Phenotypic reversion induced by anthracyclines in ras oncogene-expressed cells; structure-activity relationships.
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.
Kanbe
T
T
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Tsuchiya
K S
KS
Hori
M
M
Ekimoto
H
H
Takahashi
Y
Y
Takeuchi
T
T
D016475:3T3 Cells; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology*; D010641:Phenotype; D013329:Structure-Activity Relationship; D001749:Urinary Bladder Neoplasms / Q000473:pathology
D000903:Antibiotics, Antineoplastic