Perillyl alcohol causes G1 arrest through p15INK4b and p21WAF1/Cip1 induction

被引：25

作者：

Koyama, Makoto ^{[1
]}

Sowa, Yoshihiro ^{[1
]}

Hitomi, Toshiaki ^{[1
]}

Iizumi, Yosuke ^{[1
]}

Watanabe, Motoki ^{[1
]}

Taniguchi, Tomoyuki ^{[1
]}

Ichikawa, Masami ^{[1
]}

Sakai, Toshiyuki ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Mol Targeting Canc Prevent, Grad Sch Med Sci, Kamigyo Ku, Kyoto 6028566, Japan

来源：

ONCOLOGY REPORTS | 2013年 / 29卷 / 02期

关键词：

perillyl alcohol; G1; arrest; retinoblastoma protein; p15(INK4b); p21(WAF1/Cip1); CELL-CYCLE ARREST; PHASE-II TRIAL; NSC; 641066; INHIBITOR; CANCER; P21; PROTEIN; FAMILY; AGENT;

D O I：

10.3892/or.2012.2167

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The monoterpene perillyl alcohol (POH) is a naturally occurring compound derived from citrus fruits, mint and herbs. It exhibited chemotherapeutic potential against various malignant tumors in preclinical models and is currently being tested in clinical trials in patients with refractory advanced cancers. POH inhibits cellular proliferation at the G1 phase of the cell cycle in vitro. However, the molecular mechanisms responsible for this effect have not been sufficiently elucidated. Here we showed that 1.0 mM POH upregulates p15(INK4b) and p21(WAF1/Cip1), resulting in hypophosphorylation of the retinoblastoma (RB) protein and subsequent G1 arrest in human immortalized keratinocyte HaCaT cells. The induction of p15(INK4b) was mediated through its promoter, but that of p21(WAF1/Cip1) was not. The small interfering RNA (siRNA) of either p15(INK4b) or p21(WAF1/Cip1) significantly attenuated the increase in the G1 cell population caused by POH. The induction of p15(INK4b) and p21(WAF1/Cip1) and subsequent G1 arrest by POH was also observed in other cancer cell lines. These results suggest that the induction of p15(INK4b) as well as p21(WAF1/Cip1) is associated with the antiproliferative effect of POH.

引用

页码：779 / 784

页数：6

共 40 条

[1] p21 in cancer: intricate networks and multiple activities [J].