Insight into drug sensitizing effect of diallyl disulfide and diallyl trisulfide from Allium sativum L. on paclitaxel-resistant triple-negative breast cancer cells

Abstract

Ethnopharmacological relevanceAyurvedic practitioners and herbal healers in India and China have extensively used garlic (Allium sativum L.) to treat cancers. Diallyl disulfide (DADS) and diallyl trisulfide (DATS) are major volatile organosulfur phytochemical constituents found in garlic. Aim of the studyTo find new insight into the drug sensitizing effect of DADS and DATS on paclitaxel (PTX)-resistant triple-negative breast cancer cells (TNBC/PR). Materials and methodsThis study estimates the non-toxic concentration of DADS and DATS against normal healthy breast epithelial cell line (MCF-12A) by using a trypan blue viability assay. Also, it evaluates the effect of DADS and DATS on the sensitization of established stable TNBC/PR cell clones (MDA-MB 231 PR and MDA-MB 468 PR) by MTT, BrdU incorporation, intracellular ROS, cell cycle, and apoptosis assays. ResultsThe results show that DADS and DATS are non-cytotoxicity against MCF-12A cells. Nevertheless, DADS and DATS have shown significantly high cytotoxicity against MDA-MB 231 PR and MDA-MB 468 PR cells. They also inhibited PTX-resistant cell proliferation by blocking the cell cycle. Further, they induced apoptosis by activation of caspase 3 and 9. N-acetyl cysteine pre-treatment inhibited DADS and DATS-induced intracellular ROS release. In silico study shows that DADS and DATS interact with a large extracellular loop (LEL) of CD151 with a binding energy of −4.0 kcal/mol and transmembrane domain (TM) with a binding affinity of 11.7 and 13.6 kcal/mol, respectively. They also inhibited the surface expression of CD151 in TNBC/PR cells. ConclusionThis study implies that DADS and DATS could be considered for sensitizing drug-resistant breast cancers.