Effects of α-pinene extracted from pine needle on expression of miR-221 and its potential target genes in human hepatocellular carcinoma cells

Abstract

To investigate the anti-hepatoma mechanism of α-pinene, HepG2 cell was treated with α-pinene and the change of cell cycle was examined by flow cytometry. The expression of miR-221, which was related the regulation of G₂/M phase, was detected by quantitative Real-time PCR. Meanwhile, TargetScan and other online bioinformatics methods were used to analyze and predict the target genes of miR-221, then the expression level of related target genes were detected by quantitative Real-time PCR. The results showed that α-pinene inhibited the proliferation of HepG2 cells in dose-dependent manner. It was also proved that HepG2 cells were arrested at G₂/M phase by α-pinene (P<0.05). The expression of miR-221 was down-regulated in α-pinene treated HepG2 cell. The bioinformatics analysis showed that CDKN1B/P27 and CDKN1C/P57 may be the protential targets of miR-221 and both of them were significantly up-regulated（P<0.001,P<0.05）by α-pinene treatment. According to these results, it was believed that α-pinene may inhibit the proliferation of hepatocellular carcinoma cells through arrest the cell at G₂/M phase, which may be associated with the down-regulate of the miR-221 expression and up-regulate of the CDKN1B/P27 and CDKN1C/P57 expression.

Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature

“…Other studies have also suggested the use of α-pinene as a potent antitumor drug. Yang et al measured the inhibitory properties of α-pinene on human hepatocellular carcinoma (HepG2) cells propagation, and found cell cycle arrest at G 2 /M phase, which seemed to be associated with down-regulation of miR-221 expression and up-regulation of CDKN1B/P27 and CDKN1C/P57 expression [37]. The effect of α-pinene on cell cycle regulation in HepG2 cells was also investigated and developed as a promising chemotherapeutic drug for administration in hepatocellular carcinoma [38].…”

Two Worlds Colliding: The Interplay Between Natural Compounds and Non-Coding Transcripts in Cancer Therapy

“…α-pinene is an isomer of pinene, a monoterpene found in the resin of coniferous plants. Xu Q. et al (2018) and Yang J. B. et al (2016) showed that α-pinene induced G2/M phase cell cycle arrest and inhibited miR-221 expression with downstream up-regulation of CDKN1B/P27 and down-regulation of CDKN1C/P57 in HCC cells.…”