Pretreatment with AT-101 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing death receptors 4 and 5 protein levels

Basit Öğe Kaydı
dc.contributor.authorKisim A.
dc.contributor.authorAtmaca H.
dc.contributor.authorCakar B.
dc.contributor.authorKarabulut B.
dc.contributor.authorSezgin C.
dc.contributor.authorUzunoglu S.
dc.contributor.authorUslu R.
dc.contributor.authorKaraca B.
dc.date.accessioned2019-10-26T21:47:25Z
dc.date.available2019-10-26T21:47:25Z
dc.date.issued2012
dc.departmentEge Üniversitesien_US
dc.description.abstractPurpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily and has been shown to induce extrinsic pathway of apoptosis in many types of cancer cells. AT-101, an (-)-enantiomer of gossypol, is a potent anticancer agent that is shown to be an inhibitor of Bcl-2/Bcl-XL. In this study, we searched whether pretreatment with either of these drugs would result in the enhancement of apoptosis through induction of death receptors and activation of mitochondrial pathways within breast cancer cells. Methods: Human breast cancer (MCF-7 and MDA-MB-231) and normal breast cells (MCF-10A) were treated with drugs alone/in combination/sequentially. XTT cell viability assay was used to evaluate cytotoxicity. For showing apoptosis, both DNA Fragmentation and caspase 3/7 activity measurements were done. ELISA and Western blot analysis were done to assess DR4 and DR5 protein levels. The expression levels of apoptotic proteins were assessed by human apoptosis antibody array. Results: The sequential treatment of AT-101 followed by TRAIL resulted in significant synergistic cytotoxicity and apoptosis. Moreover, pretreatment of breast cancer cells with AT-101 and then with TRAIL caused enhancement of the expression levels of DR4 and DR5 in both cancer cell lines, suggesting that these cells were under strong apoptotic stimuli. Conclusions: These findings all together, strongly suggest that pretreatment with AT-101 enhances TRAIL-induced death-inducing signaling complex resulting in the engagement of the mitochondrial pathway to apoptosis in breast cancer cells. These promising, preliminary results make AT-101 and TRAIL a novel combination treatment candidate for breast cancer. © Springer-Verlag 2012.en_US
dc.description.sponsorshipCelal Bayar Üniversitesien_US
dc.description.sponsorshipAcknowledgments This work was supported by grants from Celal Bayar University Scientific Research Projects Committee of Celal Bayar University. (Project No: FBE 2009-093). --en_US
dc.identifier.doi10.1007/s00432-012-1187-1en_US
dc.identifier.endpage1163en_US
dc.identifier.issn0171-5216
dc.identifier.issue7en_US
dc.identifier.pmid22411600en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage1155en_US
dc.identifier.urihttps://doi.org/10.1007/s00432-012-1187-1
dc.identifier.urihttps://hdl.handle.net/11454/18607
dc.identifier.volume138en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.relation.ispartofJournal of Cancer Research and Clinical Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApoptosisen_US
dc.subjectAT-101en_US
dc.subjectMCF-7en_US
dc.subjectMDA-MB-231en_US
dc.subjectSensitizationen_US
dc.subjectTRAILen_US
dc.titlePretreatment with AT-101 enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of breast cancer cells by inducing death receptors 4 and 5 protein levelsen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

Scopus İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu