title: α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.
abstract: This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.
authors.affiliation: Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD, USA.
authors.forename: Sreevidya
authors.initials: S
authors.lastname: Santha
authors.forename: Chandradhar
authors.initials: C
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C043206:santalol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3