title: Catechin-7-O-xyloside induces apoptosis via endoplasmic reticulum stress and mitochondrial dysfunction in human non-small cell lung carcinoma H1299 cells.
abstract: The medicinal plant Ulmus davidiana var. japonica has significant potential as a cancer chemoprevention agent. Catechin-7-O-xyloside (C7Ox) was purified from ultrafine U. davidiana var. japonica ethanol extract. In the present study, we investigated the apoptotic effect of C7Ox in the non-small cell lung cancer (NSCLC) cell line H1299. C7Ox treatment induced cell death and decreased plasma membrane integrity, an event typical of apoptosis. C7Ox-induced apoptosis was associated with the proteolytic activation of caspase-6, cleavage of poly(ADP-ribose) polymerase (PARP) and loss of mitochondrial membrane potential. C7Ox also induced the endoplasmic reticulum (ER) stress-regulated pro-apoptotic transcription factor CHOP. The suppression of CHOP expression significantly decreased C7Ox-induced cell death, LDH leakage and caspase-6 activation. Antitumor effects, evaluated based on protracted tumor regression, were observed when nude-mice bearing H1299 xenografts were treated with C7Ox. C7Ox-induced tumor regression was accompanied by enhanced expression of CHOP mRNA. Our data suggest that C7Ox can trigger mitochondrial-mediated apoptosis, and that ER stress is critical for C7Ox-induced apoptosis in H1299 NSCLC cells.
authors.affiliation: Department of Food Science and Engineering, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Jang Won
authors.initials: JW
authors.lastname: Yoon
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Lee
authors.forename: Byeong Mo
authors.initials: BM
authors.lastname: Kim
authors.forename: Joungjwa
authors.initials: J
authors.lastname: Ahn
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology*; D053178:Caspase 6 / Q000096:biosynthesis*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008175:Lung Neoplasms / Q000201:enzymology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects*; D009368:Neoplasm Transplantation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D051742:Transcription Factor CHOP / Q000096:biosynthesis / Q000235:genetics; D014994:Xylose / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C497249:DDIT3 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C000591315:catechin-7-O-xyloside; D051742:Transcription Factor CHOP; D002392:Catechin; D014994:Xylose; D007770:L-Lactate Dehydrogenase; D011065:Poly(ADP-ribose) Polymerases; D053178:Caspase 6