In vitro cell growth inhibition by metallocene dichlorides.

The in vitro growth-inhibiting potencies of titanocene dichloride (TDC), zirconocene dichloride (ZDC), hafnocene dichloride (HDC), vanadocene dichloride (VDC), and molybdocene dichloride (MDC) against Ehrlich ascites tumor (EAT) cells cultured in viro as permanently growing suspension cultures were determined. The most striking growth-suppression activity was detected for VDC. A VDC concentration as low as 5. 10(-6) mol/l effects a highly significant diminution of cell proliferation. TDC and MDC inhibit cellular growth only concentration of 5 . 10(-4) or 10(-3) mol/l, respectively, whereas ZDC and HDC, which are ineffective against EAT cells in vivo, require higher concentration levels. The growth inhibition is caused by a cytotoxic action of the metallocene dichlorides, as is demonstrated in the case of VDC and TDC by differentiation of live and dead EAT cells by means of the dye lissamine green.