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生物碱组分通过内源性凋亡途径对LNCaP和DU 145人前列腺癌细胞的抗癌活性。

Anticancer Activity of Alkaloid Fractions against LNCaP, and DU 145 Human Prostate Cancer Cells through the Intrinsic Apoptotic Pathway.

作者信息

Lotfaliani Mohammadreza, Ghanadian Mustafa, Ayatollahi Seyed Abdulmajid, Aghaei Mahmoud, Kobarfard Farzad

机构信息

Department of Pharmacognosy, School of Pharmacy, Shahid Beheshti University of Medical Science, Tehran, Iran.

Department of Pharmacognosy, School of Pharmacy, Shaheed Sadoughi University of Medical Science and Health Service, Yazd, Iran.

出版信息

Iran J Pharm Res. 2021 Fall;20(4):107-116. doi: 10.22037/ijpr.2021.115462.15382.

Abstract

Prostate cancer is one of the common cancers with a high mortality rate in men. Therefore, there is always a necessity to discover new medications for treatment or alleviating its symptoms. In recent years, anticancer properties of a number of delphinium species were reported, but there is no study on the anticancer effects of () alkaloid contents. Therefore, this survey aimed to check the cytotoxicity and apoptotic properties of alkaloid fractions (DSAFs) against prostate cancer cells. Cytotoxicity was measured by MTT assay. We examined the apoptosis by detecting annexin V-FITC/PI staining, the mitochondrial membrane potential (ΔΨm) disruption, reactive oxygen species (ROS) generation, the activity of caspase-3, and expression of the Bax and Bcl-2 in cancer cells. DSAFs treatment inhibited the growth of LNCaP and DU-145 cells by the increase of apoptotic (Q2+Q3) cells detected by annexin V/PI assay. We found over-generation of intracellular ROS and ΔΨm loss in mitochondrial membrane potential treated cell lines. Attenuation of anti-apoptotic Bcl-2 followed by the increase in pro-apoptotic Bax bands, as well as activation of the caspase-3 enzyme was shown in Western blot analysis. Phytochemical analysis suggested that hetisine type diterpene alkaloids were probably responsible for apoptotic activities. Conclusively, the present study demonstrated that alkaloid content exerted antiproliferative effects against prostate cancer cells by inducing the intrinsic pathway of apoptosis.

摘要

前列腺癌是男性中常见且死亡率较高的癌症之一。因此,一直有必要研发新药物用于治疗或缓解其症状。近年来,有报道称多种翠雀属植物具有抗癌特性,但尚未有关于()生物碱含量抗癌作用的研究。因此,本研究旨在检测翠雀生物碱组分(DSAFs)对前列腺癌细胞的细胞毒性和凋亡特性。通过MTT法测定细胞毒性。我们通过检测膜联蛋白V-FITC/PI染色、线粒体膜电位(ΔΨm)破坏、活性氧(ROS)生成、半胱天冬酶-3活性以及癌细胞中Bax和Bcl-2的表达来检测细胞凋亡。DSAFs处理通过膜联蛋白V/PI检测发现凋亡(Q2+Q3)细胞增加,从而抑制LNCaP和DU-145细胞的生长。我们发现经处理的细胞系中细胞内ROS过度生成且线粒体膜电位的ΔΨm丧失。蛋白质印迹分析显示抗凋亡的Bcl-2减弱,随后促凋亡的Bax条带增加,同时半胱天冬酶-3酶被激活。植物化学分析表明,hetisine型二萜生物碱可能是凋亡活性的原因。总之,本研究表明翠雀生物碱含量通过诱导内源性凋亡途径对前列腺癌细胞发挥抗增殖作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0097/8842624/d94c7156748e/ijpr-20-107-g001.jpg

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