Browsing by Author "Purcu D.U."

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    Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells
    (2009) Atmaca H.; Gorumlu G.; Karaca B.; Degirmenci M.; Tunali D.; Cirak Y.; Purcu D.U.; Uzunoglu S.; Karabulut B.; Sanli U.A.; Uslu R.
    In the present study, we aimed to evaluate the possible synergistic, cytotoxic effects of combination treatment of gossypol and zoledronic acid, in human ovarian cancer cell lines, OVCAR-3 and MDAH-2774, and to elucidate the role of this novel combination treatment on angiogenesis-related molecules in ovarian cancer. The XTT cell viability assay was used for showing cytotoxicity. Both DNA fragmentation by ELISA assay and caspase 3/7 activity measurement were used for demonstrating apoptosis. To elucidate the angiogenic molecules affected by combination treatment, mRNA levels of angiogenic molecules were measured using the Human Angiogenesis RT2 Profiler™ PCR Array (SuperArray, Frederick, MD) in ovarian cancer cell lines, OVCAR-3 and MDAH-2774.The combined treatment resulted in significant, synergistic cytotoxicity, and induced apoptosis. This effect was observed to happen in a dose- and time-dependent manner. Moreover, the combination treatment of 10 μM gossypol and 5 μM zoledronic acid resulted in significant down-regulation (≥ thee-fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3 and MDAH-2774 cells as compared to the untreated control. However, this effect was different in the two ovarian cancer cell lines observed. Gossypol, in combination with zoledronic acid, may provide a rational treatment option for ovarian cancer, not only by direct inhibition of cell proliferation, but also inhibition of angiogenesis-related molecules.
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    The effect of racemic gossypol and AT-101 on angiogenic profile of OVCAR-3 cells: A preliminary molecular framework for gossypol enantiomers
    (2009) Varol U.; Karaca B.; Tunali D.; Degirmenci M.; Cirak Y.; Purcu D.U.; Uzunoglu S.; Sezgin C.; Karabulut B.; Sanli U.A.; Uslu R.
    Aim: To compare the effect of racemic gossypol with its (-)/(-) enantiomer (AT-101) on expression profiles of angiogenic molecules by mRNA levels in human ovarian cancer cell line OVCAR-3. Methods: Cell viability assay (2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium hydroxide) was used to detect cytotoxicity of gossypol enantiomers. DNA fragmentation by an enzyme-linked immunosorbent (ELISA) assay was used to evaluate the rate of apoptosis. The mRNA expression levels of angiogenic molecules were investigated by Human Angiogenesis RT2 Profiler™ PCR Array (SuperArray, Frederick, MD). Results: Both racemic form and AT-101 resulted in a significant cytotoxicity and induced apoptosis. This effect was observed in a dose- and time dependent manner. However, AT-101 was much more potent. In addition, the treatment of 10 μM of racemic gossypol alone and 3 μM of AT-101 alone resulted in significant down-regulation (≥ 3 fold) in mRNA levels of some pivotal angiogenic molecules in OVCAR-3, but altered gene profiles were different by the treatment of each enantiomer. Conclusion: The efficacy of two gossypol enantiomers in OVCAR-3 cells showed distinction. AT-101 was much more potent than racemic gossypol, not only by means of cell death and apoptosis, but also by modulation of angiogenic molecules released from OVCAR-3 cells. Further studies with endothelial cells should be done to verify the anti-angiogenic effect of gossypol enantiomers in cancer treatment.
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    High-resolution melting analysis for screening of Turkish germline mutations in BRCA1 and BRCA2; [Türk hasta popülasyonunda BRCA1 ve BRCA2 germline mutasyonlarïnïn high resolution melting analizi ile taranması]
    (UHOD - Uluslararasi Hematoloji Onkoloji Dergisi, 2010) Purcu D.U.; Karaca B.; Kapkac M.; Ozdemir N.; Uzunoglu S.; Uslu R.
    The germline mutations of breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the two most frequently mutated genes in inherited breast and ovarian cancer. Among the most known mutations in these tumor suppressor genes are 5382insC and 185delAG in BRCA1 and 6174delT in BRCA2. The aim of the current study was to investigate the frequency of these BRCA1 and BRCA2 mutations in Western Turkish population. Twenty-five women with a history of self breast cancer and family history, 25 women with a familial history of breast cancer in their first degree-relatives and five healthy women formed the studied groups. DNA from peripheral blood was extracted and analyzed by high-resolution melting (HRM) analysis. None of the 50 patients and five healthy individuals was found to carry 185delAG mutation in BRCA1 and the 6174delT mutation in BRCA2. But, we found the 5382insC mutation in exon 20 of BRCA1 in five patients, having a strong family history. Four of these five patients were from the same family. Our preliminary results indicate that penetrance of 5382insC mutation in BRCA1 mutations is dominant in Turkish population; however, it seems there might be some other genes that contribute more significantly to familial breast carcinoma in Turkish population in BRCA.