Antineoplastic Effects of Honokiol on Melanoma.

Ruth Guillermo-Lagae,Radhey S Kaushik,Jonathan Stevens,Emily Zoelle,Sreevidya Santha,Chandradhar Dwivedi,Milton Thomas

doi:10.1155/2017/5496398

Abstract

Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks. In vitro honokiol treatment caused significant decrease in cell viability, proliferation, cell cycle arrest, increased apoptosis, and modulation of apoptotic and cell cycle regulatory proteins. Honokiol caused an accumulation of cells in the G2/M phase of the cell cycle in SKMEL-2 and G0/G1 phase in UACC-62 cells. An elevated level of caspases and PARP were observed in both cell lines treated with honokiol. A decrease in the expression of various cell cycle regulatory proteins was also observed in honokiol treated cells. Honokiol caused a significant reduction of tumor growth in SKMEL-2 and UACC-62 melanoma xenografts. These findings suggest that honokiol is a good candidate for further studies as a possible treatment for malignant melanoma.

Highlights

According to the American Cancer Society, melanoma will cause 76,380 new cases and 10,130 deaths in 2016
Primary antibodies for cyclin D1, cyclin D2, cyclin E, cyclin dependent kinase (CDK)-2, CDK-4, cyclin A, Cdc2p34, proliferating cell nuclear antigen (PCNA), caspase 3, anti-mouse IgG horseradish peroxidase-linked and anti-rabbit IgG horseradish peroxidase-linked secondary antibodies, and nitrocellulose membranes were purchased from Santa Cruz Biotechnology (Santa Cruz, CA)
Honokiol Treatment Decreased Cell Viability in SKMEL-2 and UACC-62 Cells. Both SKMEL-2 and UACC-62 cells were treated with DMSO or varying concentrations (0–100 μM) of honokiol for 12, 24, 48, and 72 h and cell viability was determined by MTT assay

Summary

Introduction

According to the American Cancer Society, melanoma will cause 76,380 new cases and 10,130 deaths in 2016 Much attention has been given to phytochemicals. They are being investigated for the prevention and treatment of cancer. One of those phytochemicals is honokiol (C18H18O2, MW 266.33), which is a naturally occurring biphenol isolated from the bark and seed cones of Magnolia officinalis [1, 2]. Studies have demonstrated multiple pharmacological properties of honokiol such as antioxidant [3], antiinflammatory [4], and central nervous system depressant effects [5, 6]

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Conclusion