Despite advances in cancer therapy, conventional treatment modalities often remain insufficient in achieving optimal outcomes. To address these limitations, growing attention has been directed toward combining chemotherapeutic agents with natural compounds. The present study investigates the effects of co-treatment with mangiferin and paclitaxel on key cancer-related biological processes, including proliferation, apoptosis, autophagy, and angiogenesis. The cytotoxicity was assessed using the ATP assay on Ehrlich ascites carcinoma (EAC) and HUVECs. Protein expression in EAC cells was analyzed by western blotting. In vivo, tumor growth, cell death, and autophagic activity were examined in EAC tumors. Angiogenic responses were examined using In vitro tube formation and an In vivo chorioallantoic membrane assay. The combined treatment resulted in a synergistic cytotoxic effects. Increased LC3B and decreased p62, along with the induction of FAS and cleaved PARP, suggest involvement of both apoptosis and autophagy. In vitro results were consistent with in vivo. Mangiferin (50mg/kg) combined with paclitaxel showed the greatest tumor reduction with concurrent induction of apoptosis and autophagy. Furthermore, the co-treatment exhibited stronger anti-angiogenic effect than either compound alone.  In conclusion, mangiferin enhances the anticancer efficacy of paclitaxel by simultaneously targeting proliferation, programmed cell death, and angiogenesis. This supports the use of mangiferin as a promising natural agent for novel cancer treatment strategies.

To Cite This Article: Uvez A, Ulukaya E and Armutak EI, 2026. Mangiferin enhances the anticancer efficacy of paclitaxel by targeting apoptosis, autophagy, and angiogenesis. Pak Vet J, 46(3): 503-517. http://dx.doi.org/10.29261/pakvetj/2026.040