Effect of honokiol and 5-FU on non-melanoma skin cancer cells

Background: Recent reports have indicated that honokiol can suppress tumor growth and induce apoptosis in a number of tumors. This work aimed to investigate the effect of honokiol alone or in combination with the anti-cancer drug 5-fluorouracil (5-FU), on immortalized and cancerous skin cells. Methods: Two cell lines were used in this study: HaCaT, immortalized human keratinocytes, and TE 354.T, basal cell carcinoma. The effect of honokiol on cell proliferation was measured by methylene blue assay. Apoptosis was evaluated by cell cycle analysis and annexin-V FITC (fluorescein isothiocyanate) apoptosis detection kit. FITC skin penetration from honokiol solution was tested in Franz diffusion cells and viewed by CLSM. Results: Honokiol at a concentration of 10 μg/mL efficiently inhibited cell proliferation and induced cell apoptosis. The combination of honokiol and 5-FU resulted in significantly increased inhibition of cell proliferation and enhanced cell apoptosis in HaCaT keratinocytes. Additionally, enhanced skin penetration of the fluorescent probe, FITC, was observed from honokiol solution. Conclusion: The results of this work suggest that the drug combination of 5-FU and honokiol is efficient in inhibition of cell growth and induction of apoptosis and should therefore be further investigated for improved topical treatment of skin cancer.