Information
Ansamitocin p-3 (Maytansinol isobutyrate, NSC292222, Antibiotic C 15003P3) is a potent inhibitor of tubulin polymerization with IC50 of 3.4 μM.
In vitro
Ansamitocin p-3 at 5 μM completely inhibits the polymerization of tubulin isolated from bovine brains, but in contrast to VCR, Ansamitocin p-3 at a high concentration of 80 μM does not leads to the aggregation of tubulin. Ansamitocin p-3 at 16 μM also potently depolymerizes the polymerized tubulin (IC50 = 3.8 μM). The addition of Ansamitocin p-3 to culture cells blocks the morphological alteration of AC cells from fibroepithelioid to a glial cell type caused by the exposure to a certain concentration of dibutyryl cyclic adenosine 3\':5\'-monophosphate. In addition, Ansamitocin p-3 treatment at 16 nM causes the well-defined network of cytoplasmic microtubules of A31 cells rapidly dispersed. Short-term Ansamitocin p-3 treatment also inhibits the synthesis of DNA in A31 cells or KB cells. These results confirm that Ansamitocin p-3 acts by interfering with the microtubule assembly system, thus resulting in an inhibition of mitotic spindle fiber formation and, ultimately, cytokilling. Ansamitocin p-3 displays potent cytotoxicity against A-549, HT-29, and MCF-7 cells in a dose-dependent manner with ED50 of 4 ×10-7, 4 × 10-7, and 2 × 10-6 μg/mL, respectively. Ansamitocin p-3 also exhibits cytotoxicity against HCT-116 cells with a much low EC50 of 0.081 nM. Ansamitocin p-3 enhances the effect of radiation both in Drosophila cells and human cancer cells in a p53 dependent manner.
In vivo
Ansamitocin p-3 treatment (>1 μg) significantly suppresses the growth of leukemia SN36, and induces an increased arrest in metaphase of P388 leukemia cells. Ansamitocin p-3 treatment at 25 μg/kg/day significantly prolongs the survival time of mice bearing i.p. B16 melanoma by 130%. Ansamitocin p-3 treatment also significantly prolongs the survival time of mice bearing Ehrlich ascites carcinoma, Sarcoma 180, and P815 mastocytoma, while slightly prolongs the survival time of mice bearing ascites MOPC-104E myeloma,leukemia L1210, and leukemia C1498.
Cell Research(from reference)
Cell lines：A31 and KB
Concentrations：Dissolved in DMSO, final concentrations ~10 μM
Incubation Time：~24 hours
