The quinolinone derivative vesnarinone potentiates the cytotoxicity of doxorubicin in HL-60 leukemia cells

Manabu Yamamoto, Yoshihiko Maehara, Yoshihisa Sakaguchi, Tetsuya Kusumoto, Hideo Baba, Keizo Sugimachi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Vesnarinone, (3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone), a quinolinone derivative, is a positive inotropic agent. We examined the cytotoxicity either by vesnarinone alone or in combination with doxorubicin (DXR), in vitro. The cytotoxic effect of vesnarinone against HL-60 cells did not increase, even at concentrations as high as (50 μg/ml). The cytotoxicity of DXR, however, was enhanced after being combined with 30 μg/ml of vesnarinone. The intracellular level of DXR increased when DXR was administered after incubation with vesnarinone and the efflux of DXR was delayed when the cells were incubated in the presence of vesnarinone after DXR exposure. Flow cytometry showed that the combination of DXR and vesnarinone increased the cell population below the G0/G1 region. Vesnarinone induced DNA ladder formation, but only when these cells were incubated for 72 h, while in addition, when DXR was combined with vesnarinone, the DNA ladder formation was enhanced. Based on the above findings, we thus conclude that the cytotoxicity of DXR was enhanced when combined with vesnarinone.

Original languageEnglish
Pages (from-to)53-57
Number of pages5
JournalInternational journal of oncology
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 1997

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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