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Ishiguro K, Zhu YL, Lin ZP, et al. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines. J Transl Sci. 2016;2(2):117-124doi: 10.15761/JTS.1000127.
Ishiguro, K., Zhu, Y. L., Lin, Z. P., Penketh, P. G., Shyam, K., Zhu, R., Baumann, R. P., Sartorelli, A. C., Rutherford, T. J., & Ratner, E. S. (2016). Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines. Journal of translational science, 2(2), 117-124. https://doi.org/10.15761/JTS.1000127
Ishiguro, Kimiko, et al. "Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines." Journal of translational science vol. 2,2 (2016): 117-124. doi: https://doi.org/10.15761/JTS.1000127
Ishiguro K, Zhu YL, Lin ZP, Penketh PG, Shyam K, Zhu R, Baumann RP, Sartorelli AC, Rutherford TJ, Ratner ES. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines. J Transl Sci. 2016;2(2):117-124. doi: 10.15761/JTS.1000127. Epub 2016 Mar 05. PMID: 27076919; PMCID: PMC4827869.
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J Transl Sci. 2016;2(2):117-124. doi: 10.15761/JTS.1000127. Epub 2016 Mar 05.

Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive ovarian carcinoma cell lines.

Journal of translational science

Kimiko Ishiguro, Yong-Lian Zhu, Z Ping Lin, Philip G Penketh, Krishnamurthy Shyam, Rui Zhu, Raymond P Baumann, Alan C Sartorelli, Thomas J Rutherford, Elena S Ratner

Affiliations

  1. Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, United States.
  2. Department of Pharmacology, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520, United States.

PMID: 27076919 PMCID: PMC4827869 DOI: 10.15761/JTS.1000127

Abstract

Although epithelial ovarian cancers (EOCs) are initially treated with platinum-based chemotherapy, EOCs vary in platinum responsiveness. Cataloging antineoplastic agents according to their effectiveness against platinum-resistant and platinum-sensitive EOC cell lines is valuable for development of therapeutic strategies to avoid platinum inefficacy and to exploit platinum sensitivity. TOV-21G devoid of FANCF expression, OV-90 and SKOV-3 were employed as examples of platinum-sensitive, platinum-intermediate and platinum-resistant cell lines, respectively. Antineoplastic agents examined included mitomycin C, doxorubicin, etoposide, gemcitabine, chlorambucil, paclitaxel, triapine and X-rays. Their effectiveness against cell lines was analyzed by clonogenic assays. Cytotoxic profiles of mitomycin C and carboplatin were similar, with mitomycin C exhibiting greater potency and selectivity against TOV-21G than carboplatin. Cytotoxic profiles of doxorubicin, etoposide and X-rays overlapped with that of carboplatin, while OV-90 overexpressing Rad51 was more resistant to chlorambucil than SKOV-3. The efficacy of paclitaxel and triapine was independent of platinum sensitivity or resistance. Consistent with these cytotoxic profiles, cisplatin/mitomycin C, triapine, and paclitaxel differed in the capacity to induce phosphorylation of H2AX, and produced unique inhibitory patterns of DNA/RNA syntheses in HL-60 human leukemia cells. Paclitaxel and triapine in combination produced additive antitumor effects in M109 murine lung carcinoma. In conclusion, mitomycin C is potentially more effective against Fanconi anemia pathway-deficient EOCs than carboplatin. Doxorubicin and etoposide, because of their overlapping cytotoxic properties with carboplatin, are unlikely to be efficacious against platinum-refractory EOCs. Paclitaxel and triapine are effective regardless of platinum sensitivity status, and promising in combination for both platinum-sensitive and platinum-refractory EOCs.

Keywords: Fanconi anemia pathway; carboplatin; mitomycin C; paclitaxel; platinum responsiveness; triapine

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