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Design, Synthesis and Biological Evaluation of β-Carboline Dimers Based on the Structure of Neokauluamine.基于新考卢胺结构的β-咔啉二聚体的设计、合成及生物学评价
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Autophagy inhibition enhances isorhamnetin‑induced mitochondria‑dependent apoptosis in non‑small cell lung cancer cells.自噬抑制增强异鼠李素诱导的非小细胞肺癌细胞线粒体依赖性凋亡。
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Manzamine alkaloids: isolation, cytotoxicity, antimalarial activity and SAR studies.曼泽明生物碱：分离、细胞毒性、抗疟活性及构效关系研究。
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Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels.自噬通过调节PUMA水平来控制线粒体凋亡的动力学和程度。
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Self-consumption: the interplay of autophagy and apoptosis.自噬：自噬与细胞凋亡的相互作用。
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The marine natural product manzamine A targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells.海洋天然产物马尼拉胺 A 靶向液泡型 ATP 酶并抑制胰腺癌细胞中的自噬作用。
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Chloroquine promotes apoptosis in melanoma cells by inhibiting BH3 domain-mediated PUMA degradation.氯喹通过抑制 BH3 结构域介导的 PUMA 降解促进黑素瘤细胞凋亡。
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二聚体β-咔啉诱导非小细胞肺癌癌细胞中依赖PUMA的凋亡

PUMA-dependent apoptosis in NSCLC cancer cells by a dimeric β-carboline.

作者信息

Chatwichien Jaruwan, Basu Subhasree, Budina-Kolomets Anna, Murphy Maureen E, Winkler Jeffrey D

机构信息

Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States.

The Wistar Institute, Philadelphia, PA 19104, United States.

出版信息

Bioorg Med Chem Lett. 2016 Oct 15;26(20):4884-4887. doi: 10.1016/j.bmcl.2016.09.030. Epub 2016 Sep 13.

DOI:10.1016/j.bmcl.2016.09.030
PMID:27650927
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5464723/
Abstract

Dimeric β-carbolines are cytotoxic against multiple NSCLC cell lines, and we report herein our preliminary studies on the mechanism of action of these dimeric structures. Dimeric β-carboline 1, which is more potent than the corresponding monomer in NSCLC cell lines, is a lysosomotropic agent that inhibits autophagy and mediates cell death by apoptosis, upregulating the pro-apoptotic BH3-only protein PUMA (p53 upregulated modulator of apoptosis) in a dose dependent manner.

摘要

二聚体β-咔啉对多种非小细胞肺癌（NSCLC）细胞系具有细胞毒性，我们在此报告对这些二聚体结构作用机制的初步研究。二聚体β-咔啉1在NSCLC细胞系中比相应单体更具活性，它是一种溶酶体亲和剂，可抑制自噬并通过凋亡介导细胞死亡，以剂量依赖方式上调仅含BH3结构域的促凋亡蛋白PUMA（p53上调凋亡调节因子）。