Lupeol induces p53 and cyclin-B-mediated G2/M arrest and targets apoptosis through activation of caspase in mouse skin.
Lupeol, present in fruits and medicinal plants, is a biologically active compound that has been shown to have various pharmacological properties in experimental studies. In the present study, we demonstrated the modulatory effect of lupeol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced alterations on cell proliferation in the skin of Swiss albino mice. Lupeol treatment showed significant (p < 0.05) preventive effects with marked inhibition at 48, 72, and 96 h against DMBA-mediated neoplastic events. Cell-cycle analysis showed that lupeol-induced G2/M-phase arrest (16-37%) until 72 h, and these inhibitory effects were mediated through inhibition of the cyclin-B-regulated signaling pathway involving p53, p21/WAF1, cdc25C, cdc2, and cyclin-B gene expression. Further lupeol-induced apoptosis was observed, as shown by an increased sub-G1 peak (28%) at 96 h, with upregulation of bax and caspase-3 genes and downregulation of anti-apoptotic bcl-2 and survivin genes. Thus, our results indicate that lupeol has novel anti-proliferative and apoptotic potential that may be helpful in designing strategies to fight skin cancer.
Nigam
Nidhi
N
Proteomics Laboratory, Indian Institute of Toxicology Research, Council of Scientific & Industrial Research, P.O. Box 80, M.G. Marg, Lucknow-226001, UP, India.
Prasad
Sahdeo
S
George
Jasmine
J
Shukla
Yogeshwer
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000096:biosynthesis* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D019926:Cyclin B / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D053978:Pentacyclic Triterpenes; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000517:prevention & control*; D014158:Transcription, Genetic / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000094042:Lupanes
D000970:Antineoplastic Agents; D053148:Caspase 3; D019926:Cyclin B; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; C010480:lupeol; D000094042:Lupanes