Broad-Spectrum Antibiotics Attenuate the Chemotherapeutic Efficacy of Doxorubicin in MDA-MB-468 Breast Cancer Cells

Abstract

Background: Breast cancer remains a global health challenge due to rising incidence, chemoresistance, and tumor relapse. In cancer management, antibiotics are often used to treat bacterial infections in immunocompromised patients. However, the direct impact of antibiotics on cancer progression and treatment outcomes is not well understood. This study investigated the effects of four antibiotics—ciprofloxacin, amoxicillin-clavulanic acid, tetracycline, and meropenem—on breast cancer cells, both alone and in combination with the chemotherapeutic agent doxorubicin (DOX). Methods: Using the MDA-MB-468 breast cancer cell line, we assessed cell viability using the MTT assay. The impact of antibiot ics on apoptosis was assessed using Annexin V/PI flow cytometry. Additionally, we evaluated the expression of stem cell markers CD133, CD44, and CD24 posttreatment using flow cytometry. Finally, the Luminex assay was used to measure the cytokine and chemokine release by the cells. Results: All of the antibiotics reduced cell viability in a time- and dose-dependent manner but reduced DOX-induced cytotox icity. The antibiotics also induced early apoptosis in the cells but significantly reduced DOX-induced apoptosis, supporting our earlier observation that these antibiotics diminish the efficacy of DOX chemotherapy. Furthermore, amoxicillin-clavulanic acid, ciprofloxacin, and meropenem diminished the efficacy of DOX chemotherapy by promoting stemness in cancer cells. The antibi otics exhibited variable effects on cytokine and chemokine production. Conclusion: Although these antibiotics exhibit anticancer activity, their coadministration with DOX may reduce its therapeutic efficacy and promote cancer stemness. These findings highlight the need for further investigation into antibiotic–chemotherapy interactions in breast cancer treatment.