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Biosci Rep. 2018 Dec 11;38(6). pii: BSR20180980. doi: 10.1042/BSR20180980. Print 2018 Dec 21.

α-pinene regulates miR-221 and induces G2/M phase cell cycle arrest in human hepatocellular carcinoma cells.

Author information

1
School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Outer Ring East Road No. 280, Panyu District, Guangzhou 510006, Guangdong Province, China.
2
School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Outer Ring East Road No. 280, Panyu District, Guangzhou 510006, Guangdong Province, China cwq2187@126.com.
3
Guangdong Province Precise Medicine and Big Data Engineering Technology Research Center for Traditional Chinese medicine, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Center, Outer Ring East Road No. 280, Panyu District, Guangzhou 510006, Guangdong Province, China.

Abstract

The naturally occurring compound α-pinene induces cell cycle arrest and antitumor activity. We examined effects of α-pinene on cell cycle regulation in hepatocellular carcinoma cells (HepG2) cells to establish a foundation for its development as a novel treatment for hepatocellular carcinoma (HCC). HepG2 cells treated with α-pinene exhibited dose-dependent growth inhibition as a result of G2/M-phase cell cycle arrest. Cell cycle arrest was associated with down-regulated cyclin-dependent kinase 1 (CDK1) and miR-221 levels and up-regulated levels of CDKN1B/p27, γ-H2AX, phosphorylated ATM, phosphorylated Chk2 and phosphorylated p53. Our observations are consistent with a model in which α-pinene inhibits miR221 expression, which leads to G2/M-phase arrest and activation of CDKN1B/p27-CDK1 and ATM-p53-Chk2 pathways that suppress human hepatoma tumor progression. Additionally, α-pinene was found to trigger oxidative stress and induce apoptosis of HepG2 cells. α-pinene, therefore, represents a potential chemotherapeutic compound for the treatment of HCC.

KEYWORDS:

anti-hepatoma carcinoma; apoptosis; in vitro; miR-221; miRNA; α-pinene

PMID:
30473536
PMCID:
PMC6294613
DOI:
10.1042/BSR20180980
[Indexed for MEDLINE]
Free PMC Article

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