Anticancer quinones induce pRb-preventable G2/M cell cycle arrest and apoptosis

Reactive oxygen species generated during the metabolism of the antitumor quinone 3,6-diaziridinyl-1,4-benzoquinone (DZQ) in human colonic carcinoma HCT116 cells lead to the induction of p21 (WAF1, Cip1, or sdi1), an upstream regulator of the retinoblastoma gene product pRb involved G(1) cell cycle control. We here demonstrate that the cell cycle was 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 induction, but changed cell cycle arrest into G(1) phase and prevented apoptosis. These findings suggest that quinones may lead to a p53-independent and pRb-preventable G(2)/M arrest and apoptosis, which correlate with p21 induction. (C) 1998 Elsevier Science Inc.