Anti-cancer activity of Biochanin A against multiple myeloma by targeting the CD38 and cancer stem-like cells

Abstract

Multiple myeloma (MM) is a malignant neoplasm of B-cells characterised by the uncontrolled proliferation of plasma cells in the bone marrow. Despite the advancements in MM treatment, it has a poor prognosis with a median survival of 3–5 years. CD38 has been one of the key therapeutic targets for MM, due to its high expression in MM cells conferring its role in immune evasion and cancer progression. Therefore, novel compounds targeting CD38 with low toxicity are warranted for improved MM therapy. In this study we aimed to investigate the anticancer activity of Biochanin A (BCA), an isoflavone, against Multiple myeloma. BCA treatment induced apoptosis in MM cells and showed reduced cytokine expression levels. In-addition, BCA significantly reduced the CD38 population and cancer stem-cell markers in dose dependent manner. Consistently, we observed BCA treatment significantly reduced the stemness markers and invasion capability of cells. Furthermore, BCA treatment significantly attenuated the tumour growth in U266 induced tumour model in NOD/SCID mice. Mechanistic studies revealed that BCA anti-cancer activities are exerted by modulating the NF-κB and MAPK signalling pathways. Overall, this study enlightens the application of BCA as a novel treatment modality for multiple myeloma with superior efficacy and reduced toxicity.