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印度辣木提取物派珀长胡椒可抑制管腔型乳腺癌细胞的细胞周期G1/S期转换并诱导内源性凋亡途径。

Piper chaba, an Indian spice plant extract, inhibits cell cycle G1/S phase transition and induces intrinsic apoptotic pathway in luminal breast cancer cells.

作者信息

Prajapati Kumari Sunita, Kumar Shashank

机构信息

Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Bathinda, Punjab, India.

出版信息

Cell Biochem Funct. 2023 Dec;41(8):1230-1241. doi: 10.1002/cbf.3857. Epub 2023 Sep 15.

DOI:10.1002/cbf.3857
PMID:37711079
Abstract

Piper chaba (Piperaceae) is a medicinal spice plant that possesses several pharmacological activities. In the present study, we for the first time studied the effect of P. chaba extract on breast cancer cells. P. chaba stem methanolic (PCSM) extract produced time and dose dependent cytotoxicity in luminal breast cancer cells (MCF-7 and T47D) with a minimal toxicity in breast normal cells (MCF-10A) at 10-100 µg/mL concentration. PCSM extract exerts 16.79 and 31.21 µg/mL IC for T47D and MCF-7 cells, respectively, in 48 h treatment. PCSM significantly arrests the T47D cells at the G0/G1 phase by reducing the CCND1 and CDK4 expression at mRNA and protein levels. PCSM extract treatment significantly altered nuclear morphology, mitochondria membrane potential, and production of reactive oxygen species in T47D cells at IC concentration. Extract treatment significantly altered the Bax/Bcl-2 ratio and altered caspase 8 and 3 mRNA/protein levels in T47D cells. Confocal microscopy showed an increase in late apoptosis in PCSM extract-treated breast cancer cells at IC . Further, an increased caspase 9 and caspase 3/7 enzymatic activity was observed in test cells compared with nontreated cells. In conclusion, P. chaba phytocompound possesses the potential to induce cell cycle arrest and induce apoptosis in luminal breast cancer cells.

摘要

荜拔(胡椒科)是一种具有多种药理活性的药用香料植物。在本研究中,我们首次研究了荜拔提取物对乳腺癌细胞的影响。荜拔茎甲醇提取物(PCSM)在管腔型乳腺癌细胞(MCF - 7和T47D)中产生了时间和剂量依赖性细胞毒性,在浓度为10 - 100μg/mL时对乳腺正常细胞(MCF - 10A)的毒性最小。在48小时处理中,PCSM提取物对T47D和MCF - 7细胞的IC50分别为16.79和31.21μg/mL。PCSM通过在mRNA和蛋白质水平上降低CCND1和CDK4的表达,显著将T47D细胞阻滞在G0/G1期。在IC50浓度下,PCSM提取物处理显著改变了T47D细胞的核形态、线粒体膜电位和活性氧的产生。提取物处理显著改变了T47D细胞中Bax/Bcl - 2的比例,并改变了caspase 8和3的mRNA/蛋白质水平。共聚焦显微镜显示,在IC50浓度下,PCSM提取物处理的乳腺癌细胞晚期凋亡增加。此外,与未处理的细胞相比,在测试细胞中观察到caspase 9和caspase 3/7酶活性增加。总之,荜拔植物化合物具有诱导管腔型乳腺癌细胞周期阻滞和诱导凋亡的潜力。

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