The Cytotoxic Effects of 5FU on Hek293 and HeLa Cells in vitro

Document Type : Original paper


1 Department of Biology, Faculty of Basic Sciences, Hamedan Branch, Islamic Azad University, Hamedan, Iran

2 Department of Biology, Faculty of Advanced Sciences and Technologies, Tehran Medical Branch, Islamic Azad University, Tehran, Iran

3 Department of Biology, Avicenna International College, Budapest, Hungary


Background and aim: 5-Fluorouracil (5FU) is one of the most commonly used drugs in chemotherapy for cancer treatment. In combination with other cancer drugs, it is used to treat many types of cancer including breast, colon, stomach and cervix cancer. However, treatment with 5FU is followed by serious side effects on healthy non-cancerous cells. The aim of this study was to investigate the cytotoxic effects of 5FU on cervical cancer (Hela) cells compared to non-cancerous (Hek293) cells. Materials and methods: In this experimental-laboratory study, HeLa and Hek293 cells were divided into control group (no- treated) and groups treated with 3.90625, 7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml of 5FU. MTT assay method was used to evaluate the cell viability. Results: The findings showed that 3.90625, 7.8125 and 15.625 µg/ml of 5FU did not significantly change cell viability, however, 31.25, 62.5, 125, 250 and 500 µg/ml of 5FU significantly decreased the Hek293 cell viability. Treatment of HeLa cells with 3.90625 and 7.8125 µg/ml of 5FU did not significantly change the cell viability, while HeLa cells treated with 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml of 5FU showed a significant decrease in cell viability. Conclusion: In conclusion, high doses of 5FU has the same cytotoxic effects on HeLa and Hek293 cells, however, there was a narrow difference between 5FU cytotoxic effects on HeLa cancer cells compared to non-cancerous in lower doses indicating that 5FU concentration play a significant role in its cytotoxic action on healthy cells.


[1]. Hull R, Mbele M, Makhafola T, Hicks C, Wang SM, Reis RM, Mehrotra R, Mkhize‑Kwitshana Z, Kibiki G, Bates DO, Dlamini Z. Cervical cancer in low and middle‑income countries. Oncology letters. 2020;20(3):2058-74.
[2]. Sharma S, Deep A, Sharma AK. Current treatment for cervical cancer: an update. Anti-Cancer
Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2020;20(15):1768-79.
[3]. Saphner T, Gallion HH, van Nagell JR, Kryscio R, Patchell RA. Neurologic complications of
cervical cancer. A review of 2261 cases. Cancer. 1989;64(5):1147-51.
[4]. Wang YQ, Lu JL, Liang YR, Li QS. Suppressive effects of EGCG on cervical cancer.
Molecules. 2018;23(9):2334.
[5]. Ordikhani F, Erdem Arslan M, Marcelo R, Sahin I, Grigsby P, Schwarz JK, Azab AK. Drug
delivery approaches for the treatment of cervical cancer. Pharmaceutics. 2016;8(3):23.
[6]. Liang C, Liu P, Cui Z, Liang Z, Bin X, Lang J, Chen C. Effect of laparoscopic versus abdominal radical hysterectomy on major surgical complications in women with stage IA-IIB cervical cancer in China, 2004–2015. Gynecologic oncology. 2020;156(1):115-23.
[7]. Chaichian S, Moazzami B, Sadoughi F, Haddad Kashani H, Zaroudi M, Asemi Z. Functional activities of beta-glucans in the prevention or treatment of cervical cancer. Journal of Ovarian Research. 2020;13(1):1-12.
[8]. Shafabakhsh R, Reiter RJ, Mirzaei H, Teymoordash SN, Asemi Z. Melatonin: a new inhibitor agent for cervical cancer treatment. Journal of cellular physiology. 2019;234(12):21670-82.
[9]. Pariente R, Pariente JA, Rodríguez AB, Espino J. Melatonin sensitizes human cervical cancer HeLa cells to cisplatin‐induced cytotoxicity and apoptosis: effects on oxidative stress and DNA fragmentation. Journal of pineal research. 2016;60(1):55-64.
[10]. Šarenac T, Mikov M. Cervical cancer, different treatments and importance of bile acids as
therapeutic agents in this disease. Frontiers in Pharmacology. 2019;10:484.
[11]. Miura K, Kinouchi M, Ishida K, Fujibuchi W, Naitoh T, Ogawa H, Ando T, Yazaki N, Watanabe K, Haneda S, Shibata C. 5-fu metabolism in cancer and orally-administrable 5-fu drugs. Cancers. 2010;2(3):1717-30.
[12]. Cho YH, Ro EJ, Yoon JS, Mizutani T, Kang DW, Park JC, Il Kim T, Clevers H, Choi KY. 5-FU promotes stemness of colorectal cancer via p53-mediated WNT/β-catenin pathway activation. Nature communications. 2020;11(1):1-3.
[13]. Shehatta NH, Okda TM, Omran GA, Abd-Alhaseeb MM. Baicalin; a promising chemopreventive agent, enhances the antitumor effect of 5-FU against breast cancer and inhibits tumor growth and angiogenesis in Ehrlich solid tumor. Biomedicine & Pharmacotherapy. 2022;146:112599.
[14]. Peters GJ, Van der Wilt CL, Van Moorsel CJ, Kroep JR, Bergman AM, Ackland SP. Basis for effective combination cancer chemotherapy with antimetabolites. Pharmacology & therapeutics. 2000;87(2-3):227-53.
[15]. Mazevet M, Moulin M, Llach-Martinez A, Chargari C, Deutsch É, Gomez AM, Morel É. Complications of chemotherapy, a basic science update. La Presse Médicale. 2013;42(9):e352-61.
[16]. Kim YJ, Jeong J, Sohn KY, Lee DY, Yoon SY, Kim JW. Therapeutic potential of EC-18 as a chemotherapy adjuvant for 5-fluorouracil-induced neutropenia. Cancer Research. 2019;79(13_Supplement):360.
[17]. Naren G, Guo J, Bai Q, Fan N, Nashun B. Reproductive and developmental toxicities of 5-fluorouracil in model organisms and humans. Expert Reviews in Molecular Medicine. 2022;24.
[18]. Al-Asmari AK, Al-Zahrani AM, Khan AQ, Al-Shahrani HM, Ali Al Amri M. Taurine ameliorates 5-flourouracil-induced intestinal mucositis, hepatorenal and reproductive organ damage in Wistar rats: A biochemical and histological study. Human & experimental toxicology.2016;35(1):10-20.
[19]. Mavrikou S, Tsekouras V, Karageorgou MA, Moschopoulou G, Kintzios S. Detection of superoxide alterations induced by 5-fluorouracil on HeLa cells with a cell-based biosensor. Biosensors. 2019;9(4):126.
[20]. D‘souza UJ. Toxic effects of 5-fluorouracil on sperm count in wistar rats. The Malaysian journal of medical sciences: MJMS. 2003;10(1):43
Volume 1, Issue 3
(Special Issue: papers selected from ICLS22, Istanbul, Turkey)
Pages 128-133
  • Receive Date: 04 October 2022
  • Revise Date: 08 October 2022
  • Accept Date: 15 October 2022