Anti-proliferative effects of cinnamaldehyde on human hepatoma cell lines

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• 作者：Lea-Yea Chuang^a ; Jinn-Yuh Guh^b ; Louis Kuoping Chao^c ; Ying-Chen Lu^d ; Jean-Yu Hwang^e ; Yu-Lin Yang^d ; Tsan-Hwang Cheng^d ; Wan-Yu Yang^d ; Ying-Jiun Chien^d ; Jau-Shyang Huang^d ; ^{jaushyang12@hotmail.com}
• 关键词：HCC ; hepatocellular carcinoma ; JAK2 ; Janus kinase 2 ; LDH ; lactate dehydrogenase ; PCNA ; proliferative cell nuclear antigen ; SOCS ; suppressor of cytokine signalling ; STATs ; signal transducers and activators of transcription ; STS ; staurosporine
• 刊名：Food Chemistry
• 出版年：2012
• 期刊代码：48_03088146
• 类别：abs
• 出版时间：15 August, 2012
• 卷：133
• 期：4
• 页码：1603-1610
• 文件大小：645 K

摘要

Cinnamaldehyde has been shown to exert diverse health benefits on humans. We investigated the molecular effects of cinnamaldehyde on the growth regulation mechanism and the Janus kinase-signal transducers and activators of the transcription (JAK-STAT) signalling pathway in human hepatoma cells. We found that cinnamaldehyde caused inhibition of cellular mitogenesis, partly by promoting apoptosis in two human hepatoma cancer cell lines - HepG2 and Hep3B. Amplified changes in caspase 3 activity, Bcl-2 protein expression, and mitochondrial cytochrome c release were displayed in cinnamaldehyde treatments in these cells. The ability of cinnamaldehyde to induce growth arrest was also verified by the observation that it significantly decreased the protein levels of cyclin D1 and proliferative cell nuclear antigen (PCNA) but increased the protein levels of p27^Kip1 and p21^Waf1/Cip1. Especially, the JAK2-STAT3/STAT5 signalling pathway was markedly blocked by cinnamaldehyde in human hepatoma cells. Suppressor of cytokine signalling 1 (SOCS1) and SOCS3 expressions were slightly activated by cinnamaldehyde. The specific JAK2 inhibitor, AG490, significantly prevented the phosphorylation of STAT3 and STAT5 proteins and enhanced the effect of cinnamaldehyde-inhibited cellular mitogenesis. Hence, these results suggest that cinnamaldehyde has a potent inhibitory effect against human hepatoma cell growth, and the JAK2-STAT3/STAT5 and that the apoptotic pathways may be important targets of cinnamaldehyde.