In vitro induction of endoplasmic reticulum stress in human cervical adenocarcinoma HeLa cells by fucoidan.
Int J Biol Macromol. 2019 Jul 8. Epub 2019 Jul 8. PMID: 31295479
Fucoidan is a sulfated hetero-polysaccharide, found in cell-wall composition of brown algae. Recent studies have reported the role of fucoidan in the induction of Endoplasmic Reticulum (ER) stress-related cell death in cancer cells but the mechanism of action of fucoidan in cervical HeLa cells is not well-known. The purpose of this study was to investigate if fucoidan induces HeLa cells death through ER-stress-related cell death and G1 phase arrest. 200-600 μg/ml concentrations of fucoidan inhibited the proliferation of HeLa cells after 48 h of treatment while investigated normal cell lines (HaCaT: Keratinocytes and HEK-293: embryonic kidney) were not affected. The exposure of HeLa cells to these concentrations of fucoidan induced phosphorylationof ER stress sensors followed by upregulation of Bip/GRP78, CHOP expression which triggered a buildup of malfolded proteins in ER, therefore, initiating unfolded protein response (UPR) mechanism. In addition, intracellular calcium levels were elevated following the treatment suggesting that this contributed to the ER stress-induced apoptosis. Fucoidan treatment caused G1phase arrest by inducting CDKIs and inhibiting CDKs and Cyclins as well as apoptosis by activating the mitochondrial-dependent pathway in HeLa cells. We demonstrated that Fucoidan inhibits HeLa cells proliferation by inducingapoptosis, G1 phase arrest, ER stress, and mitochondrial-mediated apoptosis.