AT101 acetic acid, the R-(-) enantiomer of gossypol acetic acid, binds with Bcl-2, Bcl-xL and Mcl-1 with Ki of 0.32 μM, 0.48 μM and 0.18 μM.
(R)-(-)-Gossypol acetic acid/(R)-(-)-醋酸棉酚 细胞实验
Cell Line
Concentration
Treated Time
Description
References
U937 leukemia cells
20 µM
12 hours
AT-101 significantly increased apoptosis and mitochondrial injury in U937 leukemia cells, accompanied by caspase-3, caspase-9, and PARP cleavage, and cytochrome c release.
Cell Death Dis. 2014 Jan 16;5(1):e998.
Jurkat T-lymphoblastic leukemia cells
20 µM
12 hours
AT-101 significantly increased apoptosis in Jurkat T-lymphoblastic leukemia cells, accompanied by caspase-3, caspase-9, and PARP cleavage, and cytochrome c release.
Cell Death Dis. 2014 Jan 16;5(1):e998.
HL-60 promyelocytic leukemia cells
20 µM
12 hours
AT-101 significantly increased apoptosis in HL-60 promyelocytic leukemia cells, accompanied by caspase-3, caspase-9, and PARP cleavage, and cytochrome c release.
Cell Death Dis. 2014 Jan 16;5(1):e998.
HUVECs
5 µM
18 hours
AT-101 significantly enhanced the inhibitory effect of CDDP on the migration of HUVECs
Drug Des Devel Ther. 2015 Jun 8;9:2887-910.
A2780
5 µM
24 hours
GAA significantly reduced mitochondrial activity in A2780 cells, including basal OCR, ATP production, and Maximal OCR.
J Transl Med. 2023 Jul 26;21(1):504.
SKOV3
5 µM
24 hours
GAA significantly reduced mitochondrial activity in SKOV3 cells, including basal OCR, ATP production, and Maximal OCR.
J Transl Med. 2023 Jul 26;21(1):504.
Primary human leukemia cells
20 µM
24 hours
AT-101 significantly increased apoptosis in primary human leukemia cells, accompanied by caspase-3, caspase-9, and PARP cleavage, and cytochrome c release.
Cell Death Dis. 2014 Jan 16;5(1):e998.
MM-B1
1.56–25 µM
24, 48, and 72 hours
AT-101 significantly inhibited the survival of MM-B1 cells, with IC50 values of 9.30 μM at 48 hours and 5.59 μM at 72 hours.
Front Pharmacol. 2018 Nov 6;9:1269.
H-Meso-1
1.56–25 µM
24, 48, and 72 hours
AT-101 significantly inhibited the survival of H-Meso-1 cells, with IC50 values of 9.24 μM at 48 hours and 2.66 μM at 72 hours.
Front Pharmacol. 2018 Nov 6;9:1269.
MM-F1
1.56–25 µM
24, 48, and 72 hours
AT-101 significantly inhibited the survival of MM-F1 cells, with IC50 values of 9.32 μM at 48 hours and 5.10 μM at 72 hours.
Front Pharmacol. 2018 Nov 6;9:1269.
U87MG
15 µM
48 hours
To investigate the effects of AT-101 on protein expression in U87MG cells, results showed a significant downregulation of mitochondrial-related proteins.
Autophagy. 2018;14(10):1693-1709.
U343
15 µM
48 hours
To investigate the effects of AT-101 on protein expression in U343 cells, results showed a significant downregulation of mitochondrial-related proteins.
Autophagy. 2018;14(10):1693-1709.
A549 cells
5 µM
48 hours
AT-101 significantly enhanced the inhibitory effect of CDDP on the proliferation of A549 cells
Drug Des Devel Ther. 2015 Jun 8;9:2887-910.
Human non-small cell lung cancer A549 cells
5 µM
6 hours
To evaluate the effects of sequential treatment with AT-101 and cisplatin (CDDP) on the proliferation, migration, and apoptosis of A549 cells. The results showed that the sequential treatment significantly inhibited cell proliferation and migration and induced apoptosis.
