伊拉霉素 E 是一种海洋放线菌的天然产物，通过内质网应激-CHOP-Bcl-2 途径部分抑制三阴性乳腺癌。

Ilamycin E, a natural product of marine actinomycete, inhibits triple-negative breast cancer partially through ER stress-CHOP-Bcl-2.

机构信息

Department of Laboratory Medicine & Central Laboratory, Southern Medical University Affiliated Fengxian Hospital, Shanghai, China, 201499.

Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China, 650223.

出版信息

Int J Biol Sci. 2019 Jun 10;15(8):1723-1732. doi: 10.7150/ijbs.35284. eCollection 2019.

DOI:10.7150/ijbs.35284

PMID:31360114

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6643221/

Abstract

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women in the worldwide. Triple-negative breast cancer (TNBC) has a poor clinical outcome. The antitumor efficacy of Ilamycins, natural products with anti-tuberculosis activity isolated from deep sea-derived Streptomyces atratus, in TNBC has not been investigated, and the mechanisms remain elusive. Here, we demonstrated that Ilamycin-E, but not -F, decreases cell viability, inhibits G1/S cell cycle progression, and promotes apoptosis in the TNBC cell lines HCC1937 and MDA-MB-468. Ilamycin E promotes apoptosis via activation of endoplasmic reticulum (ER) stress, increasing the expression of CHOP, and down-regulating the expression of anti-apoptotic protein Bcl-2. Depletion of CHOP or overexpression of Bcl2 significantly rescued Ilamycin E-induced apoptosis. These findings indicate that Ilamycin E has anti-cancer activity in TNBC.

摘要

乳腺癌是全世界范围内最常见的癌症，也是女性癌症死亡的主要原因。三阴性乳腺癌（TNBC）的临床预后较差。伊拉霉素是从深海来源的灰色链霉菌中分离出的具有抗结核活性的天然产物，其在 TNBC 中的抗肿瘤疗效尚未得到研究，其机制仍不清楚。在这里，我们证明伊拉霉素-E，但不是-F，可降低细胞活力，抑制 G1/S 细胞周期进程，并促进 TNBC 细胞系 HCC1937 和 MDA-MB-468 中的细胞凋亡。伊拉霉素 E 通过激活内质网（ER）应激促进细胞凋亡，增加 CHOP 的表达，并下调抗凋亡蛋白 Bcl-2 的表达。CHOP 的耗竭或 Bcl2 的过表达可显著挽救伊拉霉素 E 诱导的细胞凋亡。这些发现表明伊拉霉素 E 在 TNBC 中具有抗癌活性。