|Induction of apoptosis by D-limonene is mediated by inactivation of Akt in LS174T human colon cancer cells|
Authors: Shu-Sheng Jia, Guang-Peng Xi, Ming Zhang, Yan-Bo Chen, Bo Lei, Xin-Shu Dong, Yan-Mei Yang
Affiliations: Department of Breast Surgery, the Third Affiliated Hospital of Harbin Medical University, Harbin, P.R. China, Cancer Research Institute, Harbin Medical University, Harbin, P.R. China, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China
Published online on: Friday, October 19, 2012
D-limonene is recognized as a potential chemotherapeutic agent, however, the details of this mechanism remain unclear. In this study, we investigated the effects of d-limonene on colon cancer cell viability and its potential mechanism of action in vitro. After 48 h of treatment, d-limonene suppressed the viability of LS174T cells in a dose-dependent manner and caused a dose-dependent apoptotic cell death. D-limonene activated caspase-3 and -9 and PARP cleavage in a dose-dependent manner. Moreover, an increase in Bax protein and cytosol cytochrome c from mitochondria and a decrease in bcl-2 protein were observed following treatment with d-limonene. In addition, d-limonene decreased the levels of p-Akt (Ser473), p-Akt (Thr308) and p-GSK-3β (Ser9), suggesting that d-limonene induced apoptosis via the mitochondrial death pathway and the suppression of the PI3K/Akt pathway.