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].
RITA 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HCT116 p53+/+
500 nM
16 hours
Induces p53-dependent apoptosis and DNA damage response
Cell Death Dis. 2011 May 19;2(5):e160.
P53-/- HCT116 cells
1 µM
16 hours
RITA did not affect HIF-1α levels.
Mol Cell Biol. 2009 Apr;29(8):2243-53.
MCF-7
1 µM
20 min
Induces DNA damage
Cell Death Dis. 2011 May 19;2(5):e160.
OVCAR4
1 µM
48 hours
Induction of cell death
Cell Death Dis. 2014 Jul 10;5(7):e1318.
Saos-2
500 nM
16 hours
No significant apoptotic or DNA damage response observed
Cell Death Dis. 2011 May 19;2(5):e160.
OVCAR3
1 µM
48 hours
Induction of cell death
Cell Death Dis. 2014 Jul 10;5(7):e1318.
OVCAR5
1 µM
48 hours
Induction of cell death
Cell Death Dis. 2014 Jul 10;5(7):e1318.
H460
1 µM
48 hours
Induction of cell death
Cell Death Dis. 2014 Jul 10;5(7):e1318.
HCT116 p53-/-
500 nM
16 hours
No significant apoptotic or DNA damage response observed
Cell Death Dis. 2011 May 19;2(5):e160.
P53+/+ HCT116 cells
1 µM
16 hours
RITA blocked HIF-1α induction in hypoxia and significantly inhibited VEGF expression.
Mol Cell Biol. 2009 Apr;29(8):2243-53.
MDA-MB-231 cells
1 µM
16 hours
RITA did not induce p53 expression or affect HIF-1α levels.
Mol Cell Biol. 2009 Apr;29(8):2243-53.
MCF-7 cells
1 µM
16 hours
RITA induced p53 expression in both normoxia and hypoxia and blocked hypoxia-induced HIF-1α accumulation.
Mol Cell Biol. 2009 Apr;29(8):2243-53.
HCT116 cells
1.0 µM
24 hours
To study the effects of RITA on cell cycle and apoptosis
Cell Death Differ. 2012 Jun;19(6):980-9.
Mel202 cells
0.25 µM
24 hours
To study RITA-induced Chk2 phosphorylation and its role in apoptosis
Cell Death Differ. 2012 Jun;19(6):980-9.
MCF10A-HRASV12 cells
1 µM
24 hours
To assess the role of Pin1 in RITA-induced apoptosis in RAS-transformed cells, results showed that Pin1 expression levels are a key determinant of cancer cell sensitivity to RITA.
Cell Death Differ. 2013 Feb;20(2):198-208.
HCT116 p53+/+ cells
1 µM
24 hours
To study RITA-induced mitochondrial accumulation of p53 and transcription-independent apoptosis, results showed that RITA treatment caused accumulation of endogenous p53 in the mitochondrial fraction.
Cell Death Differ. 2013 Feb;20(2):198-208.
NTERA-2D1
1 µM
48 hours
Induction of cell death
Cell Death Dis. 2014 Jul 10;5(7):e1318.
HN4-ritaR
5 µM
72 hours
RITA failed to significantly induce apoptosis in HN4-ritaR cells, with sustained autophagy-related protein expression
Redox Biol. 2017 Oct;13:219-227.
HN4-cisR
5 µM
72 hours
RITA failed to significantly induce apoptosis in HN4-cisR cells, with sustained autophagy-related protein expression
Redox Biol. 2017 Oct;13:219-227.
AMC-HN7
5 µM
72 hours
RITA failed to significantly induce apoptosis in AMC-HN7 cells, with sustained or increased autophagy-related protein expression
Redox Biol. 2017 Oct;13:219-227.
AMC-HN6
5 µM
72 hours
RITA failed to significantly induce apoptosis in AMC-HN6 cells, with sustained or increased autophagy-related protein expression
Redox Biol. 2017 Oct;13:219-227.
AMC-HN9
5 µM
72 hours
RITA induced apoptosis in AMC-HN9 cells and decreased autophagy-related protein expression
Redox Biol. 2017 Oct;13:219-227.
AMC-HN4
5 µM
72 hours
RITA induced apoptosis in AMC-HN4 cells and decreased autophagy-related protein expression
Redox Biol. 2017 Oct;13:219-227.
RKO ARID1AOE
129.7 µM and 73.4 µM (IC50)
72 hours
Evaluate the inhibitory effect of RITA on RKO ARID1A-overexpressing cells
Cell Death Dis. 2024 May 29;15(5):375.
RKO ARID1A−/−
18.2 µM (IC50)
72 hours
Evaluate the inhibitory effect of RITA on RKO ARID1A-deficient cells
Cell Death Dis. 2024 May 29;15(5):375.
