Effects of alpha-santalol on proapoptotic caspases and p53 expression in UVB irradiated mouse skin.
BACKGROUND
Cancer chemoprevention by naturally occurring agents, especially phytochemicals, minerals and vitamins has shown promising results against various malignancies in a number of studies both under in vitro and in vivo conditions. One such phytochemical, alpha-santalol, a major component of sandalwood oil, is effective in preventing skin cancer in both chemically and UVB-induced skin cancer development in CD-1, SENCAR and SKH-1 mice; however, the mechanism of its efficacy is not fully understood. The objective of the present investigation was to study the effects of alpha-santalol on apoptosis proteins and p53 in UVB-induced skin tumor development in SKH-1 mice to elucidate the mechanism of action.


METHODS
Female SKH-1 mice were divided into two groups: Group 1, which served as control received topical application of acetone (0.1 ml) one hour before UVB treatment; Group 2 received alpha-santalol (0.1 ml, 5% w/v in acetone, topical) one hour prior to UVB treatment. UVB-induced promotion was continued for 30 weeks.


RESULTS
Pre-treatment with alpha-santalol one hour prior to UVB exposure significantly (p < 0.05) reduced tumor incidence and multiplicity, and resulted in a significant (p < 0.05) increase in apoptosis proteins, caspase-3 and -8 levels and tumor suppressor protein, p53.


CONCLUSIONS
These results suggest that alpha-santalol prevents skin cancer development by inducing proapoptotic proteins via an extrinsic pathway and increasing p53.
Arasada
Bhanu L
BL
Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
Bommareddy
Ajay
A
Zhang
Xiaoying
X
Bremmon
Kathryn
K
Dwivedi
Chandradhar
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D005260:Female; D051379:Mice; D018632:Mice, Inbred SENCAR; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000517:prevention & control*; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014466:Ultraviolet Rays
D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53; C043206:santalol; D053148:Caspase 3; D053181:Caspase 8