ABSTRACT:
Drug repositioning has emerged as a strategic approach in pharmaceutical research, addressing challenges related to productivity, regulatory hurdles, and escalating development costs. Fluoroquinolones, a class of broad-spectrum antibiotics, have demonstrated notable anticancer properties, primarily through inhibition of topoisomerase II, a mechanism shared with several established anticancer agents. This study aimed to evaluate the anticancer potential of different generations of fluoroquinolones, including ciprofloxacin, moxifloxacin, and levofloxacin, in an in vivo model of carcinogen-induced breast tumors. Female Balb/c mice were chronically administered a combination of 7,12-dimethylbenz[a]anthracene (DMBA) and medroxyprogesterone acetate (MPA) to induce mammary tumors. Tumor-bearing mice were randomized into treatment groups and received daily oral doses of the selected fluoroquinolones or vehicle for 14 days. Tamoxifen was included as a reference standard. Tumor progression, serum estradiol levels, body weight, hematological, and serum biochemical parameters were assessed to evaluate therapeutic efficacy. All fluoroquinolone-treated groups exhibited reduced tumor progression and lower serum estradiol levels than the diseased-control group. Improvements in body weight, hematological, biochemical, and serum estradiol profiles of mice indicated a protective effect of fluoroquinolone treatment. Among the tested agents, moxifloxacin demonstrated superior antitumor activity, evidenced by a greater reduction in tumor incidence and weight relative to ciprofloxacin and levofloxacin. The comparative analysis suggests that moxifloxacin possesses enhanced antitumor efficacy in a murine model of mammary tumors induced by carcinogens, outperforming ciprofloxacin and levofloxacin. These findings support further investigation of moxifloxacin as a potential anticancer drug for repositioning in combination with standard-of-care treatment.