ANTICANCER QUINONES INDUCE PRB-PREVENTABLE G(2) M CELL-CYCLE ARREST AND APOPTOSIS/

Reactive oxygen species generated during the metabolism of the antitum or quinone 3,6-diaziridinyl-1,4-benzoquinone (DZQ) in human colonic ca rcinoma HCT116 cells lead to the induction of p21 (WAF1, Cip1, or sdi1 ), an upstream regulator of the retinoblastoma gene product pRb involv ed G(1) cell cycle control. We here demonstrate that the cell cycle wa s arrested in G(2)/M phase following supplementation with DZQ of human osteosarcoma Saos-2 cells (lacking both p53 and pRb) and HCT116 cells . DZQ also induced p21 and apoptosis in Saos-2 cells. The transfection of the Rb gene into Saos-2 cells did not alter the level of p21 induc tion, but changed cell cycle arrest into G(1) phase and prevented apop tosis. These findings suggest that quinones may lead to a p53-independ ent and pRb-preventable G(2)/M arrest and apoptosis, which correlate w ith p21 induction. (C) 1998 Elsevier Science Inc.