Chrysin overcomes TRAIL resistance of cancer cells through Mcl-1 downregulation by inhibiting STAT3 phosphorylation

Source: Lirdprapamongkol K et al Int J Oncol. 2013 May 1. doi: 10.3892/ijo.2013.1926.
Organisation: Laboratory of Biochemistry, Chulabhorn Research Institute, Bangkok 10210, Thailand.

myeloid cell leukemia sequence.. signal transducer and activato.. dna binding protein

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various types of cancer cells without harming normal cells, but TRAIL resistance has been frequently observed in cancer cells. Propolis (bee glue) is a material collected from various plants by honeybees and is a rich source of bioactive compounds, including the natural flavonoid chrysin, which possesses multiple anticancer effects. We investigated the mechanism underlying the TRAIL sensitization effect of chrysin, which is a major constituent of Thai propolis, in human lung and cervical cancer cell lines. Propolis extract and chrysin sensitizes A549 and HeLa human cancer cell lines to TRAIL-induced apoptosis. The TRAIL sensitization effect of chrysin is not mediated by inhibition of TRAIL-induced NF-kappaB activation or by glutathione depletion. Immunoblot analysis using a panel of anti-apoptotic proteins revealed that chrysin selectively decreases the levels of Mcl-1 protein, by downregulating Mcl-1 gene expression as determined by qRT-PCR. The contribution of Mcl-1 in TRAIL resistance was confirmed by si-Mcl-1 knockdown. Among signaling pathways that regulate Mcl-1 gene expression, only constitutive STAT3 phosphorylation was suppressed by chrysin. The proposed action of chrysin in TRAIL sensitization by inhibiting STAT3 and downregulating Mcl-1 was supported by using a STAT3specific inhibitor, cucurbitacin-I, which decreased Mcl-1 levels and enhanced TRAIL-induced cell death, similar to that observed with chrysin treatment. In conclusion, we show the potential of chrysin in overcoming TRAIL resistance of cancer cells and elucidate its mechanism of action
MHDA- 2013/05/03 06:00    Medline  Literature Alert  Gene-Gene Link  Gene-Disease Link  
Relevant Pathways

This article mentions proteins present in the following molecular pathways (click to explore):

 IL‑4 Signaling Pathway
 Signaling Events Mediated By T..
 ERK1/ERK2 Mapk Signaling Pathw..
 Micrornas In Cardiomyocyte Hyp..
 IL‑9 Signaling Pathway
 E2f Transcription Factor Netwo..
 ERBB2/ERBB3 Signaling Events
 Prolactin Signaling Pathway
 IL 6 Signaling Pathway
 IL‑6 Signaling Pathway
 IL‑7 Signaling Pathway
 IL2‑Mediated Signaling Events
 Role Of ERBB2 In Signal Transd..
 IL12 Signaling Mediated By STA..
 Tgf Beta Signaling Pathway
 Serotonin RECEPTOR 2 And STAT3..
 IL12‑Mediated Signaling Events
 IL12 Signaling Pathway
 Egf Signaling Pathway
 Androgen Receptor Signaling Pa..
 Physiological And Pathological..
 Leptin Signaling Pathway
 IFN‑Gamma Pathway
 IL‑5 Signaling Pathway
 PDGFR‑Beta Signaling Pathway
 NOTCH‑Mediated Hes/Hey Network
 IL17 Signaling Pathway
 Signaling Events Mediated By P..
 IL‑3 Signaling Pathway
 Tfs Regulate Mirnas Related To..
 Type III Interferon Signaling
 Interferon Type I
 Neurotrophic FACTOR‑Mediated T..
 Notch Signaling Pathway
 Signaling Of Hepatocyte Growth..
 Tpo Signaling Pathway
 HIF‑1‑Alpha Transcription Fact..
 IL23‑Mediated Signaling Events
 IL‑2 Signaling Pathway
 Egf Receptor (ERBB1) Signaling..
 IL6‑Mediated Signaling Events
 STAT3 Signaling Pathway
 Pdgf Signaling Pathway
 EGF‑Egfr Signaling Pathway
 IL27‑Mediated Signaling Events
 Kit Receptor Signaling Pathway
 Signaling Events Mediated By H..
 Signaling Events Mediated By S..
 ERBB1 Downstream Signaling
 Epo Receptor Signaling
 Tsh Signaling Pathway
 Direct P53 Effectors
 RAC1 Signaling Pathway

Other Topics Mentioned:

Uterine Cervical Neoplasms tnf superfamily nf‑kappa‑b

   abstracted provided by MEDLINE/PubMed, a database of the U.S. National Library of Medicine.

Article Toolkit

More Stories Like This. Click to see other articles in this area.
Read article in Utopia Documents, the revolutionary new way to read scientific papers that integrates directly with SciBite
Extract Chemical Structures, Via the Chemicalize from ChemAxon service*.
Report An Error. If you think this article is incorrectly tagged or missing something let us know!

* Denotes third party service. SciBite is not responsible for any third party service.

Altmetric Ranking

Altmetric tracks article mentions across social media. This articles Altmetric score is:

Location Info

Not Available

Related Products


Sponsored Links