Journal
PHYTOMEDICINE
Volume 68, Issue -, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2019.153147
Keywords
Apoptosis; Cell cycle arrest; Epithelial-mesenchymal transition; Gomisin A; Melanoma; Metastasis
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Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [NRF2018R1C1B6002722, NRF-2019R1I1A3A01060998]
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Background: Gomisin A (G.A), a lignan compound extracted from the fruits of Schisandra chinensis, is known to exert anti-tumor effects on hepatocarcinoma and colorectal cancer cells. Suppression of proliferation and metastatic abilities of cancer cells are some effective cancer treatment methods. Purpose: The objective of this study is to investigate the effects of G.A on metastatic melanoma, and the mechanism by which it affects metastatic melanoma. Study design: The anti-proliferative and anti-metastatic effects of G.A were observed in in vitro and in vivo. Methods: WST assay and flow cytometry were conducted to investigate the effect of G.A on proliferation, cell cycle arrest, and apoptosis in metastatic melanoma cell lines. Migration and invasion abilities of G.A-treated melanoma cells were observed by wound healing and invasion assays. Results: G.A (25-100 mu M) decreased the viability of melanoma cells by inducing cell cycle arrest and apoptosis. These anti-proliferative effects of G.A were found to be mediated by AMPK, ERK, and JNK activation. G.A (5-20 mu M) decreased the migration and invasion of melanoma cells by suppressing epithelial-mesenchymal transition (EMT). Consequently, G.A (2-50 mg/kg) inhibited lung metastasis by suppressing EMT and inducing cell cycle arrest and apoptosis in melanoma cells. Conclusion: These results conclude that G.A has the potential to reduce metastatic melanoma through its antiproliferative and anti-metastatic effects.
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