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.