Abstract 3809: Effects of honokiol on UACC-62 and SKMEL-2 melanoma cell lines

Abstract

Abstract Honokiol is a plant lignan extracted from the magnolia bark tree, previous studies from our laboratory showed its chemopreventive effects in a UVB-induced skin cancer model, as well as pro-apoptotic effects in A431 squamous cancer cell line. Studies from other groups have reported antineoplastic effects in different cancer models as well. In this study, the antineoplastic effects of honokiol were evaluated in vivo and in vitro against UACC-62 cell line that harbors mutated BRAF, CDK4i, PTEN and against SKMEL-2 cell line that presents NRAF, and TP53 mutated genes. For the in vivo studies, nude male mice were injected subcutaneously with 5x106 UACC-62 or SKMEL-2 cells. The next day animals were randomized into control and treatment groups, each group containing 20 animals. The control group received 250 αl of sesame oil intraperitoneally (IP), the treatment groups received honokiol dissolved in sesame oil; 1.25 mg (IP) in the UACC-62 group and 50 mg/kg (IP) in the SKMEL-2 injected mice. Animals were treated three times a week, for 5-7 weeks. Tumors’ incidence, multiplicity and volume were recorded every three days, mice's weights and external signs of toxicity were also closely monitored. Tumor tissues were collected for histopathology, Western blots, and PCR arrays. For the in vitro studies, both cell lines were evaluated for cell viability, proliferation, apoptosis by TUNEL assay, cell cycle arrest by propidium iodide staining, and Western blots for proteins expressions. Honokiol treatment significantly reduced (p<0.05) tumor volumes in both xenograft experiments. No evident signs of toxicity were observed in the honokiol treated animals. In both cell lines, honokiol significantly decreased (p<0.05) cell viability and proliferation, honokiol caused cell cycle arrest in Go/G1 phase in UACC-62 cell line, while it caused accumulation of cells in the G2/M phase in SKMEL-2 cell line; honokiol significantly increased the DNA fragmentation in both cell lines. Honokiol strongly decreased the expressions of cyclin D1, cyclin D2 and cyclin B1 while increasing the cleavage of caspase 3, caspase 8, caspase 9 and PARP in both cell lines. In UACC-62 honokiol decreased the expressions of CDK2, CDK4, cyclin E, cdc2p34 and p21. In SKMEL-2, honokiol decreased the expression of CDK4, PCNA and increased the expression of p21. These findings suggest that honokiol is a good candidate for further studies as a treatment for malignant melanoma. This work is supported by a Translational Cancer Center Research Grant, funded as 2010 Research Initiative Center by the State of South Dakota. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3809. doi:1538-7445.AM2012-3809