The multifaceted effects of rosmarinic acid on breast cancer, regulating autophagy and increasing apoptosis

Cancer remains a complex and formidable disease that necessitates the development of diverse therapeutic strategies, including the investigation of natural products as complementary agents. Rosmarinic acid (RA), a phenolic compound, has demonstrated promising anticancer activity across various malignancies. Combining RA with conventional chemotherapeutic agents may represent a novel therapeutic approach. In the present study, the efficacy of these combinations was evaluated <i>in vitro</i> through the assessment of cell viability, apoptosis, autophagy, and proliferation, and <i>in vivo</i> by examining their effects on tumor growth in an Ehrlich Ascites Carcinoma (EAC) model. Among the tested combinations, RA and Paclitaxel (PTX) exhibited enhanced cytotoxicity and synergistic activity compared with individual treatments, whereas other combinations demonstrated limited efficacy. Morphological and moleculer analyses indicated induction of apoptosis, evidenced by increased expression of FAS, FADD, and cleaved caspases detected by Western blotting. Moreover, the RA+PTX (Rosmarinic acid + Paclitaxel) combination was associated with impaired autophagic flux, as reflected by elevated LC3 and p62 levels. Although the combined treatment reduced tumor volume <i>in vivo</i>, its antitumor efficacy was comparable to that of RA monotherapy. Collectively, these findings indicate that while the RA+PTX combination enhanced cytotoxicity activity against triple-negative breast cancer <i>in vitro</i>, its therapeutic advantage <i>in vivo</i> requires further investigation.