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<p>Phytochemical analysis of the aerial parts of <i>Centaurea schmidii</i> Wagenitz (Asteraceae) led to the isolation of disafynol, a novel polyacetylene, for the first time. This study investigated its anti-cancer effects and the mechanisms underlying these effects in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive) breast cancer cell lines. The cytotoxic effects of disafynol were evaluated using various concentrations to measure cell viability, apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), caspases-12/6 activity, and protein aggregation. Expression of apoptotic markers and endoplasmic reticulum (ER) stress-related genes was analyzed by western blot and reverse transcription‐PCR analyses, respectively. Disafynol exhibited dose-dependent cytotoxicity, with greater potency in MDA-MB-231 cells (IC50: 10.6&#xa0;µM) compared to MCF-7 cells (IC50: 30&#xa0;µM), indicating hormone receptor-independent manner of cell growth inhibition. Treating cells with disafynol caused significant apoptosis, marked by enhanced ROS production and reduced MMP. Meanwhile, disafynol induced Bcl-2 downregulation, Bax upregulation, and caspase-12/6 activities in both breast cancer cells. Additionally, disafynol triggered ER stress, as evidenced by protein aggregation and upregulation of genes related to ER stress, including BIP, ATF4, CHOP, and XBP-1. Overall, disafynol demonstrates significant pro-apoptotic effects on breast cancer cells by inducing oxidative stress and activating the ER stress pathway. Its hormone receptor-independent cytotoxicity suggests potential therapeutic applications for treating breast cancers, including triple-negative subtypes.</p> Graphical Abstract <p></p>

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Disafynol: A polyacetylene dimer from Centaurea schmidii enhancing breast cancer cell apoptosis via oxidative and ER stress pathways

  • 期刊论文

  • 发表日期：

    2025年3月28日

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  • Zeinab Babaei,
  • Mustafa Ghanadian,
  • Mahmoud Aghaei

摘要

Phytochemical analysis of the aerial parts of Centaurea schmidii Wagenitz (Asteraceae) led to the isolation of disafynol, a novel polyacetylene, for the first time. This study investigated its anti-cancer effects and the mechanisms underlying these effects in MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor-positive) breast cancer cell lines. The cytotoxic effects of disafynol were evaluated using various concentrations to measure cell viability, apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), caspases-12/6 activity, and protein aggregation. Expression of apoptotic markers and endoplasmic reticulum (ER) stress-related genes was analyzed by western blot and reverse transcription‐PCR analyses, respectively. Disafynol exhibited dose-dependent cytotoxicity, with greater potency in MDA-MB-231 cells (IC50: 10.6 µM) compared to MCF-7 cells (IC50: 30 µM), indicating hormone receptor-independent manner of cell growth inhibition. Treating cells with disafynol caused significant apoptosis, marked by enhanced ROS production and reduced MMP. Meanwhile, disafynol induced Bcl-2 downregulation, Bax upregulation, and caspase-12/6 activities in both breast cancer cells. Additionally, disafynol triggered ER stress, as evidenced by protein aggregation and upregulation of genes related to ER stress, including BIP, ATF4, CHOP, and XBP-1. Overall, disafynol demonstrates significant pro-apoptotic effects on breast cancer cells by inducing oxidative stress and activating the ER stress pathway. Its hormone receptor-independent cytotoxicity suggests potential therapeutic applications for treating breast cancers, including triple-negative subtypes.

Graphical Abstract