Effects of hycanthone on rapidly proliferating cells

Susan M. Sieber, Jacqueline Whang-Peng, David G. Johns, Richard H. Adamson

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The effects of hvcanthone on various types of rapidly proliferating tissue, including tumor cells in vitro and in vivo, phytohemagglutinin (PHA)-stimulated lymphocytes, and embryonic cells, have been investigated. Hycanthone was cytotoxic to several tumor cell lines in tissue culture and exerted antitumor activity in vivo against Walker 256 carcinosarcoma, leukemia L1210 and mast cell P815. Human PHA-stimulated lymphocytes incubated in the presence of hycanthone showed a 50 per cent depression in mitotic index, and a marked increase in number of chromosomal aberrations. Hycanthone administered to pregnant mice was not teratogenic, but its embryotoxicity was manifested by an increased incidence of intrauterine death and a decrease in average fetal body weights. Mechanism studies have shown that hycanthone inhibits both DNA and RNA, but not protein synthesis, in human PHA-stimulated lymphocytes. Furthermore, hycanthone was found to inhibit aldehyde oxidase and this inhibition was greater than that previously reported for the N-alkylphenothiazines. These studies suggest that hycanthone may have promise as an antitumor agent, either alone or in combination with antitumor agents known to be inactivated by aldehyde oxidase.

Original languageEnglish
JournalBiochemical Pharmacology
Volume22
Issue number11
DOIs
Publication statusPublished - Jun 1 1973
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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