7-Hydroxycoumarin inhibits oncogene-induced transformation of murine fibroblasts.
7-Hydroxycoumarin (7-HC) is a naturally occurring substance with a variety of biological activities, e.g. antitumoral and immunomodulatory action. The potential mechanisms of 7-HC action on tumor cells have been investigated in a model of mouse fibroblasts transformed by distinct retroviral vectors carrying the oncogenes myc and ras. Treatment of the different oncogenic transformants with 7-HC in non-cytotoxic concentrations causes a strong inhibition of their proliferative capacity as measured by growth curves. Furthermore, incubation of the ras and myc transformants with 7-HC abrogated soft agar colony formation when compared to untreated cultures. These changes in cell growth characteristics of the various oncogene-transformed mouse fibroblasts were transient, since removal of 7-HC from the cultures caused a reappearance of the transformed properties of these cells within 6 days. The 7-HC-mediated inhibition of the proliferative capacity of the transformants was preceded by a selective down-regulation of oncogene expression. These data suggest that 7-HC causes a reversible inhibition of ras- and myc-induced neoplastic properties in transformed fibroblasts by selective down-regulation of retroviral RNA levels.
Seliger
B
B
III. Medical Clinic, Department of Hematology/Oncology, Mainz, Germany.
Pettersson
H
H
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016259:Genes, myc; D011905:Genes, ras; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014468:Umbelliferones / Q000494:pharmacology*
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014468:Umbelliferones; C031477:7-hydroxycoumarin