Anti-cancer activity of Biochanin A against multiple myeloma by targeting the CD38 and cancer stem-like cells. (December 2022)

• Record Type: Journal Article
• Authors: Jaina, Vinod Kumar; Eedara, Abhisheik; SVS, Sasi Priya; Jadav, Surender Singh; Chilaka, Sabarinadh; Sistla, Ramakrishna; Andugulapati, Sai Balaji
• Is Part Of: Process biochemistry. Volume 123(2022)
• Page Start: 11
• Page End: 26
• Publication Date: 2022-12
• Subjects: BCA Biochanin A -- MM Multiple Myeloma, BZM, Bortezomib -- Dexa dexamethasone -- SRB Sulforhodamine-B -- ROS Reactive Oxygen Species -- RT-qPCR Reverse transcriptase quantitative PCR -- h hour -- LND Lenalidomide -- MAPK mitogen-activated protein kinase -- NF-κB Nuclear factor kappa B -- μM micromolar -- PVDF polyvinylidene difluoride -- CSCs cancer stem cells -- FDA Food and Drug Administration; Multiple-myeloma -- Cancer stem cells -- Flavonoids -- CD38 -- Invasion -- NF-κB and MAPK; Biochemical engineering -- Periodicals; Biotechnology -- Periodicals; Biochemistry -- periodicals; Biotechnology -- periodicals; Chemical Engineering -- periodicals; Génie biochimique -- Périodiques; Biotechnologie -- Périodiques; Biochemical engineering; Biotechnology; Periodicals; 660.63
• DOI: 10.1016/j.procbio.2022.10.029
• Languages: English
• ISSNs: 1359-5113

Abstract

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. Graphical Abstract: ga1 Highlights: Biochanin A has a potential anti-cancer activity against multiple myeloma. Molecular docking confirms the binding of Biochanin A to CD38 receptor. Treatment with Biochanin A significantly mitigated the CD38 and CD44 levels. Biochanin A treatment ameliorated the in vitro and in vivo tumorgenicity, stemness and invasion. Biochanin A inhibits Nuclear factor kappa B and mitogen-activated protein kinase.