6C potency of Terminalia chebula reveals secondary metabolites and induces apoptosis in Triple-Negative Breast Cancer Cells (TNBCs)

Abstract

Background: Breast cancer is a prevalent malignancy in women globally, and TNBCs, being ER-/PR-/Her2-, pose challenges in treatment options. Complementary and alternative medicines, including homoeopathic remedies, have gained popularity as potential anti-cancer agents to mitigate the side effects of conventional drugs. Previously, the anticancer activity of homoeopathic potencies of Terminalia chebula (MT, 3X, 6C, and 30C) against breast cancer cell lines has been reported. Objectives: This study aimed to evaluate the mechanism of anticancer activity of 6C potency of T. chebula against the TNBC cell line, MDAMB231 and to understand the phytochemical composition of 6C potency. Methods: Lactate release was studied by LDH assay, and mitochondrial membrane potential was evaluated by JC-1 assay. The mRNA expression of tumour suppressor and pro-apoptotic genes was done by qRT-PCR assay. Mother Tincture (MT) and 6C potencies were phytochemically characterised by LCMS analysis. Results: The 6C potency of TC increased lactate release in TNBCs, indicating a shift towards glycolysis and potentially inducing metabolic changes that contribute to its anticancer activity. The increased lactate release led to loss of mitochondrial membrane potential and an increase in mRNA expression of pro-apoptotic markers (caspase 3, caspase 9, and cytochrome c) and tumour suppressor proteins (p53 and pRb). LCMS analysis of 6C potency revealed phytocompounds with anticancer, anti-inflammatory, and antioxidant activities. Conclusion: The 6C potency of T. chebula induced apoptosis in TNBCs, however, further in vivo effi cacy and safety studies are warranted to understand the anti-cancer mechanism of 6C in-depth.