Chemopreventive effects of honokiol on UVB-induced skin cancer development.
BACKGROUND
Skin cancer is the most prevalent of all cancer types and its incidence is expected to increase substantially. Chemoprevention involves the administration of chemical agents to prevent initiation, promotion and/or progression that occurs during neoplastic development. Honokiol, a plant lignan isolated from bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically induced skin cancer development.


OBJECTIVE
The objective of this investigation was to study the chemopreventive effects of honokiol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and to elucidate the possible role of apoptotic proteins involved in the prevention of skin tumor development.


METHODS
Female SKH-1 mice were divided into two groups. Group 1 received acetone (0.2 ml, topical) and Group 2 received honokiol (30 microg in 0.2 ml acetone, topical) one hour before UVB treatment. Tumor initiation and promotion were carried out by UVB radiation (30 mJ/cm(2)/day), 5 days a week for 30 weeks. Tumor counts and mouse weights were taken weekly.


RESULTS
The honokiol-pretreated group exhibited a 45% reduction in tumor multiplicity as compared to the control group. Mechanistic studies showed the possible involvement of caspase-3, caspase-8, caspase-9, poly (ADP-ribose) polymerase (PARP) and p53 activation (p<0.05) leading to the induction of DNA fragmentation and apoptosis.


CONCLUSIONS
Pretreatment with honokiol, at concentrations in micrograms per application compared with milligram applications of other potential chemopreventive agents, prevents UVB-induced skin cancer development, possibly by activating proapoptotic proteins through both intrinsic and extrinsic pathways.
Chilampalli
Shivani
S
Distinguished Professor and Head, Department of Pharmaceutical Sciences, College of Pharmacy-Box 2202 C, 116 A Intramural Building, South Dakota State University, Brookings, SD 57007, USA.
Zhang
Xiaoying
X
Fahmy
Hesham
H
Kaushik
Radhey S
RS
Zeman
David
D
Hildreth
Michael B
MB
Dwivedi
Chandradhar
C
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012878:Skin Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays; D000498:Allyl Compounds; D010636:Phenols
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D020169:Caspases; D017705:Lignans; D016159:Tumor Suppressor Protein p53; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols