Action of low calcemic 1alpha,25-dihydroxyvitamin D3 analogue EB1089 in head and neck squamous cell carcinoma

Autor: Roberto Lin, Martin J. Black, Taiqui Wang, José Prudencio, John H. White, Naciba Benlimame, Moulay A. Alaoui-Jamali, Yolande Bastien, Naotake Akutsu
Rok vydání: 2001
Předmět:
Cyclin-Dependent Kinase Inhibitor p21
Male
Cancer Research
medicine.medical_specialty
Cytoplasm
Time Factors
Tumor suppressor gene
Calcitriol
Blotting
Western
Antineoplastic Agents
Cell Cycle Proteins
Biology
Mice
In vivo
Internal medicine
Cyclins
medicine
Vitamin D and neurology
Tumor Cells
Cultured
Animals
Cell Nucleus
Mice
Inbred C3H
Cell growth
Tumor Suppressor Proteins
Cell Cycle
Intracellular Signaling Peptides and Proteins
Proteins
medicine.disease
Blotting
Northern
Genes
p53
Head and neck squamous-cell carcinoma
Immunohistochemistry
Precipitin Tests
Endocrinology
Oncology
Epidermoid carcinoma
Head and Neck Neoplasms
Cancer cell
Carcinoma
Squamous Cell
RNA
Microtubule-Associated Proteins
Cell Division
Cyclin-Dependent Kinase Inhibitor p27
Neoplasm Transplantation
medicine.drug
DNA Damage
Zdroj: Journal of the National Cancer Institute. 93(10)
ISSN: 0027-8874
Popis: BACKGROUND 1alpha,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] and its analogues inhibit growth of various types of cancer cells. Although the therapeutic potential of 1,25(OH)(2)D(3) is limited by its tendency to induce hypercalcemia, analogues such as EB1089 are potent inhibitors of cell growth and exhibit reduced calcemic effects. We analyzed the antiproliferative and calcemic effects of EB1089 in tissue culture and animal models of head and neck squamous cell carcinoma (SCC) to investigate its potential as a chemotherapeutic/chemopreventive agent. METHODS The effects of 1,25(OH)(2)D(3) and EB1089 on cell growth and expression of p21(WAF1/CIP1) and p27(KIP1), which encode cyclin-dependent kinase inhibitors, and a novel target, gadd45alpha, a growth-arrest and DNA-damage gene, were monitored in cultured murine AT-84 SCC cells. The effects of these agents on AT-84 cell growth in vitro and on growth of AT-84 tumors in syngeneic C3H mice were monitored; treatment started at the time of tumor implantation (early tumor model) or after 12 days (late tumor model). Weight and serum calcium levels were also monitored in these animals. All P values were two-sided. RESULTS Both 1,25(OH)(2)D(3) and EB1089 arrested proliferation of AT-84 cells in G(0)/G(1) phase, inhibited p21(WAF1/CIP1) expression, and induced expression of p27(KIP1) protein. 1,25(OH)(2)D(3) also enhanced the expression of gadd45alpha, apparently by a p53-independent mechanism. There was a statistically significant decrease in tumor growth for 1,25(OH)(2)D(3)-treated mice (P
Databáze: OpenAIRE
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