Enhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: A paradigm of synergistic molecular targeting treatment for ovarian cancer

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dc.contributor.authorKarabulut B.
dc.contributor.authorKaraca B.
dc.contributor.authorVarol U.
dc.contributor.authorMuslu U.
dc.contributor.authorCakar B.
dc.contributor.authorAtmaca H.
dc.contributor.authorKsm A.
dc.contributor.authorUzunoglu S.
dc.contributor.authorUslu R.
dc.date.accessioned2024-07-22T08:20:43Z
dc.date.available2024-07-22T08:20:43Z
dc.date.issued2010
dc.description.abstractBackground. Ovarian cancer is the most fatal gynecologic malignancies in the world. Although, platinum based treatments are widely used, the disease becomes treatment refractory within two years, and novel treatment options should be searched. All- trans retinoic acid (ATRA) induces growth arrest, differentiation and cell death in some types of cancer cells and its combination with various anticancer agents results in enhanced cytotoxicity. Zoledronic acid is a common bisphosphonate known for its anticancer effects beyond its current use in the treatment of cancer-induced bone disease. We aimed to investigate the possible additive/synergistic effect of both agents in OVCAR-3 and MDAH-2774 ovarian cancer cell lines, since both agents show superiority to conventional cytotoxics in terms of adverse events. Methods. XTT cell proliferation assay was used for showing cytotoxicity. For verifying apoptosis, both DNA Fragmentation by ELISA assay and caspase 3/7 activity measurement were used. OligoGeArray® which consists of 112 apoptosis related genes was used to elucidate the genetic changes within cancer cells. To validate our oligoarray results, quantitative real-time PCR was performed on four selected genes that were maximally effected by the combination treatment: lymphotoxin beta receptor (LTBR), myeloid cell leukemia-1 (MCL-1), tumor necrosis factor receptor superfamily, member 1A (TNFRSF1A), TNFRSF1A-associated death domain protein (TRADD). Results. We demonstrated that a novel combination of ATRA and zoledronic acid is a strong inducer of apoptotic related cell death in both ovarian cancer cells. While the combination therapy significantly induced proapoptotic genes such as tumor necrosis factor receptor superfamily (TNFRSF), TRADD and caspase 4, some of the antiapoptotic genes such as members of MCL-1, LTBR, BAG3 and Bcl-2 family members were inhibited. Conclusions. These are the preliminary molecular results of a novel combination treatment of ATRA and zoledronic acid, with fewer side effects as compared to conventional cytotoxic agents. With additional experimental analysis, it may serve as a good option for the treatment of refractory and elderly ovarian cancer patients, for whom there exists very limited choice of treatment. © 2010 Karabulut et al; licensee BioMed Central Ltd.
dc.identifier.DOI-ID10.1186/1756-9966-29-102
dc.identifier.issn17569966
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/18277
dc.language.isoEnglish
dc.rightsAll Open Access; Gold Open Access; Green Open Access
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectApoptosis
dc.subjectBlotting, Western
dc.subjectCell Proliferation
dc.subjectDiphosphonates
dc.subjectDrug Synergism
dc.subjectFemale
dc.subjectGene Expression Profiling
dc.subjectHumans
dc.subjectImidazoles
dc.subjectOligonucleotide Array Sequence Analysis
dc.subjectOvarian Neoplasms
dc.subjectReverse Transcriptase Polymerase Chain Reaction
dc.subjectRNA, Messenger
dc.subjectTretinoin
dc.subjectTumor Cells, Cultured
dc.subjectTumor Markers, Biological
dc.subjectcaspase 3
dc.subjectcaspase 7
dc.subjectlymphotoxin beta receptor
dc.subjectretinoic acid
dc.subjecttumor necrosis factor receptor 1
dc.subjecttumor necrosis factor receptor associated death domain protein
dc.subjectzoledronic acid
dc.subjectantineoplastic agent
dc.subjectbisphosphonic acid derivative
dc.subjectimidazole derivative
dc.subjectmessenger RNA
dc.subjectretinoic acid
dc.subjecttumor marker
dc.subjectzoledronic acid
dc.subjectapoptosis
dc.subjectarticle
dc.subjectcell proliferation
dc.subjectcell viability
dc.subjectcytotoxicity
dc.subjectdrug effect
dc.subjectenzyme activity
dc.subjecthuman
dc.subjecthuman cell
dc.subjectovary cancer
dc.subjectpriority journal
dc.subjectcell proliferation
dc.subjectDNA microarray
dc.subjectdrug potentiation
dc.subjectfemale
dc.subjectgene expression profiling
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectovary tumor
dc.subjectpathology
dc.subjectreverse transcription polymerase chain reaction
dc.subjecttumor cell culture
dc.subjectWestern blotting
dc.titleEnhancing cytotoxic and apoptotic effect in OVCAR-3 and MDAH-2774 cells with all-trans retinoic acid and zoledronic acid: A paradigm of synergistic molecular targeting treatment for ovarian cancer
dc.typeArticle

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