Journal
JOURNAL OF MOLECULAR STRUCTURE
Volume 1258, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.molstruc.2022.132668
Keywords
Breast cancer; IL-6/STAT3 signaling pathway; Molecular docking; Molecular dynamics simulation; Cytotoxicity assay
Categories
Funding
- Institute of Eminence, University of Delhi [IoE/FRP/LS2020/27]
- Indian Council of Medical Research (ICMR) , New Delhi
- All India Institute of Medical Sciences, New Delhi
- DBT
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Phytotherapy for breast cancer, as an adjuvant therapy, has shown potential in overcoming the challenges of chemotherapy and radiotherapy. In this study, the researchers identified genistein as a phytocompound with excellent binding energy to the IL-6/IL-6R alpha interface of the STAT3 pathway. They propose genistein as a potential therapeutic compound to inhibit the IL-6/STAT3 pathway in breast cancer.
Phytotherapy for breast cancer, the second most common cancer diagnosed among women and a leading cause of their death globally, may serve as an adjuvant therapy to combat adverse chemo-and radiotherapy challenges. IL-6/STAT3 signaling pathway, governing breast cancer progression, remains a favourite therapeutic target in developing phytotherapy. Therefore, identifying phytocompounds with novel targets influencing the IL-6/STAT3 pathway would help to develop phytotherapy for breast cancer. In this study, we demonstrate the novel binding site, i.e., the interface of IL-6 and IL-6R alpha of the IL-6/STAT3 signaling pathway of cancer progression. Ten potent anticancer phytocompounds were analyzed for their binding with IL-6/IL-6R alpha complex using molecular docking and molecular dynamics simulations. Among all, genistein showed excellent binding energy (-10.59 kcal/mol) with the IL-6/IL-6R alpha interface of the STAT3 pathway. In cytotoxicity experiment, Genistein showed IC50 of 38 mu M and 18 mu M for 24 and 48 h, respectively, whereas quercetin showed IC50 of more than 50 mu M and 35 mu M at 24 h and 48 h, respectively on MDA-MB-453 breast cancer cell line. Based on bioinformatic analyses and cellular toxicity assay, we propose genistein as a potential therapeutic phytocompound to inhibit the IL-6/STAT3 pathway by blocking the interaction of IL-6 with the IL-6 receptor.(c) 2022 Elsevier B.V. All rights reserved.
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