Therapeutic Trial of Modified Levofloxacin (MOLVX) Against Induced Colorectal Aberrant Crypt Foci (Precancerous Tissue) in Mice

Abstract

Colorectal cancer ranks as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths globally. ‎Fluoroquinolones, particularly Levofloxacin, have garnered interest for their potential anti-cancer effects, primarily due to their high affinity ‎for metallic ions like copper. This affinity enhances their spectrum of activity and enables greater interaction with DNA in cancer cells, ‎thereby inhibiting proliferation. Building on our prior work, where we synthesized copper-modified Levofloxacin (MOLVX), this study ‎explores its therapeutic potential in treating precancerous colorectal lesions, known as Aberrant Crypt Foci (ACF), in a murine model. Sixty ‎female Balb-C mice were randomized into six groups (n=10 per group). The first group served as a negative control and received no treatment. ‎The remaining groups were administered azoxymethane (AOM) at 10 mg/kg body weight (BW) twice weekly to induce ACF. Among these, the ‎second group acted as a positive control and received no further treatment. The third group was intraperitoneally administered doxorubicin at ‎‎16.2 mg/kg BW once a week for four weeks. The fourth group was treated with Levofloxacin at 25 mg/kg BW via oral lavage daily for four ‎weeks. The final two groups received daily oral lavage treatments of MOLVX at doses of 5 mg/kg and 2.5 mg/kg BW for four weeks, ‎respectively. Histopathological analysis of ACF tissues, stained with hematoxylin and eosin, revealed a statistically significant reduction ‎‎(P<0.05) in ACF count among groups treated with MOLVX, doxorubicin, and Levofloxacin, compared to the positive control. Additionally, both ‎MOLVX-treated groups showed a significant decrease (P<0.05) in proliferating cellular antigen (PCNA) levels. In conclusion, both MOLVX ‎dosages (2.5 mg/kg and 5 mg/kg BW) demonstrated promising therapeutic efficacy against precancerous colorectal lesions in mice. However, ‎the 5 mg/kg BW dose appeared to be more potent.