RT Journal Article SR Electronic T1 The DNA Minor Groove-alkylating Cyclopropylpyrroloindole Drugs Adozelesin and Bizelesin Induce Different DNA Damage Response Pathways in Human Colon Carcinoma HCT116 Cells1 JF Molecular Cancer Therapeutics JO Mol Cancer Ther FD American Association for Cancer Research SP 651 OP 659 VO 2 IS 7 A1 Cao, Pei-rang A1 McHugh, Mary M. A1 Melendy, Thomas A1 Beerman, Terry YR 2003 UL http://mct.aacrjournals.org/content/2/7/651.abstract AB As members of the cyclopropylpyrroloindole family, adozelesin and bizelesin cause genomic DNA lesions by alkylating DNA. Adozelesin induces single-strand DNA lesions, whereas bizelesin induces both single-strand lesions and double-strand DNA cross-links. At equivalent cytotoxic concentrations, these agents caused different biological responses. Low adozelesin concentrations (e.g., 0.5 nm) induced a transient S-phase block and cell cycle arrest in G2-M, as well as increased induction of p53 and p21, whereas a high drug concentration (e.g., 2.5 nm) caused apoptosis but no p21 induction. In contrast, both low and high bizelesin concentrations enhanced p53 and p21 induction and triggered G2-M cell cycle arrest and eventual senescence without significant apoptotic cell death. However, in cells lacking p21, bizelesin, as well as adozelesin, triggered apoptosis, indicating that p21 was crucial to sustained bizelesin-induced G2-M arrest. Thus, despite similar abilities to alkylate DNA, the chemotherapeutic agents adozelesin and bizelesin caused a decrease in HCT116 tumor cell proliferation by different pathways (i.e., adozelesin induced apoptosis, and bizelesin induced senescence).