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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1434812

Blestriarene C Exerts An Inhibitory Effect on Triple-Negative Breast Cancer through Multiple Signaling Pathways

Provisionally accepted
Junsha An Junsha An 1,2Mingyu Han Mingyu Han 1Hailin Tang Hailin Tang 3Cheng Peng Cheng Peng 2*Wei Huang Wei Huang 2*Fu Peng Fu Peng 1*
  • 1 Sichuan University, Chengdu, China
  • 2 Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
  • 3 Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, Guangdong Province, China

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

    Breast cancer is the most common cancer worldwide, the leading cause of cancer death in women, and the fifth leading cause of cancer death. Triple negative breast cancer (TNBC), with high metastasis and mortality rates, is the most challenging subtype in breast cancer treatment. There is an urgent need to develop anti-TNBC drugs with significant efficacy, low side effects and good availability. In early drug screening, blestriarene C was found to have inhibitory effects on TNBC cells. Network pharmacology analysis was used to predict the active components in Baiji, and to investigate the hub targets and related mechanisms of BC in TNBC treatment. The mechanism of anti-TNBC in vitro was evaluated by CCK-8 assay, cell apoptosis and cell cycle assays, wound healing assay, WB assay, and molecular docking analysis. The inhibition effect in vivo was test in subcutaneous tumor models established in mice. Through network pharmacology analysis and experiments, we screened out BC as the main active ingredient, and found that BC could inhibit the Ras/ERK/c-Fos signaling pathway while downregulating the expression of HSP90AA1 and upregulating the expression of PTGS2, thereby promoting apoptosis, causing S-phase cycle arrest, and inhibiting the proliferation and migration of BT549 cells. The in vivo results illustrated that BC inhibited the growth of TNBC tumors and has a high safety profile. By integrating network pharmacology with in vitro and in vivo experiments, this study demonstrated that BC inhibited the proliferation and migration of TNBC cells by inhibiting the Ras/ERK/c-Fos signaling pathway, promoting apoptosis, and causing S-phase cycle arrest. This study provides new evidence for the use of BC as a novel drug for TNBC treatment.

    Keywords: Blestriarene C, Triple-negative breast cancer, Network Pharmacology, HSP90AA1, PTGS2

    Received: 18 May 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 An, Han, Tang, Peng, Huang and Peng. 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:
    Cheng Peng, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, China
    Wei Huang, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, China
    Fu Peng, Sichuan University, Chengdu, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.