Abstract | BACKGROUND: 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.
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Authors | Junichi Koh, Tetsuro Kubota, Tomofusa Migita, Sadanori Abe, Mitsumasa Hashimoto, Yoichiro Hosoda, Masaki Kitajima |
Journal | Breast cancer (Tokyo, Japan)
(Breast Cancer)
Vol. 9
Issue 1
Pg. 50-4
( 2002)
ISSN: 1340-6868 [Print] Japan |
PMID | 12196722
(Publication Type: Journal Article)
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Chemical References |
- Alkaloids
- Antineoplastic Agents
- Estrogens
- 7-hydroxystaurosporine
- Doxorubicin
- Cyclophosphamide
- Protein Kinase C
- Staurosporine
- Fluorouracil
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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)
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