期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms18102105
关键词
curcumin; endoplasmic reticulum stress; unfolded protein response; mitochondrial depolarization; caspase-3; apoptosis
资金
- National Research, Development and Innovation Office (NKFI), Hungary [GINOP-2.3.2-15-2016-00030, GINOP-2.3.2-15-2016-00001]
- Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00139/17/8]
Achiral Mannich-type curcumin analogs have been synthetized and assayed for their cytotoxic activity. The anti-proliferative and cytotoxic activity of curcuminoids has been tested on human non-small-cell lung carcinoma (A549), hepatocellular carcinoma (HepG2) and pancreatic cancer cell line (PANC-1). Based on the highest anti-proliferative activity nine drug candidates were further tested and proved to cause phosphatidylserine exposure as an early sign of apoptosis. Curcumin analogs with the highest apoptotic activity were selected for mechanistic studies in the most sensitive PANC-1 cells. Cytotoxic activity was accompanied by cytostatic effect since curcumin and analogs treatment led to G(0)/G(1) cell cycle arrest. Moreover, cytotoxic effect could be also detected via the accumulation of curcuminoids in the endoplasmic reticulum (ER) and the up-regulation of ER stress-related unfolded protein response (UPR) genes: HSPA5, ATF4, XBP1, and DDIT3. The activated UPR induced mitochondrial membrane depolarization, caspase-3 activation and subsequent DNA breakdown in PANC-1 cells. Achiral curcumin analogs, C509, C521 and C524 possessed superior, 40-times more potent cytotoxic activity compared to natural dihydroxy-dimetoxycurcumin in PANC-1 cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据