Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: development of topical formulation.

Abstract

To develop newer and more effective chemopreventive agents for skin cancer, we assessed the effect of honokiol, a phytochemical from the Magnolia plant, on ultraviolet (UV) radiation-induced skin tumorigenesis using the SKH-1 hairless mouse model. Topical treatment of mice with honokiol in a hydrophilic cream-based topical formulation before or after UVB (180 mJ/cm(2)) irradiation resulted in a significant protection against photocarcinogenesis in terms of tumor multiplicity (28-60%, P < 0.05 to <0.001) and tumor volume per tumor-bearing mouse (33-80%, P < 0.05 to 0.001, n = 20). Honokiol also inhibited and delayed the malignant progression of papillomas to carcinomas. To investigate the in vivo molecular targets of honokiol efficacy, tumors and tumor-uninvolved skin samples from the tumor-bearing mice were analyzed for inflammatory mediators, cell cycle regulators and survival signals using immunostaining, western blotting and enzyme-linked immunosorbent assay. Treatment with honokiol significantly inhibited UVB-induced expression of cyclooxygenase-2, prostaglandin E(2) (P < 0.001), proliferating cell nuclear antigen and proinflammatory cytokines, such as tumor necrosis factor-α (P < 0.001), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.001) in the skin as well as in skin tumors. Western blot analysis revealed that honokiol: (i) inhibited the levels of cyclins D1, D2 and E and associated cyclin-dependent kinases (CDKs)2, CDK4 and CDK6, (ii) upregulated Cip/p21 and Kip/p27 and (iii) inhibited the levels of phosphatidylinositol 3-kinase and the phosphorylation of Akt at Ser(473) in UVB-induced skin tumors. Together, our results indicate that honokiol holds promise for the prevention of UVB-induced skin cancer by targeting inflammatory mediators, cell cycle regulators and cell survival signals in UVB-exposed skin.

• Authors: Mudit Vaid, Som D Sharma, Santosh K Katiyar
• Journal: Carcinogenesis (Carcinogenesis) Vol. 31 Issue 11 Pg. 2004-11 (Nov 2010) ISSN: 1460-2180 [Electronic] England
• PMID: 20823108 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anti-Infective Agents
• Biphenyl Compounds
• Drugs, Chinese Herbal
• Inflammation Mediators
• Lignans
• honokiol
• Cyclooxygenase 2
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Cyclin-Dependent Kinases

Topics

• Administration, Topical
• Animals
• Anti-Infective Agents (therapeutic use)
• Biphenyl Compounds (therapeutic use)
• Blotting, Western
• Cell Cycle (radiation effects)
• Cell Transformation, Neoplastic (drug effects, radiation effects)
• Cyclin-Dependent Kinases (metabolism)
• Cyclooxygenase 2 (metabolism)
• Drugs, Chinese Herbal
• Enzyme-Linked Immunosorbent Assay
• Female
• Immunoenzyme Techniques
• Inflammation Mediators (metabolism, radiation effects)
• Lignans (therapeutic use)
• Magnolia (chemistry)
• Mice
• Mice, Hairless
• Papilloma (metabolism, pathology, prevention & control)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation (radiation effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (radiation effects)
• Skin Neoplasms (metabolism, pathology, prevention & control)
• Ultraviolet Rays (adverse effects)