Search

n-Propyl gallate is a synthetic phenolic antioxidant with potential anti-inflammatory effects. However, the underlying mechanism remains largely unknown. In the present study, we showed that n-propyl gallate increases the expression and activity of the heme oxygenase-1 (HO-1), a stress-inducible protein with potent anti-inflammatory activity, in RAW264.7 macrophages. The inhibition of the HO-1 activity by treatment with zinc (II) protoporphyrin IX (ZnPP) or by knockdown of the HO-1 expression with small interference RNA significantly reversed the inhibitory effect of n-Propyl gallate on activations of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). An additional mechanism study using inhibitors of signaling kinases revealed the involvement of protein kinase Cδ (PKCδ) in the expression of HO-1 induced by n-Propyl gallate. Consistent with these results, n-Propyl gallate increased the intracellular levels of phosphorylated PKCδ in concentration- and time-dependent manners. The inhibitory effects of n-Propyl gallate on LPS-induced iNOS expression and nitric oxide production were also significantly attenuated by pretreatment with the PKCδ inhibitor, rottlerin, or by transfection with PKCδ (K376R), a kinase-inactive form of PKCδ. Taken together, these findings provide the first evidence that n-Propyl gallate exerts its anti-inflammatory effect through PKCδ-mediated up-regulation of HO-1 in macrophages., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 Elsevier B.V. All rights reserved.)