Betulinic acid is associated with miR-21 modulation, apoptosis and redox changes in breast cancer cells: an in vitro and in silico study

Betulinic acid is defined as a hydrophobic pentacyclic triterpenoid primarily found in the bark of Betula alba, known for its anticancer activity through mechanisms such as upregulating proapoptotic proteins, modulating NF-kB, and inhibiting topoisomerase I. The current study aimed to explore the anticancer potential effect, molecular targets, and association with miR-21 modulation after BA treatment and its combination with doxorubicin against human triple-negative breast cancer (MDA-MB-231) cells. We determined drug cytotoxicity by MTT assay, and death mechanism by flow cytometry. Besides, the potential effect of BA and DOX treatment on downstream effect of miR-21 on HIF1A, PDCD4, PTEN and SMAD7 expression levels. Finally, a molecular docking study was performed to determine molecular targets, binding affinity, and mode of interactions of BA and DOX with HIF1A, PDCD4, PTEN and SMAD7. Collectively, our data showed that treatment with BA and/or DOX have significantly describing observed differences under the tested conditions associated with increasing apoptosis, downregulation of miR-21, HIF1A and SMAD7 expression and upregulation of PDCD4 and PTEN. Finally, the molecular docking study suggested potential interactions between BA and DOX with PTEN and PDCD4, modulating their activities leading to growth arrest and cell death. In conclusion, this study reported BA as potential antiproliferative compound with modulation of miR-21 expression and identified molecular targets involved in its action.