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海洋物种次生代谢产物对前列腺癌细胞的抗增殖活性

The Anti-Proliferative Activity of Secondary Metabolite from the Marine sp. against Prostate Cancer Cells.

作者信息

Lin Hung-Yu, Lin Yong-Shiou, Shih Shou-Ping, Lee Sung-Bau, El-Shazly Mohamed, Chang Ken-Ming, Yang Yu-Chen S H, Lee Yi-Lun, Lu Mei-Chin

机构信息

School of Medicine, College of Medicine, I-SHOU University, Division of Urology, Department of Surgery, E-Da Cancer & E-Da Hospital, Kaohsiung 824, Taiwan.

Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung 944, Taiwan.

出版信息

Life (Basel). 2021 Dec 16;11(12):1414. doi: 10.3390/life11121414.

Abstract

Many active substances from marine organisms are produced by symbiotic microorganisms such as bacteria, fungi, and algae. Secondary metabolites from marine actinomycetes exhibited several biological activities and provided interesting drug leads. This study reported the isolation of Lu01-M, a secondary metabolite from the marine actinomycetes sp., with potent anti-proliferative activity against prostate cancers. Lu01-M blocked cell proliferation with IC values of 1.03 ± 0.31, 2.12 ± 0.38, 1.27 ± 0.25 μg/mL in human prostate cancer PC3, DU145, and LNCaP cells, respectively. Lu01-M induced cytotoxic activity through multiple mechanisms including cell apoptosis, necroptosis, autophagy, ER stress, and inhibiting colony formation and cell migration. Lu01-M induced cell cycle arrest at the G2/M phase and DNA damage. However, the activity of autophagy induced survival response in cancer cells. Our findings suggested that Lu01-M holds the potential to be developed as an anti-cancer agent against prostate cancers.

摘要

许多来自海洋生物的活性物质是由共生微生物如细菌、真菌和藻类产生的。海洋放线菌产生的次级代谢产物具有多种生物活性,并提供了有趣的药物先导物。本研究报道了从海洋放线菌中分离出一种次级代谢产物Lu01-M,它对前列腺癌具有强大的抗增殖活性。Lu01-M在人前列腺癌PC3、DU145和LNCaP细胞中阻断细胞增殖,其IC值分别为1.03±0.31、2.12±0.38、1.27±0.25μg/mL。Lu01-M通过多种机制诱导细胞毒性活性,包括细胞凋亡、坏死性凋亡、自噬、内质网应激,并抑制集落形成和细胞迁移。Lu01-M诱导细胞周期停滞在G2/M期并造成DNA损伤。然而,自噬活性在癌细胞中诱导了存活反应。我们的研究结果表明,Lu01-M有潜力被开发成为一种抗前列腺癌的抗癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edce/8706809/0fe74692a400/life-11-01414-g001.jpg

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