From veterinary antibiotic to cancer therapy: revisiting anticancer potential of Monensin.

Monensin, a polyether ionophore widely used in veterinary medicine, has recently emerged as a multimodal anticancer candidate. This review provides a comprehensive overview of preclinical studies showing that monensin exerts selective cytotoxic and anti-progression effects across a wide range of malignancies. Its activity spans breast cancer to leukemia, reflecting both versatility and significant therapeutic potential. In breast cancer, monensin reduces proliferation, induces apoptosis, and enhances chemosensitivity, suggesting a role in combination therapies. In prostate cancer, it disrupts androgen receptor signaling, induces oxidative stress, and triggers mitochondria-dependent apoptosis. In pancreatic cancer, it suppresses EGFR signaling and promotes programmed cell death, while in ovarian and cervical cancers, it inhibits proliferation, migration, and invasion by modulating EGFR and MEK/ERK pathways and enhancing SUMOylation. In renal carcinoma, monensin induces cell-cycle arrest, autophagy, and apoptosis, whereas in bladder and squamous cell carcinoma, it interferes with EGFR-related signaling and lectin-mediated interactions. It selectively kills liver cancer cells through intracellular Na⁺ overload and mitochondrial damage, and in thyroid cancer, it disrupts cellular respiration and AMPK/mTOR signaling. In glioblastoma, it exhibits both anti-tumor and anti-angiogenic effects, while in hematologic malignancies such as leukemia and lymphoma, it induces apoptosis, cell-cycle arrest, and glycosylation alterations. Collectively, these findings highlight monensin as a highly promising, broad-spectrum anticancer candidate. Its multifaceted mechanisms of action and consistent efficacy across diverse tumor types provide a compelling rationale for continued preclinical evaluation and potential clinical translation. These insights position monensin as an innovative therapeutic avenue, offering new hope for the development of versatile and effective cancer treatments.