Phenotypic Reversion Induced by Anthracyclines in ras Oncogene-Expressed Cells; Structure-Activity Relationships

Abstract

Several antitumor anthracyclines, including those in preclinical stages, were examined for their action in reversing tumorous phenotypes of H-or K-ras 3T3 cells (NIH3T3 cells transformed by human H-or K-ras oncogene) into normal phenotypes, such as flattened cell morphology, anchorage dependent cell growth, etc. (referred to as anti-ras activity). The study elucidated relationships between the chemical structure of anthracyclines and the anti-ras activity. The human tumor cell line T24, which has a mutated H-ras gene, responded to the anthracyclines, as did K-or H-ras 3T3 cells, in respect to the phenotypic alterations. Pirarubicin was more than 4 times as active as aclarubicin in inhibiting the growth of solid tumors of K-ras 3T3 cells in nude mice, possibly reflecting a difference in anti-ras activity between the two antibiotics. © 1994, The Pharmaceutical Society of Japan. All rights reserved.