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Plicamycin binds to the minor groove of DNA at GC-rich sites, resulting in inhibition of RNA synthesis; this agent also inhibits mRNA expression, resulting in a reduction in protein synthesis. In addition, plicamycin may inhibit bone resorption by down regulating transcription of c-src, an oncogene involved in bone metabolism and resorption.
In vivo, the antitumorigenic activity of Plicamycin (0.2 mg/kg/day) is determined in a xenograft model and observed reduction in tumor volume and weight. No significant mouse body weight loss is observed in Plicamycin-treatment groups, indicating that Plicamycin-associated toxicity is minimal. Plicamycin also increases TUNEL-positive cells in tumor xenografts.
| Cell Experiment | |
|---|---|
| Cell lines | HEp-2 cells and KB cells |
| Preparation method | HEp-2 cells and KB cells are cultured in DMEM 100 U/mL each of Penicillin and Streptomycin and 10% FBS for HEp-2 cells and 5% FBS for KB in a humidified atmosphere containing 5% CO2 at 37°C. Equal numbers of cells are seeded and allowed to attach. At 50-60% confluence, cells are treated with DMSO or indicated concentrations of Plicamycin (50, 100, and 200 nM for HEp-2 cells; 20, 40, and 80 nM for KB cells). After treatment, 30 µL MTS solution is added to each well and cells are incubated for 2 h at 37°C. MTS solution is analyzed using a microplate reader at 490 nm and 690 nm. |
| Concentrations | 50, 100, and 200 nM for HEp-2 cells; 20, 40, and 80 nM for KB cells |
| Incubation time | - |
| Animal Experiment | |
|---|---|
| Animal models | Female nude mice |
| Formulation | - |
| Dosages | 0.2 mg/kg/day, three times per week for 29 days |
| Administration | i.p. |
| Molecular Weight | 1085.15 |
| Formula | C52H76O24 |
| CAS Number | 18378-89-7 |
| Solubility (25°C) | DMSO ≥ 80 mg/mL |
| Storage | Powder -20°C |
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