Effect of stereoisomers related to ICRF-159 on metastasis of B16 melanoma.

The antitumour effects of ICRF-159 and related analogues were evaluated using the B16 melanoma. Treatment of mice with ICRF-159 inhibited tumour growth, while each of the analogues, trans-4,4(1)-(1,2-cyclopropandiyl) bis (2,6-piperazinedione) (trans-5), and cis-4,4(1)-(1,2-cyclopropandiyl) bis (2,6-piperazinedione) (cis-7) independently accelerated primary tumour growth. Pretreatment of B16 melanoma cultures either with ICRF-159 or the analogue cis-7 decreased the yield of lung-colonies following i.v. injection of tumour cells. In contrast, pretreatment of tumour cells with the trans-5 analogue led to an increase in lung colonies. The effect on colony formation in vitro of these analogues correlated with increased growth in vivo, and not with lung colony formation.