Gossypol: cotton derivative synergizes with chemo

Rich66 · 10-31-2009, 11:55 PM

J BUON. 2009 Jul-Sep;14(3):479-85.
Enhancement of taxane-induced cytotoxicity and apoptosis by gossypol in human breast cancer cell line MCF-7.

Karaca B, Atmaca H, Uzunoglu S, Karabulut B, Sanli UA, Uslu R.
Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, Bornova, Izmir, Turkey.
Purpose: Gossypol is a natural polyphenolic compound extracted from cotton plant (Gossypium species) which has shown potent inhibitory effect on cell growth of many types of cancers. In this study, we aimed to evaluate the interaction of gossypol with some conventional drugs known to be effective in the treatment of breast cancer, like taxanes, doxorubicin, gemcitabine, cisplatin and vinorelbine, in MCF-7 breast cancer cells. Materials and methods: The XTT viability assay was used to evaluate the cytotoxicity of various cytotoxic agents alone and in combination with gossypol in MCF-7 breast cancer cells. The combination effect analysis of Chou and Talalay was used to identify the most synergistic drug combinations. The possible synergistic effects of the combination of drugs on apoptosis were also evaluated by using two different apoptosis assays. Results: We identified strong synergistic cytotoxic and apoptotic activity of gossypol with taxanes among all other studied cytotoxic drugs. Conclusion: This study provides proof that gossypol combined with taxanes may have potential as a novel future treatment for breast cancer.

PMID: 19810142 [PubMed - in process]

Rich66 · 11-15-2009, 05:03 AM

Eur Cytokine Netw. 2009 Sep;20(3):121-30.
Combined gossypol and zoledronic acid treatment results in synergistic induction of cell death and regulates angiogenic molecules in ovarian cancer cells.

Atmaca H, Gorumlu G, Karaca B, Degirmenci M, Tunali D, Cirak Y, Purcu DU, Uzunoglu S, Karabulut B, Sanli UA, Uslu R.
Section of Molecular Biology, Department of Biology, Faculty of Science and Arts, Celal Bayar University, Muradiye, Manisa, Turkey, Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, Bornova, Izmir, Turkey.
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 muM gossypol and 5 muM 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.

PMID: 19825521 [PubMed - in process]

Cell Biol Int. 2009 Nov;33(11):1165-72. Epub 2009 Aug 28.
Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination.

Sanli UA, Gorumlu G, Erten C, Gul MK, Cengiz E, Kucukzeybek Y, Karaca B, Atmaca H, Uzunoglu S, Karabulut B, Uslu R.
Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, 35100 Bornova, Izmir, Turkey.
Possible synergistic cytotoxic and apoptotic effects of gossypol with zoledronic acid on DU-145 cells were explored, along with the rationale behind any observed synergism due to the different apoptotic proteins involved. XTT cell proliferation assay was used to assess the cytotoxicity, and DNA fragmentation and caspase 3/7 activity were measured to verify apoptosis. Human Apoptosis Array was used to evaluate apoptotic proteins. The synergistic cytotoxic combination treatment had a versatile effect on apoptotic proteins, through inhibition of anti-apoptotic proteins (including cIAP-1, cIAP-2, survivin, livin, claspin, p53, p21, PON-2 and heat shock proteins) and concurrently the induction of pro-apoptotic proteins (Bad, Bax, Fas, FADD, cleaved caspase-3 and p27). Both drugs had a minimal toxicity profile comparing to cytotoxic agents. Combination treatments targeting many pivotal apoptosis-related proteins may be a rationale option for treatment of prostate cancer.

PMID: 19716895 [PubMed - in process]