Hemistepsin A Inhibits Cell Proliferation and Induces G0/G1-Phase Arrest, Cellular Senescence and Apoptosis Via the AMPK and p53/p21 Signals in Human Hepatocellular Carcinoma

Biomolecules

Ho Young Suk¹  Ui Wook Hwang²  Su Youn Baek²  Young Woo Kim³ 

[1] Department of Life Sciences, Yeungnam University, 280 Daehak-ro, Gyeongsan, Gyeongsangbuk-do 38541, Korea;Institute for Phylogenomics and Evolution and Institute for Korean Herb-Bio Convergence Promotion, Kyungpook National University, Daegu 41566, Korea;School of Korean Medicine, Dongguk University, Gyeongju 38066, Korea;

关键词: hemistepsin A (HsA);    hepatocellular carcinoma (HCC);    AMP-activated protein kinase (AMPK/mTOR);    p53;    G0/G1 cell cycle arrest;    apoptosis;   

DOI  :  10.3390/biom10050713

来源: DOAJ

【 摘 要 】

Hemistepsin A (HsA), a natural sesquiterpene lactone isolated from Hemistepta lyrata, has been known as a wide range of anti-tumor effects. The aim of this study was to determine whether HsA suppresses hepatocellular carcinoma (HCC) and to figure out the cellular signaling pathways involved in the anti-HCC activities by experiments using the Huh7 cells (a human HCC cell line) and a xenograft HCC model. In this study, HsA completely inhibited HCC cell proliferation, presumably because it induced G0/G1 cell cycle arrest and mitochondrial-related apoptosis. HsA up-regulated p53, p21, cleaved caspase-3 and cleaved PARP (poly (ADP-ribose) polymerase), but reduced cyclin D, CDK6 and Bcl-2 expressions, and it disrupted mitochondrial membrane potential (ΔΨm). Moreover, phosphorylation of AMP-activated protein kinase (AMPK) was increased by HsA as did the resveratrol and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR, positive controls). Inhibition of AMPK by using compound C, a competent inhibitor of AMPK, attenuated the loss of ΔΨm, p53 up-regulation and cellular senescence. The efficacy of HsA to reduce HCC cell proliferation, compared to that of other known anti-HCC agents, appears to be similar or slightly better. The anti-tumor effect of HsA was also determined in mice, showing reduced growth of xenografted tumors with no weight loss. Overall, the results suggest that HsA should be considered as a candidate anti-HCC drug.

【 授权许可】

Unknown