TRAIL-Induced Apoptosis in TRAIL-Resistant Breast Carcinoma Through Quercetin Cotreatment

Breast cancer is the most commonly diagnosed cancer in women. There is a continued interest for the development of more efficacious treatment regimens for breast carcinoma. Recombinant human tumor necrosis factor–related apoptosis-inducing ligand (rhTRAIL) shows potential as a potent anticancer ther...

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Bibliographic Details
Published in:Breast cancer : basic and clinical research 2018-01, Vol.2018 (12), p.1178223417749855-1178223417749855
Main Authors: Manouchehri, Jasmine M, Turner, Katherine A, Kalafatis, Michael
Format: Article
Language:English
Subjects:
Amino acids
Apoptosis
Authorship
Breast cancer
Clinical trials
Cytotoxicity
Ligands
Molecular weight
Original Research
Prostate cancer
Protein expression
Proteins
Software
Tumor necrosis factor-TNF
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Summary:Breast cancer is the most commonly diagnosed cancer in women. There is a continued interest for the development of more efficacious treatment regimens for breast carcinoma. Recombinant human tumor necrosis factor–related apoptosis-inducing ligand (rhTRAIL) shows potential as a potent anticancer therapeutic for the treatment of breast cancer, whereas displaying minimal toxicity to normal cells. However, the promise of rhTRAIL for the treatment of breast cancer is dismissed by the resistance to rhTRAIL-induced apoptosis exhibited by many breast cancers. Thus, a cotreatment strategy was examined by applying the natural compound quercetin (Q) as a sensitizing agent for rhTRAIL-resistant breast cancer BT-20 and MCF-7 cells. Quercetin was able to sensitize rhTRAIL-resistant breast cancers to rhTRAIL-induced apoptosis as detected by Western blotting through the proteasome-mediated degradation of c-FLIPL and through the upregulation of DR5 expression transcriptionally. Overall, these in vitro findings establish that Q is an effective sensitizing agent for rhTRAIL-resistant breast cancers.
ISSN:1178-2234
1178-2234
DOI:10.1177/1178223417749855