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Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells.
Breast Cancer Res Treat. 2010 Nov; 124(2):349-60.BC

Abstract

Studies were performed to determine the influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to adriamycin (doxorubicin) in four human breast tumor cell lines and one murine breast tumor line. Sildenafil did not interfere with the effectiveness of adriamycin in any of the cell lines tested. Sildenafil also failed to protect MDA-MB231 cells against the cytotoxicity of cisplatin, taxol or camptothecin. Sildenafil enhanced sensitivity to adriamycin markedly in the p53 mutant MDA-MB231 and p53 null MCF-7/E6 cells and moderately in the MCF-7/caspase 3 and 4T1 cell lines. In the MDA-MB231 cells, sildenafil increased the extent of DNA damage induced by adriamycin as well as the extent of apoptotic cell death. Sildenafil did not influence sensitivity to adriamycin in bone marrow cells or macrophages. In an immunocompetent model of breast cancer (4T1 mammary carcinoma in Balb/c mice), sildenafil did not attenuate the antitumor effects of adriamycin; furthermore, the combination of sildenafil with adriamycin was no more toxic to the animals than adriamycin alone. Given that sildenafil has been shown to have the potential to protect the heart against the toxicity of adriamycin, these studies suggest that the inclusion of sildenafil with conventional chemotherapeutic protocols involving adriamycin (and possibly cisplatin, camptothecin and/or paclitaxel) should not compromise the antitumor effectiveness of these drugs nor enhance their toxicity to the patient.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Massey Cancer Center, 401 College St., Richmond, VA 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

20155316

Citation

Di, Xu, et al. "Influence of the Phosphodiesterase-5 Inhibitor, Sildenafil, On Sensitivity to Chemotherapy in Breast Tumor Cells." Breast Cancer Research and Treatment, vol. 124, no. 2, 2010, pp. 349-60.
Di X, Gennings C, Bear HD, et al. Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells. Breast Cancer Res Treat. 2010;124(2):349-60.
Di, X., Gennings, C., Bear, H. D., Graham, L. J., Sheth, C. M., White, K. L., & Gewirtz, D. A. (2010). Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells. Breast Cancer Research and Treatment, 124(2), 349-60. https://doi.org/10.1007/s10549-010-0765-7
Di X, et al. Influence of the Phosphodiesterase-5 Inhibitor, Sildenafil, On Sensitivity to Chemotherapy in Breast Tumor Cells. Breast Cancer Res Treat. 2010;124(2):349-60. PubMed PMID: 20155316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to chemotherapy in breast tumor cells. AU - Di,Xu, AU - Gennings,Chris, AU - Bear,Harry D, AU - Graham,Laura J, AU - Sheth,Christopher M, AU - White,Kimber L,Jr AU - Gewirtz,David A, Y1 - 2010/02/13/ PY - 2009/12/02/received PY - 2010/01/20/accepted PY - 2010/2/16/entrez PY - 2010/2/16/pubmed PY - 2011/2/10/medline SP - 349 EP - 60 JF - Breast cancer research and treatment JO - Breast Cancer Res Treat VL - 124 IS - 2 N2 - Studies were performed to determine the influence of the phosphodiesterase-5 inhibitor, sildenafil, on sensitivity to adriamycin (doxorubicin) in four human breast tumor cell lines and one murine breast tumor line. Sildenafil did not interfere with the effectiveness of adriamycin in any of the cell lines tested. Sildenafil also failed to protect MDA-MB231 cells against the cytotoxicity of cisplatin, taxol or camptothecin. Sildenafil enhanced sensitivity to adriamycin markedly in the p53 mutant MDA-MB231 and p53 null MCF-7/E6 cells and moderately in the MCF-7/caspase 3 and 4T1 cell lines. In the MDA-MB231 cells, sildenafil increased the extent of DNA damage induced by adriamycin as well as the extent of apoptotic cell death. Sildenafil did not influence sensitivity to adriamycin in bone marrow cells or macrophages. In an immunocompetent model of breast cancer (4T1 mammary carcinoma in Balb/c mice), sildenafil did not attenuate the antitumor effects of adriamycin; furthermore, the combination of sildenafil with adriamycin was no more toxic to the animals than adriamycin alone. Given that sildenafil has been shown to have the potential to protect the heart against the toxicity of adriamycin, these studies suggest that the inclusion of sildenafil with conventional chemotherapeutic protocols involving adriamycin (and possibly cisplatin, camptothecin and/or paclitaxel) should not compromise the antitumor effectiveness of these drugs nor enhance their toxicity to the patient. SN - 1573-7217 UR - https://www.unboundmedicine.com/medline/citation/20155316/Influence_of_the_phosphodiesterase_5_inhibitor_sildenafil_on_sensitivity_to_chemotherapy_in_breast_tumor_cells_ L2 - https://doi.org/10.1007/s10549-010-0765-7 DB - PRIME DP - Unbound Medicine ER -