title: Induction of apoptosis by D-limonene is mediated by inactivation of             Akt in LS174T human colon cancer cells.
abstract: 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.
authors.affiliation: Department of Breast Surgery, the Third Affiliated Hospital of Harbin Medical University, Cancer Research Institute, Harbin Medical University, Harbin, PR China.
authors.forename: Shu-Sheng
authors.initials: SS
authors.lastname: Jia
authors.forename: Guang-Peng
authors.initials: GP
authors.lastname: Xi
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Chen
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.forename: Xin-Shu
authors.initials: XS
authors.lastname: Dong
authors.forename: Yan-Mei
authors.initials: YM
authors.lastname: Yang
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053138:Cyclohexenes / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D000077222:Limonene; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D053138:Cyclohexenes; D019253:Proto-Oncogene Proteins c-bcl-2; D013729:Terpenes; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D000077222:Limonene; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3