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.