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Proteomics-based network pharmacology and molecular docking reveal the potential mechanisms of 5,6,7,4′-tetramethoxyflavone against HeLa cancer cells

Year: 2024

Type: article

Abstract: Context5,6,7,4'-tetramethoxyflavone (TMF) is a citrus dietary polymethoxyflavone (PMF). Our previous study revealed that TMF has inhibitory effect on HeLa cancer cells. However, the mechanisms underlying the effects of TMF remain unclear.ObjectiveTo explore the underlying mechanisms of action of TMF against HeLa cancer cells for the first time.Materials and methodsHeLa cells were treated with 50 μmol/L TMF or dimethyl sulfoxide (DMSO) for 24 h. The protein expression levels of HeLa cells after TMF exposure were determined using antibody arrays, and the differentially expressed proteins (DEPs) were analyzed using network pharmacology and molecular docking.ResultsTMF treatment resulted in 37 DEPs, including 31 upregulations (CD40, CD40L, Fas, Fas-L, HSP27, HSP60, IGFBP-1, IGFBP-2, IGF-1sR, Livin, p21, p27, sTNFR2, TRAILR2, TRAILAR3, TRAILR4, XIAP, p-Sre, p-Stat1, p-Stat2 p-c-Fos, p-Smad1, p-Smad2, p-Smad4, p-Smad5, p-IkBa, p-MSK1, p-NFκB, p-TAK1, p-TBK1, p-ZAP70 and p-MSK2), and 6 downregulations (p-EGFR, p-ATF2, p-cJUN, p-HSP27, p-JNK, and p-GSK3A). Network pharmacology analysis revealed that the inhibitory effect of TMF on HeLa cancer was primarily involved in MAPK signaling pathway, apoptosis signaling pathway, and TNF signaling pathway. In addition, molecular docking analysis suggested that JUN, p53, NFKBIA, CDKN1B, and XIAP were core targets responsible for TMF efficacy against HeLa cancer.Discussion and conclusionThis study explored and illuminated the possible signaling pathways and potential targets of TMF on HeLa cancer cells, providing feasible ideas and facilitation for further studies on the mechanisms and medical potential of TMF.

Source: Heliyon

DOI: 10.1016/j.heliyon.2024.e38951

Authors: Qiang You, Lan Li, Haiyan Ding, Youping Liu

Institutions: Chengdu University of Traditional Chinese Medicine, Hainan Medical University, Peking University

Language: English

Topic: Bioactive Compounds in Plants

Subfield: Plant Science

Field: Agricultural and Biological Sciences

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,100