RITA induced both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks. It is MDM2-p53 interaction inhibitor and activatesp53 expression.
RITA (NSC 652287), a representative of a series of thiophene derivatives, is a DNA damage inducing agent that induces both DNA-protein and DNA-DNA cross-links with no detectable DNA single-strand breaks and exhibits potent and selective antitumor activity against several tumor cell lines[3]. The renal carcinoma cell line A498 treated with 10 nM NSC 652287 exhibited cell cycle arrest in G(0)-G(1) and G(2)-M, with increased p53 and p21(WAF1) protein. NSC 652287 at higher concentrations still induced p53 elevation but with p21(WAF1) reduction and massive apoptosis[3]. MCF-7 and MDA-MB-231 cells were treated with RITA (1 μM) for 24 h in normoxia and hypoxia (1% O2) and there was a clear increase in rounding and displacement of cells from monolayers in tissue culture, indicative of apoptosis, to a similar extent in normoxia and hypoxia[4]. RITA exhibits potent antileukemic properties against p53-null chronic myeloid leukemia (CML)-derived K562 cells by triggering apoptosis through caspase-9 and caspase-3 activation and poly (ADP-ribose) polymerase cleavage, in a dose- and time-dependent manner (1,2 and 4 µM)[5].
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