Efficacy of Ionidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

Graziella Pratesi, Michelandrea De Cesare, Franco Zunino

Research output: Contribution to journalArticlepeer-review

Abstract

Lonidamine is an antitumor agent with a peculiar mechanism of action, since it differentially impairs the energy metabolism of normal and neoplastic cells. We investigated the effects of lonidamine on the activity of DNA-damaging antitumor agents against the MX-1 human breast carcinoma xenograft. Athymic mice bearing measurable s.c. tumors were treated by a single injection of doxorubicin (i.v.), cyclophosphamide (i.v.), or cisplatin (i.p.) followed by repeated daily injections of lonidamine (i.p. or p.o.). A potentiation of the activity of all these DNA-damaging drugs was achieved when each was given in combination with lonidamine, but for doxorubicin and cyclophosphamide the increase in antitumor activity paralleled the increase in lethal toxicity. In contrast, a therapeutic advantage of the combination was achieved for cisplatin and lonidamine as compared with cisplatin alone. Indeed, 6 mg/kg of cisplatin plus lonidamine cured all tumors, whereas the maximum tolerated dose of cisplatin alone (12 mg/kg) cured only six of eight tumors. In addition, the study indicated that the duration of lonidamine administration after injection of the cytotoxic drug influenced the tumor response and that prolonged treatment resulted in greater efficacy. These results document the ability of lonidamine to modulate the pharmacological activity of DNA-damaging drugs, thus suggesting that lonidamine may be a clinically useful cisplatin modulator.

Original languageEnglish
Pages (from-to)123-128
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume38
Issue number2
Publication statusPublished - 1996

Keywords

  • Cisplatin
  • Cyclophosphamide
  • Doxorubicin
  • Human tumor xenograft
  • Lonidamine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology

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