HCT116 ARID1A−/−
2.0 µM and 3.4 µM (IC50)
72 hours
Evaluate the inhibitory effect of RITA on ARID1A-deficient cells
Cell Death Dis. 2024 May 29;15(5):375.
HCT116 ARID1A+/+
16.7 µM (IC50)
72 hours
Evaluate the inhibitory effect of RITA on ARID1A wild-type cells
Cell Death Dis. 2024 May 29;15(5):375.
HCT116 cells
1 µM
8 hours
RITA treatment promotes the formation of covalently linked TrxR1 oligomers, correlating with cell death
Cell Death Dis. 2015 Jan 22;6(1):e1616.
MCF7 cells
1 µM
8 hours
Analysis of p53 genomic occupancy and gene expression to identify novel p53 target genes
Cell Death Differ. 2012 Dec;19(12):1992-2002.
184A1
1 µM
8 hours
In untransformed cells, RITA treatment did not affect HdmX protein levels.
Cell Death Differ. 2011 Nov;18(11):1736-45.
MCF10A
1 µM
8 hours
In untransformed cells, RITA treatment did not affect HdmX protein levels.
Cell Death Differ. 2011 Nov;18(11):1736-45.
NHDF
1 µM
8 hours
In untransformed cells, RITA treatment did not affect HdmX protein levels.
Cell Death Differ. 2011 Nov;18(11):1736-45.
Saos-2
1 µM
8 hours
In p53-null cells, RITA treatment did not affect HdmX protein levels.
Cell Death Differ. 2011 Nov;18(11):1736-45.
H1299
1 µM
8 hours
In p53-null cells, RITA treatment did not affect HdmX protein levels.
Cell Death Differ. 2011 Nov;18(11):1736-45.
HCT116 TP53-/-
1 µM
8 hours
In p53-null cells, RITA treatment did not affect HdmX protein levels.
Cell Death Differ. 2011 Nov;18(11):1736-45.
H460
0.25 µM
Evaluate the antiproliferative activity of RITA on H460 cells
Nat Chem Biol. 2016 Jan;12(1):22-8.
HCT116
0.25 µM
Evaluate the antiproliferative activity of RITA on HCT116 cells
Nat Chem Biol. 2016 Jan;12(1):22-8.
MCF7
1 µM
8 hours
RITA treatment led to a decrease in HdmX protein levels, while nutlin3a or DMSO control treatment had no such effect.
Cell Death Differ. 2011 Nov;18(11):1736-45.
HCT116
1 µM
8 hours
RITA treatment led to a decrease in HdmX protein levels, while nutlin3a or DMSO control treatment had no such effect.
Cell Death Differ. 2011 Nov;18(11):1736-45.
UKF-NB-3rRITA10μM cells
10 µM
To study the effects of RITA on p53 activation and apoptosis, results showed RITA induced p53 activation and apoptosis
Cell Death Dis. 2012 Apr 5;3(4):e294.
RITA 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
SCID mice
HCT116 and HCT116 TP53-/- xenograft tumors
Intra-tumoral injection
1 mg/kg
Not specified
In p53-positive HCT116 xenograft tumors, RITA treatment led to a decrease in HdmX protein levels, while no such effect was observed in p53-null HCT116 TP53-/- xenograft tumors.
Cell Death Differ. 2011 Nov;18(11):1736-45.
BALB/c nude mice
HCT116 ARID1A+/+ and ARID1A−/− xenograft model
Intravenous injection
10 mg/kg
Daily for 17 days
Evaluate the therapeutic effect of RITA in ARID1A-deficient tumors
Cell Death Dis. 2024 May 29;15(5):375.
BALB/c mice
HCT116 cell-derived tumor xenografts
Intraperitoneal injection
10 mg/kg
Single dose, analyzed after 24 hours
RITA induced p53 and γH2AX phosphorylation in vivo and reduced HIF-1α and VEGF expression.
Mol Cell Biol. 2009 Apr;29(8):2243-53.
Mice
Pin1 knockout mice
Intraperitoneal injection
20 mg/kg
Single dose, sacrificed after 3 hours
To evaluate the effect of Pin1 on doxorubicin-induced mitochondrial accumulation of p53, results showed absence of p53 mitochondrial accumulation in Pin1-deficient cardiac tissues.
Cell Death Differ. 2013 Feb;20(2):198-208.
BALB/c nude mice
HN4-cisR xenograft model
Intraperitoneal injection
RITA 10 mg/kg, 3-MA 25 mg/kg
Once daily for 35 days
RITA plus 3-MA significantly inhibited HN4-cisR tumor growth, increasing oxidative stress and DNA damage
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