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

Research output: Contribution to journalArticle

Abstract

The ability of mitotane, a DDT derivative with adrcnotoxic activity, and lonidaininc, 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 μg/ml and 0.4 μg/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 μg/ml) and VP16 (IC50, 15 μg/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 potcntiation 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.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalInternational Journal of Oncology
Volume14
Issue number1
Publication statusPublished - 1999

Keywords

  • Adrenocortical carcinoma
  • Drug combinations
  • Lonidamine
  • Mitotane

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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