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Inhibition of eIF2α Dephosphorylation Accelerates Pterostilbene-Induced Cell Death in Human Hepatocellular Carcinoma Cells in an ER Stress and Autophagy-Dependent Manner

Inhibition of eIF2α Dephosphorylation Accelerates Pterostilbene-Induced Cell Death in Human Hepatocellular Carcinoma Cells in an ER Stress and Autophagy-Dependent Manner

Chen-Lin Yu, Shun-Fa Yang, Tung-Wei Hung, Chia-Liang Lin, Yi-Hsien Hsieh, Hui-Ling Chiou

Cell Death Dis. 2019 May 28;10(6):418.

PMID: 31138785

Abstract:

Hepatocellular carcinoma (HCC) is the one of the most common cancers worldwide. Because the side effects of current treatments are severe, new effective therapeutic strategies are urgently required. Pterostilbene (PT), a natural analogue of resveratrol, has diverse pharmacologic activities, including antioxidative, anti-inflammatory and antiproliferative activities. Here we demonstrated that PT inhibits HCC cell growth without the induction of apoptosis in an endoplasmic reticulum (ER) stress- and autophagy-dependent manner. Mechanistic studies indicated that the combination of salubrinal and PT modulates ER stress-related autophagy through the phospho-eukaryotic initiation factor 2α/activating transcription factor-4/LC3 pathway, leading to a further inhibition of eIF2α dephosphorylation and the potentiation of cell death. An in vivo xenograft analysis revealed that PT significantly reduced tumour growth in mice with a SK-Hep-1 tumour xenograft. Taken together, our results yield novel insights into the pivotal roles of PT in ER stress- and autophagy-dependent cell death in HCC cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP405060959	Salubrinal		405060-95-9	Price

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