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Myricetin-induced apoptosis in triple-negative breast cancer cells through inhibition of the PI3K/Akt/mTOR pathway

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Abstract

Breast cancer is still a severe origin of malignant demise in females, and its prevalence is rising worldwide. Triple-negative breast cancer (TNBC) is a diversified aggressive breast tumor distinguished by inadequate prognosis, early recurrence, high invasion, and extremely metastasized disease. Chemotherapy is being used to treat it; however, it has low efficacy. On the other hand, with the growing number of corroborations on subtypes of TNBC and molecular biology of tumors, significant advancement in TNBC targeted treatment has been made. Myricetin (MYR), a polyhydroxyflavonol compound widely found in nature, has been shown to possess anticancer effects in various cancers. Though, the mechanisms and impacts of MYR on metastasis of TNBC remain unclear. Early and late apoptotic cell death and cell proliferation inhibition were observed in MYR-treated TNBC cells. MYR modulated cell cycle, pro-angiogenic, and invasion effects via the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Protein kinase B (PKB/also known as AKT) signaling pathways. Moreover, it regulates the expression of MAPK, PI3K/AKT/mTOR, IκB/NF-κB, Hippo, STAT3, GSK-3β, Nrf2/HO-1, TLR, eNOS / NO, ACE, and AChE. Here, we review the anticancer effects of MYR for TNBC and target the PI3K/AKT/mTOR pathway as a therapeutic target for the fruitful treatment of TNBC to summarize MYR's therapeutic potential.

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Acknowledgements

Authors are thankful to ICMR

Funding

This work was supported by the Indian Council of Medical Research, Grant Number [45/24/2020-Nan-BMS].

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University), Delhi, 110062, India

    Preeti Sharma, Mohammad Ahmed Khan, Abul Kalam Najmi & Mohd Akhtar

  2. Division of Cyclotron and Radiopharmaceutical Sciences, INMAS, DRDO, Timarpur, Delhi, 110054, India

    Shubhra Chaturvedi

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PS—Conceptualization, methodology, Investigation, Data Curation, Software, validation, Writing, Original Draft, and Writing—Review and editing & Formal analysis. MAK—Resources and Supervision. AKN—Resources and Supervision. SC—Resources and Supervision. MA—Resources & Supervision.

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Sharma, P., Khan, M.A., Najmi, A.K. et al. Myricetin-induced apoptosis in triple-negative breast cancer cells through inhibition of the PI3K/Akt/mTOR pathway. Med Oncol 39, 248 (2022). https://doi.org/10.1007/s12032-022-01856-z

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