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

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Issued Date

2013

Resource Type

Article

File Type

application/pdf

ISSN

10196439

DOI

10.3892/ijo.2013.1926

Other identifier(s)

2-s2.0-84879460546

Rights Holder(s)

มหาวิทยาลัยศรีนครินทรวิโรฒ

Bibliographic Citation

International Journal of Oncology. Vol 43, No.1 (2013), p.329-337

Suggested Citation

Lirdprapamongkol K., Sakurai H., Abdelhamed S., Yokoyama S., Athikomkulchai S., Viriyaroj A., Awale S., Ruchirawat S., Svasti J., Saiki I. Chrysin overcomes TRAIL resistance of cancer cells through Mcl-1 downregulation by inhibiting STAT3 phosphorylation. International Journal of Oncology. Vol 43, No.1 (2013), p.329-337. doi:10.3892/ijo.2013.1926 Retrieved from: https://hdl.handle.net/20.500.14740/6630

Title

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

Author(s)

Lirdprapamongkol K.
 Sakurai H.
 Abdelhamed S.
 Yokoyama S.
 Athikomkulchai S.
 Viriyaroj A.
 Awale S.
 Ruchirawat S.
 Svasti J.
 Saiki I.

Abstract

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-κB 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 STAT3-specific inhibitor, cucurbitacin-I, which decreased Mcl-1 levels and enhanced Key words: tumor necrosis factor-related apoptosis-inducing ligand, STAT3, apoptosis, propolis, natural products 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.

Subject(s)

Chrysin
 Cucurbitacin
 Glutathione
 Propolis
 Protein mcl 1
 STAT3 protein
 Tumor necrosis factor related apoptosis inducing ligand
 Analysis
 Antineoplastic activity
 Apoptosis
 Article
 Cancer cell
 Cancer cell culture
 Cancer resistance
 Controlled study
 Down regulation
 Enzyme activation
 Enzyme inhibition
 Female
 Gene expression
 HeLa cell
 Honeybee
 Human
 Human cell
 Immunoblotting
 Priority journal
 Protein phosphorylation
 Reverse transcription polymerase chain reaction
 Sensitization
 Signal transduction
 Uterine cervix cancer
 Female
 Flavonoids
 Gene Expression Regulation, Neoplastic
 Glutathione
 HeLa Cells
 Humans
 Lung Neoplasms
 Myeloid Cell Leukemia Sequence 1 Protein
 NF-kappa B
 Phosphorylation
 Propolis
 STAT3 Transcription Factor
 TNF-Related Apoptosis-Inducing Ligand
 Uterine Cervical Neoplasms

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URI

https://hdl.handle.net/20.500.14740/6630

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Scopus: Year 1983-2021

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