title: Propyl gallate sensitizes human lung cancer cells to cisplatin-induced apoptosis by targeting heme oxygenase-1 for TRC8-mediated degradation.
abstract: 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.
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Jo
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea.
authors.forename: Seong Ji
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea. Electronic address: bckim@kangwon.ac.kr.
authors.forename: Byung-Chul
authors.initials: BC
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011435:Propyl Gallate / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C114025:RNF139 protein, human; D011956:Receptors, Cell Surface; D025801:Ubiquitin; D011435:Propyl Gallate; D045304:Cytochromes c; D051547:Heme Oxygenase-1; D046988:Proteasome Endopeptidase Complex; D002945:Cisplatin
keywords: Drug sensitivity; HO-1 degradation; Lung cancer; Propyl gallate; TRC8 E3 ligase