Chemopreventive effects of alpha-santalol on skin tumor development in CD-1 and SENCAR mice.
Studies from our laboratory have indicated skin cancer chemopreventive effectsof sandalwood oil in CD-1 mice. The purpose of this investigation was to study the skin cancer chemopreventive effects of alpha-santalol, a principal component of sandalwood oil in CD-1 and SENCAR mice. alpha-Santalol was isolated from sandalwood oil by distillation under vacuum and characterized by nuclear magnetic resonance and gas chromatography-mass spectrometry. Chemopreventive effects of alpha-santalol were determined during initiation and promotion phase in female CD-1 and SENCAR mice. Carcinogenesis was initiated with 7,12-dimethylbenz(a)anthracene and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA). The effects of alpha-santalol treatment on TPA-induced epidermal ornithine decarboxylase (ODC) activity and (3)H-thymidine incorporation in epidermal DNA of CD-1 and SENCAR mice were also investigated. alpha-Santalol treatment during promotion phase delayed the papilloma development by 2 weeks in both CD-1 and SENCAR strains of mice. alpha-Santalol treatment during promotion phase significantly (P < 0.05) decreased the papilloma incidence and multiplicity when compared with control and treatment during initiation phase during 20 weeks of promotion in both CD-1 and SENCAR strains of mice. alpha-Santalol treatment resulted in a significant (P < 0.05) inhibition in TPA-induced ODC activity and incorporation of (3)H-thymidine in DNA in the epidermis of both strains of mice. alpha-Santalol significantly prevents papilloma development during promotion phase of 7,12-dimethylbenz(a)anthracene-TPA carcinogenesis protocol in both CD-1 and SENCAR mice, possibly by inhibiting TPA-induced ODC activity and DNA synthesis. alpha-Santalol could be an effective chemopreventive agent for skin cancer. Additional experimental and clinical studies are needed to investigate the chemopreventive effect of alpha-santalol in skin cancer.
Dwivedi
Chandradhar
C
Department of Pharmaceutical Sciences, South Dakota State University, Brookings 57007, USA. chandradhar_dwivedi@sdstate.edu
Guan
Xiangming
X
Harmsen
Wendy L
WL
Voss
Alison L
AL
Goetz-Parten
Dawn E
DE
Koopman
Erin M
EM
Johnson
Kelly M
KM
Valluri
Hima B
HB
Matthees
Duane P
DP
D000287:Administration, Topical; D000818:Animals; D002273:Carcinogens / Q000009:adverse effects; D018890:Chemoprevention; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015994:Incidence; D051379:Mice; D018632:Mice, Inbred SENCAR; D009955:Ornithine Decarboxylase / Q000187:drug effects; D010212:Papilloma / Q000453:epidemiology / Q000517:prevention & control*; D010938:Plant Oils / Q000008:administration & dosage / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D016387:Women's Health
D002273:Carcinogens; D010938:Plant Oils; D012717:Sesquiterpenes; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; C076763:sandalwood oil