Betulinic Acid and Oleanolic Acid Modulate CD81 Expression and Induce Apoptosis in Triple-Negative Breast Cancer Cells through ROS Generation

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by a lack of hormones and the HER2 receptor, making it unresponsive to targeted therapy. Triterpenoids such as betulinic acid (BA) and oleanolic acid (OA) have anticancer effects by inducing apoptosis in TNBC cells. CD81 is a tetraspanin that affects the growth and metastasis of cancer cells. Aim To evaluate the effect of BA and OA on viability MDA-MB 231 by analyzed of CD81 expression, intracellular ROS and apoptosis. Materials and Methods The TNBC cell, MDA-MB 231, was cultured and exposed by BA dan OA. The viability cell was evaluated by the CCK-8 assay. The binding of BA dan OA to CD81 was analyzed using molecular docking. This study evaluated CD81 expression, intracellular ROS, and apoptosis by flow cytometri. Results The result showed that BA and OA inhibited viability of MDA-MB-231 cells. BA and OA bind to CD81 in silico, with binding affinities of 9.0 kcal/mol for BA and 7.2 kcal/mol for OA. Flow cytometry results revealed that BA can downregulate CD81 expression. BA and OA also increased intracellular ROS levels and induced apoptosis. Conclusion These findings suggest that BA and OA, especially BA, can modulate CD81 expression and promote apoptosis in TNBC cells through the generation of ROS, thereby offering a potential therapeutic strategy for the treatment of TNBC.