Time and dose-response effects of honokiol on UVB-induced skin cancer development.
Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.
Department of Pharmaceutical Sciences, South Dakota State University, Brookings, SD 57007, USA.
Ruth F
RF
Guillermo
Chandeshwari
C
Chilampalli
Xiaoying
X
Zhang
David
D
Zeman
Hesham
H
Fahmy
Chandradhar
C
Dwivedi
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005260:Female; D017705:Lignans / Q000627:therapeutic use*; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy* / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects; D014466:Ultraviolet Rays; D015430:Weight Gain / Q000187:drug effects; D000498:Allyl Compounds; D010636:Phenols
D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D017705:Lignans; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols