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Fucoidan Induces Apoptosis in A2058 Cells through ROS-exposed Activation of MAPKs Signaling Pathway

Natural Product Sciences 2020년 26권 3호 p.191 ~ 199
Ryu Yea-Seong, 현진원, 정하숙,
소속 상세정보
 ( Ryu Yea-Seong ) - Jeju National University School of Medicine Department of Biochemistry
현진원 ( Hyun Jin-Won ) - Jeju National University School of Medicine Department of Biochemistry
정하숙 ( Chung Ha-Sook ) - Duksung Women’s University College of Natural Science Department of Food and Nutrition

Abstract


Fucoidan, a natural component of brown seaweed, has various biological activities such as anticancer activity, anti-oxidant, and anti-inflammatory against various cancer cells. However, the fucoidan has been implicated in melanoma cells via apoptosis signaling pathway. Therefore, we investigated apoptosis with fucoidan in A2058 human melanoma cells with dose- and time-dependent manners. In our results, A2058 cells viability decreased at relatively short-time and low-concentration through fucoidan. This effects of fucoidan on A2058 cells appeared to be mediated by the induction of apoptosis, as manifested by morphological changes through DNA-binding dye Hoechst 33342 staining. When a dose of 80 μg/mL fucoidan was treated, the cells were observed: crescent or ring-like structure, chromatin condensation, and nuclear fragmentation. With the increase at 100 μg/mL fucoidan, the cell membrane is intact throughout the total process, including membrane blebbing and loss of membrane integrity as well as increase of sub-G1 DNA. Furthermore, to understand the exact mechanism of fucoidan-treated in A2058 cells, western blotting was performed to detect apoptosis-related protein expression. In this study, Bcl-2 family proteins can be regulated by fucoidan, suggesting that fucoidaninduced apoptosis is modulated by intrinsic pathway. Therefore, expression of Bcl-2 and Bax may result in altered permeability, activating caspase-3 and caspase-9. And the cleaved form of poly ADP-ribose polymerase was detected in fucoidan-treated A2058 cells. These results suggest that A2058 cells are highly sensitive to growth inhibition by fucoidan via apoptosis, as evidenced by activation of extracellular signal-regulated kinases/ p38/Bcl-2 family signaling, as well as alteration in caspase-9 and caspase-3.

키워드

Fucoidan; apoptosis; ROS; MAPKs; A2058; melanoma cells

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