Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells.
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 ProfilerTM 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 microM gossypol and 5 microM zoledronic acid resulted in significant down-regulation (>or= 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.
Atmaca
Harika
H
Section of Molecular Biology, Department of Biology, Faculty of Science and Arts, Celal Bayar University, Muradiye, Manisa, Turkey.
Gorumlu
Gurbuz
G
Karaca
Burcak
B
Degirmenci
Mustafa
M
Tunali
Didem
D
Cirak
Yalcin
Y
Purcu
Duygu Unuvar
DU
Uzunoglu
Selim
S
Karabulut
Bulent
B
Sanli
Ulus A
UA
Uslu
Ruchan
R
D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077211:Zoledronic Acid
D043925:Angiogenesis Inducing Agents; D004164:Diphosphonates; D007093:Imidazoles; D012333:RNA, Messenger; D000077211:Zoledronic Acid; D053148:Caspase 3; D053179:Caspase 7; D006072:Gossypol