Peimine Inhibits MCF-7 Breast Cancer Cell Growth by Modulating Inflammasome Activation: Critical Roles of MAPK and NF-kappa B Signaling

作者全名："Sun, Jingqiu; Li, Jing; Kong, Xin; Guo, Qingfeng"

作者地址："[Sun, Jingqiu; Guo, Qingfeng] Jiangnan Univ, Dept Thyroid & Hernia Surg, Affiliated Hosp, Wuxi, Jiangsu, Peoples R China; [Li, Jing] Shenzhen Tradit Chinese Med Hosp, Dept Liver Dis, Shenzhen, Peoples R China; [Kong, Xin] Chongqing Med Univ, Clin Lab, Tried Affiliated Hosp, Gener Hosp, Chongqing, Peoples R China"

通信作者："Sun, JQ (通讯作者)，Jiangnan Univ, Dept Thyroid & Hernia Surg, Affiliated Hosp, Wuxi, Jiangsu, Peoples R China."

来源：ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001023381800007

JCR分区：Q3

影响因子：2.6

年份：2023

卷号：23

期号：3

开始页：317

结束页：327

文献类型：Article

关键词：Peimine; breast cancer; inflammasomes; NF-kappa B; MAPK; MCF-7

摘要："Objective: Peimine (PM) is a bioactive compound obtained from Fritillaria. It has been documented that PM exhibits potent antitumor properties against multiple cancers. However, the antitumor properties of PM in breast cancer and its associated mechanisms have not been clarified. Methods: Proliferation and apoptosis of MCF-7 and MCF-10A cells were detected by CCK8, colony formation, and flow cytometry assays. Cytotoxicity was measured by Lactate dehydrogenase (LDH) leakage assay. The level of IL-1 beta and IL-18 were detected with ELISA kits. Western blotting and real-time Polymerase Chain Reaction were performed to analyze the expression of proteins and genes related to the NLRP3 inflammasome pathway and Endoplasmic reticulum stress. Results: The doses of PM (5, 10, and 20 mu M) inhibited cell viability significantly, apoptotic induction, and inflammasome activation in breast cancer cells in vitro. Inflammasome components were decreased, including the apoptosis-associated speck like protein containing a CARD (ASC) and NOD-like receptor pyrindomain-containing protein3 (NLRP3), as well as the inhibition of caspase-1 and interleukin-1 beta activation. Moreover, inflammasome inhibitors suppressed cell growth and induced apoptosis, implying that PM suppresses the growth of breast cancer cells through regulating inflammasome. Mechanistically, PM inhibited the activity of inflammasome by alleviating endoplasmic reticulum (ER) stress and by down-regulating the expression of multiple proteins in transcription factor nuclear factor-kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPKs) signaling pathways. Conclusion: These findings show that PM suppresses the growth of breast cancer cells by inhibiting inflammasome activation, to a certain extent, by primarily acting on the MAPK/NF-kappa B pathway's inactivation-dependent mechanisms."

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