Propyl gallate sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting heme oxygenase-1 for TRC8-mediated degradation

• Published in: European journal of pharmacology 2016-10, Vol.788, p.321-327
• Main Authors: Jo, Eun Ji, Park, Seong Ji, Kim, Byung-Chul
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Line, Tumor; Cisplatin - pharmacology; Cytochromes c - secretion; Down-Regulation - drug effects; Drug sensitivity; Drug Synergism; Heme Oxygenase-1 - metabolism; HO-1 degradation; Humans; Lung cancer; Lung Neoplasms - pathology; Mitochondria - drug effects; Mitochondria - metabolism; Propyl gallate; Propyl Gallate - pharmacology; Proteasome Endopeptidase Complex - metabolism; Proteolysis - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; Receptors, Cell Surface - metabolism; TRC8 E3 ligase; Ubiquitin - metabolism
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2016.06.052

Heme oxygenase-1 (HO-1) significantly contributes to survival of cancer cells and is being considered as one of therapeutic targets for cancer treatment. Propyl gallate (PG) is a synthetic phenolic compound that possess a potent anti-oxidant and anti-inflammatory activities. In the present study, we investigated whether PG exhibit an anti-cancer effect through modulating HO-1 activation. In human non-small cell lung cancer (NSCLC) cells, treatment with PG dose-dependently diminished HO-1 protein levels without changing its mRNA levels and consequently decreased HO-1 activity. PG also significantly enhanced the sensitivity of NSCLC cells to cisplatin-induced apoptosis, and this effect was attenuated by overexpression of HO-1. Mechanistically, PG exerted its chemosensitization effect by down-regulating HO-1 protein expression through a TRC8 (translocation in renal carcinoma, chromosome 8)-mediated ubiquitin-proteasome pathway. Collectively, our data provide the potential application of PG in combination chemotherapy to enhance drug sensitivity in lung cancer by targeting HO-1.