Apoptosis-mediated cytotoxic effects of ibandronic acid on hormone-and drug-refractory prostate cancer cells and human breast cancer cells

Over 80% of patients with advanced breast and prostate cancer ultimately develop bone metastases. Ibandronic acid has proven efficacy for treatment of bone metastasis secondary to breast cancer. This study was designed to investigate the cytotoxic and apoptotic effects of ibandronic acid on hormone- and drug refractory prostate carcinoma DU-145 and human breast cancer MCF-7 cell lines. Cytotoxicity was evaluated using an XTT cell proliferation kit, and apoptosis was assessed by enzyme-linked immuno sorbent assay (histone-DNA fragmentation) and measurement of caspase 3/7 activity. With increasing concentrations of ibandronic acid there was a dose- and time-dependent decrease in cell numbers. MCF-7 cells were more resistant than DU-145 cells (half maximal inhibitory concentrations of 122 and 90 µM, respectively). Ibandronic acid induced apoptosis in both cell lines. The study showed an apoptosis-mediated cytotoxic effect for ibandronic acid (in addition to the already known osteoclast inhibiting effect) in breast cancer patients with bone metastases; which was also observed in prostate cancer cells. Further clinical studies involving breast and prostate cancer patients with bone metastases are warranted to confirm these findings. © 2010 Field House Publishing LLP

Docetaxel and platinum combination chemotherapy in locally advanced or metastatic head and neck cancer

PubMed ID: 18555465Purpose: To assess the efficacy and toxicity of the docetaxel and platinum combination in patients with locoregionally advanced or metastatic squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: A total of 24 patients with metastatic or locoregionally advanced SCCHN treated with docetaxel and platinum combination chemotherapy were retrospectively reviewed. All of them had histologically proven SCCHN, measurable disease and ECOG performance status of 2 or less, and were treated with docetaxel 75 mg/m2 as a 60 min i.v. infusion on day 1, followed by cisplatin 75 mg/m2 or carboplatin AUC 6 as a 60 min i.v. infusion on day 1 every 3 weeks, until disease progression or unacceptable toxicity. Patients were evaluated for response, survival and toxicity. Results: Seven (29%) patients showed partial response (PR) and 1 (4%) complete response (CR) for an overall response rate of 33%. Twelve (50%) patients had stable disease (SD). Disease control rate was 83%. The median follow-up time was 26.4 months (range 2-127), the median time to progresion 16 months (range 2-20), and the median overal survival 19 months (range 2-22). Grade 3-4 hematologic toxicity occurred in 13 (54%) patients. Febrile neutropenia was seen in 5 (21%) patients. Conclusion: Docetaxel plus cisplatin or carboplatin is an effective regimen with acceptable safety profile for palliation of locally advanced or metastatic SCCHN. © 2008 Zerbinis Medical Publications

Overcoming drug resistance in hormone-and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination

PubMed ID: 19288219Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose-and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated C3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers. © Springer Science+Business Media B.V. 2009

Targeting apoptosis in the hormone- and drug-resistant prostate cancer cell line, DU-145, by gossypol/zoledronic acid combination

WOS: 000271517400006PubMed ID: 19716895Possible 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. (C) 2009 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved

Docetaxel/zoledronic acid combination triggers apoptosis synergistically through downregulating antiapoptotic Bcl-2 protein level in hormone-refractory prostate cancer cells

WOS: 000262980300015PubMed ID: 19103299Docetaxel, a semi-synthetic taxane analogue, is used effectively in the treatment of metastatic prostate cancer. Zoledronic acid, the most potent member of bisphosphonates, has shown pleiotropic anti-tumoral effects on prostate cancer cells. We have explored the possible additive/synergistic effects and the apoptotic pathways induced by combination treatment of docetaxel and zoledronic acid in hormone and drug refractory, PC-3 and DU-145 prostate cancer cells. Combination of docetaxel and zoledronic acid synergistically inhibits cell growth in PC-3 and DU-145 cells. Moreover, this effect was due to downregulation of antiapoptotic protein Bcl-2 in PC-3 and DU-145 cells. In conclusion, docetaxel/zoledronic acid combination is potentially a novel and effective approach for the treatment of prostate cancer. (C) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved