CYTOTOXIC EFFECT OF HINOKITIOL AND TROPOLONE ON THE GROWTH OF MAMMALIAN-CELLS AND ON BLASTOGENESIS OF MOUSE SPLENIC T-CELLS

Hinokitiol (1) and tropolone (11) showed characteristic cytotoxic effects in vitro on five kinds of human and murine cell lines and blastic lymphocytes from mouse splenocytes. The cytotoxic effect of I on the growth of murine and human tumor cell lines, including RLmale-1, MH134, HL60, K562 and KATO-III was definite when examined by thymidine incorporation into DNA and its 50% inhibitory concentration (IC50) on all cells was 0.3-0.6 mug/ml. Compound II also showed comparable cytotoxic effects on these cell lines, indicating a little lower activity when compared to I. Furthermore, I and II also completely suppressed the [H-3]thymidine ([H-3]TdR) incorporation of mitogen-induced blastic lymphocytes. The suppressive activity on mouse lymphocyte proliferative response to concanavaline-A was also found with both compounds at a low concentration of 0.32 mug/ml. As compound I is known to be of fairly low toxicity (LD50:453+24 mg/kg in mice), the antitumor and immuno-suppressive effect of hinokitiol (I) should be further investigated.