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 G1 cell cycle control. We here demonstrate that the cell cycle was arrested in G2/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 G1 phase and prevented apoptosis. These findings suggest that quinones may lead to a p53-independent and pRb-preventable G2/M arrest and apoptosis, which correlate with p21 induction.
Qiu
X B
XB
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, Los Angeles 90033, USA.
Schönthal
A H
AH
Cadenas
E
E
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001388:Aziridines / Q000627:therapeutic use*; D016227:Benzoquinones / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D016160:Retinoblastoma Protein / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D016160:Retinoblastoma Protein; C009970:ethylenimine quinone; D006861:Hydrogen Peroxide