Drug Des Devel Ther. 2014 Dec 12;8:2517-29.
VCaP cells
1-10 µM
72 hours
To evaluate the effect of AT-101 on VCaP cell viability, results showed that AT-101 dose-dependently decreased VCaP cell viability after 72 hours
Neoplasia. 2007 Dec;9(12):1030-7.
PC-3 cells
1-10 µM
72 hours
To evaluate the effect of AT-101 on PC-3 cell viability, results showed that AT-101 dose-dependently decreased PC-3 cell viability after 72 hours
Neoplasia. 2007 Dec;9(12):1030-7.
PC-3 (prostate cancer cells)
8.72 ± 0.30 µM (IC50)
72 hours
Evaluate the cytotoxicity of Gos/cRGD-LP on PC-3 cells, results showed that the IC50 of Gos/cRGD-LP was 9.53 ± 0.26 μM, significantly higher than that of free drug, indicating stronger cytotoxicity.
Int J Nanomedicine. 2022 Jan 14;17:227-244.
HCT-116 (colon cancer cells)
6.32 ± 0.40 µM (IC50)
72 hours
Evaluate the cytotoxicity of Gos/cRGD-LP on HCT-116 cells, results showed that the IC50 of Gos/cRGD-LP was 8.93 ± 0.41 μM, significantly higher than that of free drug, indicating stronger cytotoxicity.
Int J Nanomedicine. 2022 Jan 14;17:227-244.
(R)-(-)-Gossypol acetic acid/(R)-(-)-醋酸棉酚 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Mouse model intraperitoneally transplanted with #40a cells
Intraperitoneal injection
0.1 mg
Once a week, up to 17 weeks
AT-101 significantly increased the median survival time of mice (7 weeks vs. 4.5 weeks) and reduced the risk of tumor development.
Front Pharmacol. 2018 Nov 6;9:1269.
SCID mice
VCaP prostate cancer xenograft model
Oral
15 mg/kg
5 days per week, continuous treatment
To evaluate the efficacy of AT-101 in combination with surgical castration in delaying the onset of androgen-independent prostate cancer growth, results showed that AT-101 combined with surgical castration significantly delayed the onset of androgen-independent prostate cancer growth
Neoplasia. 2007 Dec;9(12):1030-7.
BALB/c Nude mice
PC-3 tumor model
Intravenous injection
15 mg/kg
Once every three days, for 6 times in total
Evaluate the antitumor effect of Gos/cRGD-LP in the PC-3 tumor model, results showed that Gos/cRGD-LP significantly inhibited tumor growth, with a tumor inhibition rate of over 74%.
Int J Nanomedicine. 2022 Jan 14;17:227-244.
BALB/c Nude mice
A2780 cell subcutaneous xenograft model
Intraperitoneal injection
30 mg/kg
Every other day for 3 weeks
GAA significantly inhibited the growth of A2780 cell subcutaneous xenografts and did not cause weight loss or liver and kidney function impairment in mice.
J Transl Med. 2023 Jul 26;21(1):504.
BALB/c Nude mice
A549 xenograft model
Oral gavage
35 mg/kg/day
For 10 consecutive days
To evaluate the effects of sequential treatment with AT-101 and cisplatin (CDDP) on tumor growth in the A549 xenograft model. The results showed that the sequential treatment significantly inhibited tumor growth and enhanced the expressions of Bcl-2 and Bcl-xL by downregulating the APE1/STAT3 signaling pathway.
Drug Des Devel Ther. 2014 Dec 12;8:2517-29.
BALB/c Nude mice
A549 xenograft model
Oral and intraperitoneal injection
35 mg/kg/day
10 days
Combination therapy of AT-101 and CDDP significantly inhibited tumor angiogenesis and tumor cell proliferation
Drug Des Devel Ther. 2015 Jun 8;9:2887-910.
NOD/SCID mice
U937 xenograft model
Intraperitoneal injection
50 mg/kg
Five times per week for 60 days
AT-101 significantly inhibited tumor growth in the U937 xenograft mouse model, accompanied by RhoA/ROCK1/PTEN signaling activation and Akt inactivation.
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