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

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.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Peng KT,Chiang YC,Ko HH,Chi PL,Tsai CL,Ko MI,Lee MH,Hsu LF,Lee CW

doi

10.3390/ijms19092649

subject

Has Abstract

pub_date

2018-09-06 00:00:00

issue

9

issn

1422-0067

pii

ijms19092649

journal_volume

19

pub_type

杂志文章

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