Menogaril, an anthracycline compound with a novel mechanism of action: Cellular pharmacology

Konstanty Wierzba, Yoshikazu Sugimoto, Ken ichi Matsuo, Toshiyuki Toko, Setsuo Takeda, Yuji Yamada, Shigeru Tsukagoshi

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9 Citations (Scopus)

Abstract

Menogaril, an anthracycline compound possessing a significant antitumor activity after both po and iv administration, has been introduced into clinical trials. However, its mechanisms of action has not been clarified yet. This study revealed that its cytotoxicity correlated very well with the inhibition of macromolecular synthesis, indicating the involvement of interaction with DNA. The spectrophotometric study showed a weaker binding of this compound to calf thymus DNA when compared to that of doxorubicin (adriamycin). Despite the lower binding affinity of menogaril to DNA, pronounced DNA cleavage was observed in an intact cell system, indicating that the character of the interaction with DNA is different from intercalation. In contrast to doxorubicin, menogaril is extensively localized in the cytoplasm. The cytoplasmic localization prompted us to study its effect on cytoskeleton proteins. It was found that menogaril inhibited the initial polymerization rate of tubulin, indicating a possible contribution of this process to the overall cytotoxicity of menogaril.

Original languageEnglish
Pages (from-to)842-849
Number of pages8
JournalJapanese Journal of Cancer Research
Volume81
Issue number8
Publication statusPublished - 1990 Aug
Externally publishedYes

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Keywords

  • Anthracycline compound
  • Interaction with DNA
  • Menogaril
  • Microtubular system

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wierzba, K., Sugimoto, Y., Matsuo, K. I., Toko, T., Takeda, S., Yamada, Y., & Tsukagoshi, S. (1990). Menogaril, an anthracycline compound with a novel mechanism of action: Cellular pharmacology. Japanese Journal of Cancer Research, 81(8), 842-849.