title: Pinus densiflora leaf essential oil induces apoptosis via ROS generation             and activation of caspases in YD-8 human oral cancer cells.
abstract: The leaf of Pinus (P.) densiflora, a pine tree widely distributed in Asian countries, has been used as a traditional medicine. In the present study, we investigated the anticancer activity of essential oil, extracted by steam distillation, from the leaf of P. densiflora in YD-8 human oral squamous cell carcinoma (OSCC) cells. Treatment of YD-8 cells with P. densiflora leaf essential oil (PLEO) at 60 µg/ml for 8 h strongly inhibited proliferation and survival and induced apoptosis. Notably, treatment with PLEO led to generation of ROS, activation of caspase-9, PARP cleavage, down-regulation of Bcl-2, and phosphorylation of ERK-1/2 and JNK-1/2 in YD-8 cells. Treatment with PLEO, however, did not affect the expression of Bax, XIAP and GRP78. Importantly, pharmaco-logical inhibition studies demonstrated that treatment with vitamin E (an anti-oxidant) or z-VAD-fmk (a pan-caspase inhibitor), but not with PD98059 (an ERK-1/2 inhibitor) or SP600125 (a JNK-1/2 inhibitor), strongly suppressed PLEO-induced apoptosis in YD-8 cells and reduction of their survival. Vitamin E treatment further blocked activation of caspase-9 and Bcl-2 down-regulation induced by PLEO. Thus, these results demonstrate firstly that PLEO has anti-proliferative, anti-survival and pro-apoptotic effects on YD-8 cells and the effects are largely due to the ROS-dependent activation of caspases.
authors.affiliation: Department of Medical Genetic Engineering, Keimyung University                     School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Jeong-Rang
authors.initials: JR
authors.lastname: Jo
authors.forename: Ju Sung
authors.initials: JS
authors.lastname: Park
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Park
authors.forename: Young Zoo
authors.initials: YZ
authors.lastname: Chae
authors.forename: Gyu-Hee
authors.initials: GH
authors.lastname: Lee
authors.forename: Gy-Young
authors.initials: GY
authors.lastname: Park
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009822:Oils, Volatile / Q000494:pharmacology*; D028223:Pinus / Q000737:chemistry*; D018515:Plant Leaves / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D009822:Oils, Volatile; D017382:Reactive Oxygen Species; D020169:Caspases
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