Exploring potential molecular targets and therapeutic efficacy of beauvericin in triple-negative breast cancer cells.

Triple negative breast cancer (TNBC) presents a significant global health concern due to its aggressive nature, high mortality rate and limited treatment options, highlighting the urgent need for targeted therapies. Beauvericin, a bioactive fungal secondary metabolite, possess significant anticancer potential, although its molecular targets in cancer cells remain unexplored. This study has investigated possible molecular targets of beauvericin and its therapeutic insights in TNBC cells. In silico studies using molecular docking and MD simulation predicted the molecular targets of beauvericin. The identified targets included MRP-1 (ABCC1), HDAC-1, HDAC-2, LCK and SYK with average binding energy of -90.1, -44.3, -72.1, -105 and -60.8 KJ/mol, respectively, implying its multifaceted roles in reversing drug resistance, inhibiting epigenetic modulators and oncogenic tyrosine kinases. Beauvericin has significantly reduced the viability of MDA-MB-231 and MDA-MB-468 cells, with IC ₅₀ concentrations of 4.4 and 3.9 µM, while concurrently elevating the intracellular ROS by 9.0 and 7.9 folds, respectively. Subsequent reduction of mitochondrial transmembrane potential in TNBC cells, has confirmed the induction of oxidative stress, leading to apoptotic cell death, as observed by flow cytometric analyses. Beauvericin has also arrested cell cycle at G1-phase and impaired the spheroid formation and clonal expansion abilities of TNBC cells. The viability of spheroids was reduced upon beauvericin treatment, exhibiting IC ₅₀ concentrations of 10.3 and 6.2 µM in MDA-MB-468 and MDA-MB-231 cells, respectively. In conclusion, beauvericin has demonstrated promising therapeutic potential against TNBC cells through possible inhibition of MRP-1 (ABCC1), HDAC-1, HDAC-2, LCK and SYK.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Siddhartha Sankar Ghosh reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology. Siddhartha Sankar Ghosh reports financial support was provided by Indian Council of Medical Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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