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

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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.accessioned2024-07-22T08:19:15Z
dc.date.available2024-07-22T08:19:15Z
dc.date.issued2012
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.
dc.identifier.DOI-ID10.1007/s00432-012-1187-1
dc.identifier.issn14321335
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/17572
dc.language.isoEnglish
dc.subjectAntineoplastic Agents, Phytogenic
dc.subjectApoptosis
dc.subjectBreast Neoplasms
dc.subjectCell Line, Tumor
dc.subjectFemale
dc.subjectGossypol
dc.subjectHumans
dc.subjectMitochondria
dc.subjectReceptors, TNF-Related Apoptosis-Inducing Ligand
dc.subjectTNF-Related Apoptosis-Inducing Ligand
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectclusterin
dc.subjectcytochrome c
dc.subjectdeath receptor 4
dc.subjectdeath receptor 5
dc.subjectFas antigen
dc.subjectFas associated death domain protein
dc.subjectisosorbide
dc.subjectprotein
dc.subjectprotein BAD
dc.subjectprotein Bax
dc.subjectprotein bcl 2
dc.subjectprotein bcl x
dc.subjectprotein Bid
dc.subjectprotein cIAP
dc.subjectsecond mitochondrial activator of caspase
dc.subjecttumor necrosis factor related apoptosis inducing ligand
dc.subjectunclassified drug
dc.subjectX linked inhibitor of apoptosis
dc.subjectapoptosis
dc.subjectarticle
dc.subjectbreast cancer
dc.subjectcancer cell culture
dc.subjectcancer combination chemotherapy
dc.subjectcell viability
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectDNA fragmentation
dc.subjectdose response
dc.subjectdrug cytotoxicity
dc.subjectdrug dose sequence
dc.subjectdrug effect
dc.subjectdrug potentiation
dc.subjectenzyme activity
dc.subjectenzyme linked immunosorbent assay
dc.subjecthuman
dc.subjecthuman cell
dc.subjectIC 50
dc.subjectmonotherapy
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectWestern blotting
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 levels
dc.typeArticle

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