases Sensitivity of WiDr colon cancer line towards 5-Fluorouracil. Indonesian Journal of Cancer Chemoprevention. 2011.1(2):124-8. http://dx.doi.org/10.14499/indonesianjcanchemoprev1iss2pp124-128
Nurulita NA, Meiyanto E, Sugiyanto, Matsuda E, Kawaichi M. The Ethyl Acetate Fraction of Gynura procumbens Sensitizes WiDr Colon Cancer Cell Line Against 5-Fluorouracil But Shows Antagonism With Cisplatin. International Journal of Phytomedicine. 2011.3(3):392-405.
Pan MH, Hsieh MC, Kuo JM, Lai CS, Wu H, Sang S, dkk. 6-Shogaol induces apoptosis in human colorectal carcinoma cells via ROS production, caspase activation, and GADD 153 expression. Mol Nutr Food Res. 2008.52(5):527-37. https://doi.org/10.1002/mnfr.200700157
Prasad S, Tyagi AK. Ginger and its constituents: role in prevention and treatment of gastrointestinal cancer. Gastroenterol Res Pract. 2015.2015:142979. https://doi.org/10.1155/2015/142979
Qi LW, Zhang Z, Zhang CF, Anderson S, Liu Q, Yuan CS, dkk. Anti-Colon Cancer Effects of 6-Shogaol Through G2/M Cell Cycle Arrest by p53/p21-cdc2/cdc25A Crosstalk. Am J Chin Med. 2015:1-14. https://doi.org/10.1142/S0192415X15500469
Radhakrishnan EK, Bava SV, Narayanan SS, Nath LR, Thulasidasan AK, Soniya EV, dkk. [6]-Gingerol induces caspase-dependent apoptosis and prevents PMA-induced proliferation in colon cancer cells by inhibiting MAPK/AP-1 signaling. PLoS One. 2014.9(8):e104401. https://doi.org/10.1371/journal.pone.0104401
Rodrigues NR, Rowan A, Smith ME, Kerr IB, Bodmer WF, Gannon JV, dkk. p53 mutations in colorectal cancer. Proc Natl Acad Sci USA. 1990. 87(19):7555-9. https://doi.org/10.1073/pnas.87.19.7555
Saif MW, Choma A, Salamone SJ, Chu E. Pharmacokinetically guided dose adjustment of 5-fluorouracil: a rational approach to improving therapeutic outcomes. J Natl Cancer Inst. 2009. 101(22):1543-52. https://doi.org/10.1093/jnci/djp328
Sang S, Hong J, Wu H, Liu J, Yang CS, Pan MH, dkk. Increased growth inhibitory effects on human cancer cells and anti-inflammatory potency of shogaols from Zingiber officinale relative to gingerols. J Agric Food Chem. 2009.57(22):10645-50. https://doi.org/10.1021/jf9027443
Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA. Combined ginger extract and Gelam honey modulate Ras/ERK and PI3K/AKT pathway genes in colon cancer HT29 cells. Nutr J. 2015.14:31. https://doi.org/10.1186/s12937-015-0015-2
Wahyuni S, Xu DH, Bermawie N, Tsunematsu H, Ban T, Genetic relationships among ginger accessions based on AFLP marker, Jurnal Bioteknologi Pertanian, 2003. 8(2): 60-68
Wu JJ, Omar HA, Lee YR, Teng YN, Chen PS, Chen YC, dkk. 6-Shogaol induces cell cycle arrest and apoptosis in human hepatoma cells through pleiotropic mechanisms. Eur J Pharmacol. 2015.762:449-458. https://doi.org/10.1016/j.ejphar.2015.06.032
Zhang N, Yin Y, Xu SJ, Chen WS, 5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies. Molecules. 2008.13:1551-96. https://doi.org/10.3390/molecules13081551
Published
2020-12-29
How to Cite
Sarmoko, S., Solihati, I., Setyono, J., Ekowati, H., & Fadlan, A. (2020). Zingiber Officinale Var. Rubrum Extract Increases The Cytotoxic Activity Of 5-Fluorouracil In Colon Adenocarcinoma Widr Cells . Indonesian Journal of Pharmacy, 31(4), 266-272. https://doi.org/10.22146/ijp.859
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Research Article
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