1. Perifosine sensitizes UVB-induced apoptosis in skin cells: new implication of skin cancer prevention?
- Author
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Ji C, Yang YL, Yang Z, Tu Y, Cheng L, Chen B, Xia JP, Sun WL, Su ZL, He L, and Bi ZG
- Subjects
- Cells, Cultured, Ceramides biosynthesis, Dose-Response Relationship, Drug, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Extracellular Signal-Regulated MAP Kinases metabolism, Humans, Phosphorylcholine pharmacology, Proto-Oncogene Proteins c-akt antagonists & inhibitors, Proto-Oncogene Proteins c-akt metabolism, Reactive Oxygen Species metabolism, Signal Transduction drug effects, Structure-Activity Relationship, Apoptosis drug effects, Apoptosis radiation effects, Phosphorylcholine analogs & derivatives, Skin cytology, Skin drug effects, Skin Neoplasms prevention & control, Ultraviolet Rays
- 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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