AT-101 (R-(-)-gossypol acetic acid) is a polyphenolic compound isolated from cottonseeds. AT-101 induces Apoptosis through activation of caspase-9, -3, and -7 in VCaP cells. It inhibits Bcl-2 by acting as a BH3 mimetic and disrupts the heterodimerization of Bcl-2 with proapoptotic family members. AT-101 was found to mimic the proapoptosis proteins and is able to bind to the BH3 domains of Bcl-2, Mcl-1, and Bcl-xL. AT-101 has been shown to be therapeutically active as a single agent in several mouse models including breast, prostate, colon, and non-small cell lung cancer. We demonstrate that AT-101 administration delays the onset of androgen-independent prostate cancer in vivo. The use of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer.
Cell Experiment | |
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Cell lines | HDMEC, OSCC3, UM-SCC-17B, UM-SCC-74A cells line |
Preparation method | SRB assay Sulforhodamine B (SRB) cytotoxicity assays were done as described (25). Briefly, cells were seeded at 2×103 cells per well of 96-well plates, allowed to attach overnight, and treated with AT101 and/or taxotere for 72–96 hours. Cells were fixed with 10% trichloroacetic acid, stained with 0.4% SRB (Sigma-Aldrich, St. Louis, MO) in 1% acetic acid, and plates were read in a microplate reader at 560 nm (GENios; Tecan, Graz, Austria). Test results were normalized against initial plating density and drug-free controls. Data were obtained from triplicate wells per condition and is representative of three independent experiments. |
Concentrations | 0~100µM |
Incubation time | 72-96 h |
Animal Experiment | |
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Animal models | SCID Mouse Model of Human Tumor Angiogenesis |
Formulation | resuspended in carboxymethyl cellulose and sonicated for 30 minutes |
Dosages | 10mg/kg daily or 70mg/kg weekly |
Administration | orally |
Molecular Weight | 518.56 |
Formula | C30H30O8 |
CAS Number | 90141-22-3 |
Solubility (25°C) | DMSO Ethanol |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
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