Resveratrol induced ER expansion and ER caspase-mediated apoptosis in human nasopharyngeal carcinoma cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-03

AUTHORS

Shu-Er Chow, Cheng-Heng Kao, Yi-Tong Albert Liu, Mei-Ling Cheng, Ya-Wen Yang, Yao-Kuan Huang, Chih-Chin Hsu, Jong-Shyan Wang

ABSTRACT

Autophagy and endoplasmic reticulum (ER) stress response is important for cancer cells to maintain malignancy and resistance to therapy. trans-Resveratrol (RSV), a non-flavonoid agent, has been shown to induce apoptosis in human nasopharyngeal carcinoma (NPC) cells. In this study, the involvements of tumor-specific ER stress and autophagy in the RSV-mediated apoptosis were investigated. In addition to traditional autophagosomes, the images of transmission electron microscopy (TEM) indicated that RSV markedly induced larger, crescent-shaped vacuoles with single-layered membranes whose the expanded cisternae contains multi-lamellar membrane structures. Prolonged exposure to RSV induced a massive accumulation of ER expansion. Using an EGFP-LC3B transfection and confocal laser microscopy approach, we found RSV-induced EGFP-LC3 puncta co-localized with ER-tracker red dye, implicating the involvement of LC3II in ER expansion. The proapoptotic effect of RSV was enhanced after suppression of autophagy by ATG7 siRNA or blocking the autophagic flux by bafilomycin A1, but that was not changed after targeted silence of IRE1 or CHOP by siRNA. Using caspase inhibitors, we demonstrated the upregulation of caspase-12 (casp12) and the activation of casp4 were associated with the proapoptotic induction of RSV through the caspase-9/caspase-3 pathway. Intriguingly, siRNA knockdown of casp12, but not caspase-4, decreased the susceptibility of the NPC cells to RSV-mediated apoptosis. Further, we showed that RSV dose-dependently increased the ceramide accumulation as assessed by LC-MS/MS system. Using serine palmitoyltransferase (SPT, a key enzyme of de novo ceramide biosynthesis) inhibitors (L-cycloserine and myriocin), we found the increased ceramide accumulation was strongly correlated with the proapoptotic potential of RSV. This study revealed the ER expansion and upregulation of ER casp12 together may indicate profound biological effects of RSV and contributed to NPC cell death. Targeting the different status of ER stress may provide a possible strategy for cancer treatments. More... »

PAGES

527-541

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10495-013-0945-0

DOI

http://dx.doi.org/10.1007/s10495-013-0945-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016040956

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24264887


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298 Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan
299 rdf:type schema:Organization
300 https://www.grid.ac/institutes/grid.266832.b schema:alternateName University of New Mexico
301 schema:name School of Medicine, University of New Mexico, Albuquerque, NM, USA
302 rdf:type schema:Organization
303 https://www.grid.ac/institutes/grid.454209.e schema:alternateName Keelung Chang Gung Memorial Hospital
304 schema:name Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Keelung, Taiwan
305 rdf:type schema:Organization
 




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