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

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...

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Bibliographic Details
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
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2016.06.052