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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1531220
This article is part of the Research Topic Decoding the Epigenetic Landscape: Elucidating Cancer Pathology and Identifying Novel Therapeutic Targets View all 12 articles

Contribution of NCAPD3-dependent ferroptosis of 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-glucoside inhibiting the proliferation in T47D cells

Provisionally accepted
Jianfen Shen Jianfen Shen 1Shuo Zhang Shuo Zhang 2*Yan Song Yan Song 2*Leiming Yang Leiming Yang 2*Qi Huang Qi Huang 2*Pengyu Wang Pengyu Wang 2*Youzhi Zhang Youzhi Zhang 2*
  • 1 Department of Central Laboratory, The Affiliated Hospital of Jiaxing University, Jiaxing, China
  • 2 School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China

The final, formatted version of the article will be published soon.

    Objective: Non-SMC condensin II complex subunit D3 (NCAPD3) has recently been demonstrated as a crucial oncogenic factor, nevertheless, the biological role of NCAPD3 in the pathogenesis of breast cancer has not been elucidated. Evidence suggests that targeting ferroptosis can inhibit the progression of breast cancer. Moreover, THSG could modulate MCF-7 cell proliferation in our previous study. Therefore, we aimed to investigate the potential mechanism by which NCAPD3 mediates ferroptosis in THSG inhibition of T47D cell proliferation by full-length transcriptome sequencing.Methods: Alternative splicing analysis was performed based on full-length transcriptome sequencing and the overlapping genes in DETs and diAS were obtained. Further, RT-PCR was used to validate the type of alternative splicing. And the hub genes (transcripts) were selected using the bioinformatics analysis, quantitative polymerase chain reaction (qPCR) and western blotting (WB). Moreover, cell cycle and ferroptosis were assessed using flow cytometry analysis and WB respectively. Mechanically, cell viability and clone formation was detected using Biochemical kit. And siRNA of Ncapd3 was transfected into T47D cells to detect the expression levels of ferroptosis-related proteins (WB) and cell viability (MTT).Results: 40 overlapping transcripts of DETs and diAS were obtained consistent with the analysis of full-length transcriptome sequencing, and Ncapd3 (Ncapd3-203) is key gene (transcript), which was also highly expressed in breast cancer and THSG could inhibit the mRNA and protein expression. Moreover, THSG could induce cell cycle arrest in G2/M stage and reduce ferroptosis-related protein expression (xCT and GPx4). Mechanically, we found that THSG inhibits the cell proliferation and clone formation in T47D cells, and Ncapd3 inhibition could inhibit (xCT and GPx4) proteins expression, which regulated THSG-suppressing effect in T47D cells.THSG could inhibit the proliferation in T47D cells by NCAPD3 -dependent ferroptosis, which provided novel insights into targeted strategy for breast cancer.

    Keywords: THSG, NCAPD3, breast cancer, ferroptosis, full-length transcriptome sequencing, T47D cells

    Received: 20 Nov 2024; Accepted: 31 Dec 2024.

    Copyright: © 2024 Shen, Zhang, Song, Yang, Huang, Wang and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Shuo Zhang, School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China
    Yan Song, School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China
    Leiming Yang, School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China
    Qi Huang, School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China
    Pengyu Wang, School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China
    Youzhi Zhang, School of Pharmacy, Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning Medical College, Hubei University of Science and Technology, xianning, China

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