Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells

R. Silvestrini, N. Zaffaroni, R. Villa, L. Orlandi, A. Costa

Research output: Contribution to journalArticle

Abstract

The ability of lonidamine, an energolytic derivative of indazolecarboxylic acid, to modulate the cytotoxicity of cisplatin was investigated in human ovarian-cancer cell lines sensitive (A2780) or with experimentally induced resistance (A2780/cp8) to the alkylating agent. A 24-hr post-incubation with 300 μM lonidamine significantly potentiated the activity of a 1-hr cisplatin treatment in both cell lines. In particular, the cisplatin IC50 value was reduced 4-fold in the sensitive line and 5-fold in the resistant line. Flow cytometric analysis showed that, in the resistant cell line, lonidamine alone did not affect cell kinetics, but when given after cisplatin it was able to transform the temporary G2 + M cell accumulation induced by the alkylating agent to a persistent block in S/G2 + M. In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin-induced DNA interstrand cross-links. Our results suggest that lonidamine can positively modulate the anti-tumor activity of cisplatin in ovarian cancer cells and also indicate that the drug is potentially useful in combination therapy including the alkylating agent for ovarian cancer patients.

Original languageEnglish
Pages (from-to)813-817
Number of pages5
JournalInternational Journal of Cancer
Volume52
Issue number5
DOIs
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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