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来自波斯湾的 对乳腺癌细胞的线粒体促凋亡特性及其化学成分。

Mitochondrial Pro-Apoptotic Properties of from Persian Gulf against Breast Cancer Cells and Its Chemical Composition.

机构信息

Department of Pharmacognosy, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R, Iran.

Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R, Iran.

出版信息

Nutr Cancer. 2022;74(6):2276-2290. doi: 10.1080/01635581.2021.2007961. Epub 2021 Nov 26.

Abstract

Locals in the Persian Gulf islands traditionally use to treat cancer. Therefore, this study deals with the cytotoxic activity of the soft coral chloroform extract (SCE), its pro-apoptotic activity, and the determination of its secondary metabolites. Cytotoxicity was done against MCF-7 and MDA-MB-231 and MCF‑10A cells. Apoptosis induction was checked by flow cytometry. The DCFDA and JC-1 probes were used to assess the production of reactive oxygen species (ROS) and the mitochondrial transmembrane potential. Caspase-9, Bax, and Bcl-2 proteins were determined with ELISA Kit, and by western blot analysis. SCE exhibited cytotoxic activity with an IC value of 32.51 ± 0.70 μg/ml against MCF-7, and 8.53 ± 0.97 μg/ml against MDA-MB-231 cancer cells. The induction of the intrinsic apoptosis pathway was found by ROS generation, attenuation of Bcl-2 and induction of Bax proteins. It was supported by activation of caspase-9, increased apoptotic cells, as well as decrease of ΔΨm. In the acute toxicity, there was no detectable sign of hepatic or renal toxicity in the SCE 100 mg/kg. GC mass and NMR identified bioactive compounds as one monoterpene, one sesquiterpene, five fatty acids, one phthalate, and two steroidal compounds.

摘要

传统上,波斯湾岛屿的当地人使用 来治疗癌症。因此,本研究涉及软珊瑚氯仿提取物 (SCE) 的细胞毒性活性、促凋亡活性及其次生代谢物的测定。使用 MCF-7 和 MDA-MB-231 以及 MCF-10A 细胞进行细胞毒性测定。通过流式细胞术检查细胞凋亡诱导。使用 DCFDA 和 JC-1 探针评估活性氧 (ROS) 的产生和线粒体跨膜电位。使用 ELISA 试剂盒和 Western blot 分析测定 caspase-9、Bax 和 Bcl-2 蛋白。SCE 对 MCF-7 细胞的 IC 值为 32.51 ± 0.70 μg/ml,对 MDA-MB-231 癌细胞的 IC 值为 8.53 ± 0.97 μg/ml,表现出细胞毒性活性。通过 ROS 生成、Bcl-2 衰减和 Bax 蛋白诱导发现了内在凋亡途径的诱导。这得到了 caspase-9 的激活、凋亡细胞的增加以及 ΔΨm 的减少的支持。在急性毒性中,SCE 100mg/kg 没有检测到肝或肾毒性的迹象。GC 质量和 NMR 鉴定出生物活性化合物为一种单萜、一种倍半萜、五种脂肪酸、一种邻苯二甲酸酯和两种甾体化合物。

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