title: Perifosine sensitizes UVB-induced apoptosis in skin cells: new implication of skin cancer prevention?
abstract: We demonstrate here that a relative low dose of perifosine significantly enhanced UVB-induced apoptosis in skin cells (keratinocytes and fibroblasts), associated with a significant increase of reactive oxygen species (ROS) and ceramide production as well as multiple perturbations of diverse cell signaling pathways, shifting to a significant pro-apoptosis outcomes. Perifosine inhibited UVB-induced pro-survival Akt/mammalian target of rapamycin (mTOR) and ERK activation, while facilitating pro-apoptotic AMP-activated protein kinas (AMPK), c-Jun-NH(2)-kinase (JNK), and p53 activation; these signaling changes together promoted a striking increase in skin cell apoptosis and a significantly reduced amount of DNA damages. Our results suggest that perifosine may represent a novel skin cancer prevention strategy.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China. surpassing_ji@yahoo.com.cn
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.forename: Yan-li
authors.initials: YL
authors.lastname: Yang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Tu
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Ji-ping
authors.initials: JP
authors.lastname: Xia
authors.forename: Wei-ling
authors.initials: WL
authors.lastname: Sun
authors.forename: Zhong-lan
authors.initials: ZL
authors.lastname: Su
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Bi
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured; D002518:Ceramides / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000166:cytology* / Q000187:drug effects*; D012878:Skin Neoplasms / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
chemical_list: D002518:Ceramides; D017382:Reactive Oxygen Species; D010767:Phosphorylcholine; C105905:perifosine; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases