Open Access

ARTICLE

Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells

Harika Atmaca¹, Gurbuz Gorumlu², Burcak Karaca², Mustafa Degirmenci², Didem Tunali², Yalcin Cirak², Duygu Unuvar Purcu¹, Selim Uzunoglu¹, Bulent Karabulut², Ulus A. Sanli², Ruchan Uslu²

1 Section of Molecular Biology, Department of Biology, Faculty of Science and Arts, Celal Bayar University, Muradiye, Manisa, Turkey
2 Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, Bornova, Izmir, Turkey

* Corresponding Author: R. Uslu M.D.,

European Cytokine Network 2009, 20(3), 121-130. https://doi.org/10.1684/ecn.2009.0159

Accepted 28 July 2009;

Abstract

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^TM 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 apopto-sis. This effect was observed to happen in a dose- and time-dependent manner. Moreover, the combination treat-ment 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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