Effect of lonidamine on the cytotoxic activity of cisplatin, mitomycin C and BCNU in human ovarian and colon carcinoma cells

N. Zaffaroni, A. Bearzatto, D. Gornati, R. Silvestrini

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The ability of lonidamine (LND), an energolytic derivative of indazole carboxylic acid, to modulate the cytotoxic activity of cisplatin (CDDP), mitomycin C (MMC) and BCNU was investigated in established cell lines of human ovarian and colon cancers. A 24 hour post-incubation with LND significantly potentiated the activity of a 1 hour CDDP treatment in both the sensitive (A2780) and resistant (A2780/Cp8) ovarian cell lines. Flow cytometric analysis showed that, in the resistant cell line, LND transformed the temporary G2+M cell accumulation induced by CDDP into a persistent block in S/G2+M phases. Again, in the A2780/Cp8 cells, LND markedly enhanced the accumulation of DNA interstrand crosslinks (DNA ISC) induced by the alkylating agent. As regards the colon cancer cell lines, a 24 hour postincubation with LND enhanced the cytotoxicity of a 1 hour exposure to MMC or BCNU in both LoVo and HT29 cells. Moreover, flow cytometric data indicated that LND generally stabilized the cell cycle perturbations induced by MMC and BCNU in the two cell lines. On the whole, our results show that LND can positively modulate the activity of conventional anticancer agents and indicate this compound to be an attractive candidate for multidrug combination therapies in ovarian and colon cancer.

Original languageEnglish
Pages (from-to)773-778
Number of pages6
JournalInternational Journal of Oncology
Volume4
Issue numberSUPPL.
Publication statusPublished - 1994

Fingerprint

Carmustine
Mitomycin
Cisplatin
Colon
Carcinoma
Colonic Neoplasms
Cell Line
Ovarian Neoplasms
Indazoles
HT29 Cells
Transformed Cell Line
G2 Phase
Alkylating Agents
Carboxylic Acids
lonidamine
Cell Division
Antineoplastic Agents
Cell Cycle
DNA

Keywords

  • BCNU
  • cisplatin
  • lonidamine
  • mitomycin C

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Effect of lonidamine on the cytotoxic activity of cisplatin, mitomycin C and BCNU in human ovarian and colon carcinoma cells. / Zaffaroni, N.; Bearzatto, A.; Gornati, D.; Silvestrini, R.

In: International Journal of Oncology, Vol. 4, No. SUPPL., 1994, p. 773-778.

Research output: Contribution to journalArticle

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