6-C-(E-phenylethenyl)naringenin induces cell growth inhibition and   cytoprotective autophagy in colon cancer cells

doi:10.1016/j.ejca.2016.09.001

CORC > 北京大学 > 工学院

	6-C-(E-phenylethenyl)naringenin induces cell growth inhibition and cytoprotective autophagy in colon cancer cells
	Zhao, Yueliang ; Fan, Daming ; Ru, Beibei ; Cheng, Ka-Wing ; Hu, Shuting ; Zhang, Jiangwen ; Li, Edmund T. S. ; Wang, Mingfu
刊名	EUROPEAN JOURNAL OF CANCER
	2016
关键词	6-CEPN Anticancer Colon cancer RAS METHYLTRANSFERASE ACTIVITY RAS THERAPY APOPTOSIS DEATH MODULATION SIGNATURE PATHWAYS PROTEIN ACID
DOI	10.1016/j.ejca.2016.09.001
英文摘要	6-C-(E-phenylethenyl) naringenin (6-CEPN) is a small molecule found in naringenin fortified fried beef. It has been shown to suppress colon cancer cell proliferation, but the underlying mechanisms are not fully understood. Here we demonstrate that 6-CEPN suppresses tumour cell proliferation through cell cycle arrest in G(1) phase, induces necrotic cell death and autophagy in colon cancer cells. Blockade of autophagy by knockdown of the essential autophagy proteins, Atg7 or beclin-1, resulted in aggravated cell death in response to 6-CEPN treatment. In addition, genome-wide transcriptome expression profiling by RNA-sequencing revealed that 6-CEPN-mediated gene expression pattern was extremely similar to the transcriptome response induced by a RAS inhibitor salirasib (farnesylthiosalicylic acid [FTS; salirasib]). Subsequent molecular biological and biochemical experiments demonstrated that 6-CEPN indeed strongly inhibited RAS activation, leading to the inhibition of the downstream effector pathways c-Raf/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase kinase and phosphoinositide 3-kinase/AKT/mammalian target of rapamycin. More importantly, our computational molecular docking data showed that 6-CEPN could bind to the active site of isoprenylcysteine carboxyl methyltransferase (Icmt), a critical enzyme for the activation of RAS. Icmt activity assay showed that 6-CEPN inhibited its activity significantly. Knockdown of Icmt bysiRNA attenuated 6-CEPN-mediated autophagy and cell death. The present study demonstrates that 6-CEPN induces cell growth inhibition and cytoprotective autophagy in colon cancer cells, at least in part, though inhibition of the Icmt/RAS signalling pathways. (C) 2016 Elsevier Ltd. All rights reserved.; SCI(E); PubMed; ARTICLE; mfwang@hku.hk; 38-50; 68
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/492682]
专题	工学院
推荐引用方式 GB/T 7714	Zhao, Yueliang,Fan, Daming,Ru, Beibei,et al. 6-C-(E-phenylethenyl)naringenin induces cell growth inhibition and cytoprotective autophagy in colon cancer cells[J]. EUROPEAN JOURNAL OF CANCER,2016.
APA	Zhao, Yueliang.,Fan, Daming.,Ru, Beibei.,Cheng, Ka-Wing.,Hu, Shuting.,...&Wang, Mingfu.(2016).6-C-(E-phenylethenyl)naringenin induces cell growth inhibition and cytoprotective autophagy in colon cancer cells.EUROPEAN JOURNAL OF CANCER.
MLA	Zhao, Yueliang,et al."6-C-(E-phenylethenyl)naringenin induces cell growth inhibition and cytoprotective autophagy in colon cancer cells".EUROPEAN JOURNAL OF CANCER (2016).