Modulation of cytotoxic drug activity by mitotane and lonidamine in human adrenocortical carcinoma cells.

  • Authors:
    • R Villa
    • L Orlandi
    • A Berruti
    • L Dogliotti
    • N Zaffaroni
  • View Affiliations

  • Published online on: Friday, January 1, 1999
  • Pages: 133-141
  • DOI: 10.3892/ijo.14.1.133

Abstract

The ability of mitotane, a DDT derivative with adrenotoxic activity, and lonidamine, an energolytic derivative of indazole-carboxylic acid, to modulate the cytotoxic activity of doxorubicin, epidoxorubicin, cisplatin and VP16 was investigated in a human adrenocortical carcinoma cell line (SW13). A marked variability in cellular response to a 1-h treatment with the individual anticancer agents was observed. The concentrations able to inhibit SW13 cell proliferation by 50% (IC50) were 0.45 microg/ml and 0.4 microg/ml for doxorubicin and epidoxorubicin, respectively, thus indicating a relative sensitivity to anthracyclines. Conversely, the SW13 cell line displayed a marked resistance to cisplatin (IC50, 13.9 microg/ml) and VP16 (IC50, 15 microg/ml). When cells were exposed to anticancer drugs and mitotane simultaneously or in sequence, a positive modulation of anthracycline cytotoxic effects was observed. Although to a lesser extent, mitotane also increased cisplatin activity. Conversely, no potentiation was observed when mitotane was combined with VP16. Lonidamine slightly increased the cytotoxicity of epirubicin and cisplatin as individual agents. Moreover, a supra-additive effect of the three-drug (epidoxorubicin-cisplatin-lonidamine) combination was observed.
Journal Cover

January 1999
Volume 14 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
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APA
Villa, R., Orlandi, L., Berruti, A., Dogliotti, L., & Zaffaroni, N. (1999). Modulation of cytotoxic drug activity by mitotane and lonidamine in human adrenocortical carcinoma cells.. International Journal of Oncology, 14(1), 133-141.
MLA
Villa, Orlandi, Berruti, Dogliotti, and N Zaffaroni. "Modulation of cytotoxic drug activity by mitotane and lonidamine in human adrenocortical carcinoma cells.." International Journal of Oncology International Journal of Oncology 14.1 (1999): 133-141.
Chicago
Villa, Orlandi, Berruti, Dogliotti, and N Zaffaroni. "Modulation of cytotoxic drug activity by mitotane and lonidamine in human adrenocortical carcinoma cells.." International Journal of Oncology International Journal of Oncology 14 no. 1 (1999): 133-141.