Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells

 

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dc.contributor.author Hiss, Donavon en_ZA
dc.contributor.author Gabriels, Gary en_ZA
dc.contributor.author Folb, Peter en_ZA
dc.date.accessioned 2015-10-12T11:00:06Z
dc.date.available 2015-10-12T11:00:06Z
dc.date.issued 2007 en_ZA
dc.identifier.citation Hiss, D. C., Gabriels, G. A., & Folb, P. I. (2007). Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells. Cancer Cell Int, 7(5), 1-14. en_ZA
dc.identifier.uri http://hdl.handle.net/11427/14206
dc.identifier.uri http://dx.doi.org/10.1186/1475-2867-7-5
dc.description.abstract BACKGROUND:The pharmacologic modulatory effects of the antibiotic, tunicamycin (TM), on multidrug-resistant human UWOV2 ovarian cancer cells are reported. The UWOV2 cell line was derived from a cystadenocarcinoma in a patient refractory to combination chemotherapy with actinomycin D, vincristine (VCR), cis-diaminedichloroplatinum (II) (CDDP) and doxorubicin (DXR). In an attempt to explain drug resistance in this cell line, we examined the effects of TM on their sensitivity to various anticancer drugs, the uptake, efflux and retention of [3H]VCR, and their ability to bind [14C]DXR and [3H]azidopine (AZD), a photoaffinity label of the multidrug transporter, P-glycoprotein (Pgp). RESULTS: TM effectively decreased the EC50 for DXR, EXR, VCR and CDDP, thus enhancing their cytotoxicity. The antibiotic also prolonged the intracellular retention time of [3H]VCR and increased the binding of both [14C]DXR and [3H]AZD to the cells. CONCLUSION: It is concluded that the pharmacomodulatory effects of TM in these cells are mediated by global inhibition of protein and glycoprotein synthesis and synergistic interaction with antineoplastic drugs. The ability of TM to enhance the sensitivity of drug resistant tumour cells may have impact on the design and optimization of novel resistance modifiers to improve the efficacy of combination treatment of intractable neoplasms. en_ZA
dc.language.iso eng en_ZA
dc.publisher BioMed Central Ltd en_ZA
dc.rights This is an Open Access article distributed under the terms of the Creative Commons Attribution License en_ZA
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_ZA
dc.source Cancer Cell International en_ZA
dc.source.uri http://www.cancerci.com/ en_ZA
dc.title Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells en_ZA
dc.type Journal Article en_ZA
uct.type.publication Research en_ZA
uct.type.resource Article en_ZA
dc.publisher.institution University of Cape Town
dc.publisher.faculty Faculty of Health Sciences en_ZA
dc.publisher.department Division of Clinical Pharmacology en_ZA
uct.type.filetype Text
uct.type.filetype Image
dc.identifier.apacitation Hiss, D., Gabriels, G., & Folb, P. (2007). Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells. <i>Cancer Cell International</i>, http://hdl.handle.net/11427/14206 en_ZA
dc.identifier.chicagocitation Hiss, Donavon, Gary Gabriels, and Peter Folb "Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells." <i>Cancer Cell International</i> (2007) http://hdl.handle.net/11427/14206 en_ZA
dc.identifier.vancouvercitation Hiss D, Gabriels G, Folb P. Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells. Cancer Cell International. 2007; http://hdl.handle.net/11427/14206. en_ZA
dc.identifier.ris TY - Journal Article AU - Hiss, Donavon AU - Gabriels, Gary AU - Folb, Peter AB - BACKGROUND:The pharmacologic modulatory effects of the antibiotic, tunicamycin (TM), on multidrug-resistant human UWOV2 ovarian cancer cells are reported. The UWOV2 cell line was derived from a cystadenocarcinoma in a patient refractory to combination chemotherapy with actinomycin D, vincristine (VCR), cis-diaminedichloroplatinum (II) (CDDP) and doxorubicin (DXR). In an attempt to explain drug resistance in this cell line, we examined the effects of TM on their sensitivity to various anticancer drugs, the uptake, efflux and retention of [3H]VCR, and their ability to bind [14C]DXR and [3H]azidopine (AZD), a photoaffinity label of the multidrug transporter, P-glycoprotein (Pgp). RESULTS: TM effectively decreased the EC50 for DXR, EXR, VCR and CDDP, thus enhancing their cytotoxicity. The antibiotic also prolonged the intracellular retention time of [3H]VCR and increased the binding of both [14C]DXR and [3H]AZD to the cells. CONCLUSION: It is concluded that the pharmacomodulatory effects of TM in these cells are mediated by global inhibition of protein and glycoprotein synthesis and synergistic interaction with antineoplastic drugs. The ability of TM to enhance the sensitivity of drug resistant tumour cells may have impact on the design and optimization of novel resistance modifiers to improve the efficacy of combination treatment of intractable neoplasms. DA - 2007 DB - OpenUCT DO - 10.1186/1475-2867-7-5 DP - University of Cape Town J1 - Cancer Cell International LK - https://open.uct.ac.za PB - University of Cape Town PY - 2007 T1 - Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells TI - Combination of tunicamycin with anticancer drugs synergistically enhances their toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells UR - http://hdl.handle.net/11427/14206 ER - en_ZA


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