SHUN-FA YANGTUNG-WEI HUNGCHIA-LIANG LINYI-HSIEN HSIEHHUI-LING CHIOU2026-10-162026-10-162019-06-01Pure ID: 15392597Pure UUID: 2d41b76f-7825-436b-af9a-0195da53e78d10.1038/s41419-019-1639-5https://www.scopus.com/pages/publications/85066312098https://scholars.csmu.edu.tw/handle/123456789/25554Hepatocellular 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.enjournal article