Investigation of the Apoptotic Effect of Levofloxacin on Ovarian Follicles of NMRI Mice and its Anticancer Effect on Human Ovarian Cancer Cell Line


Keywords: levofloxacin, apoptosis, ovary, ovarian cancer, Bax, Bcl-2, Caspase-3


How to Cite

Borhani, S. S. ., Hayati Roodbari, N., Heidarieh, N. ., & Roshanaei, K. . (2022). Investigation of the Apoptotic Effect of Levofloxacin on Ovarian Follicles of NMRI Mice and its Anticancer Effect on Human Ovarian Cancer Cell Line. Iranian Red Crescent Medical Journal, 24(7). Retrieved from


Background:Levofloxacin is a fluoroquinolone antibiotic with extensive anti-bacterial effects.

Objectives: This research surveyed the cytotoxicity effects of levofloxacin on ovarian follicles of mice in both in vitro and in vivo conditions, as well as its anticancer effect on human ovarian cancer cell line (SKOV3).

Methods: For in vitro study, the ovaries of animals were isolated and treated with levofloxacin at doses of 1, 2, 5, and 10 µg/ml for 6 days. For in vivo study, animals were treated with levofloxacin at concentrations of 100, 200, 400, and 800 mg/kg for 24 days. Histopathological and morphological examinations of ovarian tissues were performed. Real-time PCR and Western Blot techniques were performed to analyze apoptosis-related genes and proteins of ovarian tissues.

Results: Levofloxacin at higher concentrations caused morphological changes and remarkably decreased the number of primary, secondary, and adult follicles compared to the control group. The percentage of viable SKOV3 cells was 10.12%, 7.63%, and 2.17% following exposure to levofloxacin (at a concentration of 800 μg/ml) for 24, 48, and 72 h, respectively. The half-maximal inhibitory concentration of levofloxacin against SKOV3 was found to be 181.1, 74.84, and 27.58 μg/ml at 24, 48, and 72 h, respectively. The percentage of SKOV3 cells apoptosis following exposure to levofloxacin after 72 h at 20, 80, and 200 μg/ml doses was 11%, 42%, and 52%, respectively. Real-time PCR revealed up-regulation of Bax and Caspase-3 genes after exposure to levofloxacin in SKOV3 cells, whereas the expression of Bcl2 was significantly decreased in a concentration-depended manner.

Conclusion: The present study demonstrates that levofloxacin induces apoptosis of both ovarian follicles and human ovarian cancer cell lines.






Yadav V, Talwar P. Repositioning of fluoroquinolones from antibiotic to anti-cancer agents: An underestimated truth. Biomedicine & Pharmacotherapy. 2019;111:934-46.

Bucaneve G, Micozzi A, Menichetti F, Martino P, Dionisi MS, Martinelli G, et al. Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia. New England Journal of Medicine. 2005;353(10):977-87.

Carbon C. [Levofloxacin adverse effects, data from clinical trials and pharmacovigilance]. Therapie. 2001;56(1):35-40.

Tunitskaya VL, Khomutov AR, Kochetkov SN, Kotovskaya SK, Charushin VN. Inhibition of DNA Gyrase by Levofloxacin and Related Fluorine-Containing Heterocyclic Compounds. ActaNaturae. 2011;3(4):94-9.

He X, Yao Q, Hall DD, Song Z, Fan D, You Y, et al. Levofloxacin exerts broad-spectrum anticancer activity via regulation of THBS1, LAPTM5, SRD5A3, MFAP5 and P4HA1. Anti-cancer drugs. 2022;33(1):e235-e46.

Song M, Wu H, Wu S, Ge T, Wang G, Zhou Y, et al. Antibiotic drug levofloxacin inhibits proliferation and induces apoptosis of lung cancer cells through inducing mitochondrial dysfunction and oxidative damage. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2016;84:1137-43.

Kloskowski T, Szeliski K, Fekner Z, Rasmus M, Dąbrowski P, Wolska A, et al. Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment-The Effect of Dose-Response on 2D and 3D Cell Cultures. Int J Mol Sci. 2021;22(21).

McCormick M, Friehling E, Kalpatthi R, Siripong N, Smith K. Cost-effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia. Pediatric blood & cancer. 2020;67(10):e28469.

Urueta-Robledo J, Ariza H, Jardim JR, Caballero A, García-Calderón A, Amábile-Cuevas CF, et al. Moxifloxacin versus levofloxacin against acute exacerbations of chronic bronchitis: the Latin American Cohort. Respiratory medicine. 2006;100(9):1504-11.

Holtom PD, Pavkovic SA, Bravos PD, Patzakis MJ, Shepherd LE, Frenkel B. Inhibitory effects of the quinolone antibiotics trovafloxacin, ciprofloxacin, and levofloxacin on osteoblastic cells in vitro. Journal of Orthopaedic Research. 2000;18(5):721-7.

Erden B, Ulak G, Yildiz F, Utkan T, Ozdemirci S, Gacar N. Antidepressant, anxiogenic, and antinociceptive properties of levofloxacin in rats and mice. Pharmacology Biochemistry and Behavior. 2001;68(3):435-41.

Anderson VR, Perry CM. Levofloxacin : a review of its use as a high-dose, short-course treatment for bacterial infection. Drugs. 2008;68(4):535-65.

Johnson A. Intracellular mechanisms regulating cell survival in ovarian follicles. Animal reproduction science. 2003;78(3-4):185-201.

Ahmadifar M, Vahidi N, Fathi R. The Study of Effect of Levofloxacin on Disorders of Female Hormones in Rats. Anatomical Sciences Journal. 2014;11(2):71-4.

Norrby SR, Petermann W, Willcox PA, Vetter N, Salewski E. A comparative study of levofloxacin and ceftriaxone in the treatment of hospitalized patients with pneumonia. Scandinavian journal of infectious diseases. 1998;30(4):397-404.

Carbon C. Comparison of side effects of levofloxacin versus other fluoroquinolones. Chemotherapy. 2001;47(Suppl. 3):9-14.

Claudio T, Marcelo RP, Susana C, Ernesto G, Alberto N. Study of Sperm Apoptosis and Seminal Oxidant Capacity in Infertile Patients with Genital Tract Infections Evaluation of the Efficacy of Levofloxacin in Two Therapeutic Protocols. Advances in Sexual Medicine. 2012;2(2):21-4.

Serebryakova VA, Urazova OI, Novitsky VV, Vengerovskii AI, Kononova TE, Vasil'eva OA, et al. Effects of Levofloxacin on Blood Lymphocyte Apoptosis in Patients with Pulmonary Tuberculosis: an In Vitro Study. Bulletin of experimental biology and medicine. 2019;168(1):109-12.

Wang L, Wu Y, Tan Y, Fei, Xi, Deng Y, Cao H, et al. Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells. Journal of Applied Toxicology. 2014;34(8):870–7.

Ahmadi R, Ahmadifar M, Safarpour E, Vahidi-Eyrisofla N, Darab M, Eini AM, et al. The Effects of Levofloxacin on Testis Tissue and Spermatogenesis in Rat. Cell journal. 2016;18(1):112-6.

Sun J-p, Shi Z-y, Liu S-m, Kang Y-h, Hu G-q, Huangfu C-s, et al. Trimethoxy-benzaldehyde levofloxacin hydrazone inducing the growth arrest and apoptosis of human hepatocarcinoma cells. Cancer Cell International. 2013;13(1):1-10.

F. H, N. T, al. e. Benzaldehyde levofloxacin schiff base induces apoptosis of human hepatocarcinoma cells Chinese Pharmacological Bulletin. 2015;12:821-6.