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Int. J. Mol. Sci. 2018, 19(9), 2649; https://doi.org/10.3390/ijms19092649

Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway

1
Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan
2
College of Medicine, Chang Gung University, Guishan Dist., Taoyuan City 33303, Taiwan
3
Department of Nursing, Division of Basic Medical Sciences, and Chronic Diseases and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan
4
Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
5
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Zuoying Dist., Kaohsiung City 81362, Taiwan
6
Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Zuoying Dist., Kaohsiung City 81362, Taiwan
7
Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City 33303, Taiwan
8
Division of Neurosurgery, Department of Surgery, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan
9
Department of Respiratory Care, Chang Gung University of Science and Technology, Puzi City, Chiayi County 61363, Taiwan
10
Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Guishan Dist., Taoyuan City 33303, Taiwan
11
Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung Memorial Hospital, Puzi City, Chiayi County 61363, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 13 August 2018 / Revised: 3 September 2018 / Accepted: 4 September 2018 / Published: 6 September 2018
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Malignant melanoma is developed from pigment-containing cells, melanocytes, and primarily found on the skin. Malignant melanoma still has a high mortality rate, which may imply a lack of therapeutic agents. Lakoochin A, a compound isolated from Artocarpus lakoocha and Artocarpus xanthocarpus, has an inhibitory function of tyrosinase activity and melanin production, but the anti-cancer effects are still unclear. In the current study, the therapeutic effects of lakoochin A with their apoptosis functions and possible mechanisms were investigated on A375.S2 melanoma cells. Several methods were applied, including 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT), flow cytometry, and immunoblotting. Results suggest that lakoochin A attenuated the growth of A375.S2 melanoma cells through an apoptosis mechanism. Lakoochin A first increase the production of cellular and mitochondrial reactive oxygen species (ROSs); mitochondrial ROSs then promote mitogen-activated protein kinases (MAPKs) pathway activation and raise downstream apoptosis-related protein and caspase expression. This is the first study to demonstrate that lakoochin A, through ROS-MAPK, apoptosis-related proteins, caspases cascades, can induce melanoma cell apoptosis and may be a potential candidate compound for treating malignant melanoma. View Full-Text
Keywords: lakoochin A; mitochondria; melanoma cells; MAPKs; pro-oxidation; apoptosis lakoochin A; mitochondria; melanoma cells; MAPKs; pro-oxidation; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Peng, K.-T.; Chiang, Y.-C.; Ko, H.-H.; Chi, P.-L.; Tsai, C.-L.; Ko, M.-I.; Lee, M.-H.; Hsu, L.-F.; Lee, C.-W. Mechanism of Lakoochin A Inducing Apoptosis of A375.S2 Melanoma Cells through Mitochondrial ROS and MAPKs Pathway. Int. J. Mol. Sci. 2018, 19, 2649.

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