5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins
Joint Authors
Lu, Wuguang
Ye, Tingmei
Cai, Xueting
Wang, Xiaoning
Wang, Zhigang
Cao, Peng
Yang, Jie
Hu, Chunping
Zhang, Zhenzhen
Source
Evidence-Based Complementary and Alternative Medicine
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-02-28
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for the treatment of cancer, because it preferentially induces apoptosis in numerous cancer cells with little or no effect on normal cells.
5,7-Dihydroxyflavone is a dietary flavonoid commonly found in many plants.
Here we show that the combined treatment with 5,7-dihydroxyflavone and TRAIL at subtoxic concentrations induced strong apoptotic response in human hepatocarcinoma HepG2 cells, acute leukemia Jurkat T cells, and cervical carcinoma HeLa cells.
We further investigated the mechanisms by which 5,7-dihydroxyflavone augments TRAIL-induced apoptosis in HepG2 cells.
5,7-Dihydroxyflavone up-regulated the expression of pro-apoptotic protein Bax, attenuated the expression of anti-apoptotic proteins Bcl-2, Mcl-1, and IAPs, and reduced the phosphorylation levels of Akt and STAT3, weakening the anti-apoptotic signals thus facilitating the process of apoptosis.
Moreover, 5,7-dihydroxyflavone and TRAIL were well tolerated in mice, and the combination of 5,7-dihydroxyflavone and TRAIL reduced tumor burden in vivo in a HepG2 tumor xenograft model.
Interestingly, 5,7-dihydroxyflavone-mediated sensitization to TRAIL-induced cell death was not observed in normal human hepatocytes L-O2.
These results suggest that the 5,7-dihydroxyflavone in combination with TRAIL might be used for cancer prevention and/or therapy.
American Psychological Association (APA)
Zhang, Zhenzhen& Ye, Tingmei& Cai, Xueting& Yang, Jie& Lu, Wuguang& Hu, Chunping…[et al.]. 2013. 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins. Evidence-Based Complementary and Alternative Medicine،Vol. 2013, no. 2013, pp.1-13.
https://search.emarefa.net/detail/BIM-471959
Modern Language Association (MLA)
Zhang, Zhenzhen…[et al.]. 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins. Evidence-Based Complementary and Alternative Medicine No. 2013 (2013), pp.1-13.
https://search.emarefa.net/detail/BIM-471959
American Medical Association (AMA)
Zhang, Zhenzhen& Ye, Tingmei& Cai, Xueting& Yang, Jie& Lu, Wuguang& Hu, Chunping…[et al.]. 5,7-Dihydroxyflavone Enhances the Apoptosis-Inducing Potential of TRAIL in Human Tumor Cells via Regulation of Apoptosis-Related Proteins. Evidence-Based Complementary and Alternative Medicine. 2013. Vol. 2013, no. 2013, pp.1-13.
https://search.emarefa.net/detail/BIM-471959
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-471959