HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

UCN-01 (7-hydroxystaurosporine) inhibits the growth of human breast cancer xenografts through disruption of signal transduction.

AbstractBACKGROUND:
7-Hydroxystaurosporine (UCN-01), originally isolated as a phospholipid-dependent protein kinase C inhibitor, has been shown to have antitumor activity against several human cancer cell lines. UCN-01 inhibits cell cycle progression from the G1 to S phase by inhibition of cyclin-dependent kinase (CDK) activity and induction of intrinsic CDK inhibitor protein, leading to dephosphorylation of retinoblastoma (Rb) protein.
MATERIALS AND METHODS:
The antitumor activity of UCN-01 has been investigated against three human breast carcinoma strains serially transplanted into nude mice, including estrogen-dependent MCF-7, Br-10, and estrogen-independent MX-1. When the inoculated tumors started growing exponentially, UCN-01 (7.5 mg/kg) was administered intraperitoneally on five consecutive days a week for 2 weeks. The antitumor effect was evaluated as the lowest T/C ratio (%) during the experiments, where T was the relative mean tumor weight of the treated group and C was that of the control group. At the end of UCN-01 administration expression of p21, a protein of the CDK inhibitor family, and phosphorylated and dephosphorylated Rb protein was detected by Western blotting using treated and control tumors.
RESULTS:
UCN-01 had activity against MCF-7 and Br-10, with the lowest T/C ratios of 25.0% and 27.0%, respectively, while MX-1 was resistant to UCN-01 with a T/C ratio of 65.9%. The antitumor spectrum of UCN-01 was different from that of other conventional agents such as doxorubicin and cyclophosphamide which were ineffective against Br-10 but were active against MX-1. Although p21 was induced in three tested strains by UCN-01, little dephosphorylated Rb protein was expressed in MX-1 compared with Br-10 and MCF-7 (in vitro).
CONCLUSION:
UCN-01 appeared to be a promising agent for the treatment of breast cancer, with a different mode of action and antitumor spectrum from other currently available antitumor drugs.
AuthorsJunichi Koh, Tetsuro Kubota, Tomofusa Migita, Sadanori Abe, Mitsumasa Hashimoto, Yoichiro Hosoda, Masaki Kitajima
JournalBreast cancer (Tokyo, Japan) (Breast Cancer) Vol. 9 Issue 1 Pg. 50-4 ( 2002) ISSN: 1340-6868 [Print] Japan
PMID12196722 (Publication Type: Journal Article)
Chemical References
  • Alkaloids
  • Antineoplastic Agents
  • Estrogens
  • 7-hydroxystaurosporine
  • Doxorubicin
  • Cyclophosphamide
  • Protein Kinase C
  • Staurosporine
  • Fluorouracil
Topics
  • Alkaloids (administration & dosage, pharmacology)
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacology)
  • Blotting, Western
  • Breast Neoplasms (metabolism)
  • Cyclophosphamide (administration & dosage, pharmacology)
  • Dose-Response Relationship, Drug
  • Doxorubicin (administration & dosage, pharmacology)
  • Drug Synergism
  • Estrogens
  • Female
  • Fluorouracil (administration & dosage, pharmacology)
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms, Hormone-Dependent (metabolism)
  • Protein Kinase C (antagonists & inhibitors)
  • Signal Transduction (drug effects)
  • Staurosporine (analogs & derivatives)
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Cells, Cultured (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: