Antiproliferative effects of the histone deacetylase inhibitor FR901228 on small-cell lung cancer lines and drug-resistant sublines
| Autor: | Junji Tsurutani, Yoichi Nakamura, Katsumi Nakatomi, Hiroshi Soda, Mikio Oka, Mitsuhiro Suenaga, Ken Shiozawa, Yasuaki Y amada, Shigeru Kohno, Shimeru Kamihira, Seiji Doi |
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| Rok vydání: | 2003 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cancer Research Telomerase Lung Neoplasms Time Factors medicine.drug_class Apoptosis Biology Peptides Cyclic Retinoblastoma Protein chemistry.chemical_compound Cyclins Depsipeptides medicine Tumor Cells Cultured Humans Telomerase reverse transcriptase RNA Messenger Carcinoma Small Cell neoplasms Cell growth Histone deacetylase inhibitor Cell Cycle Sodium butyrate Drug Resistance Multiple Anti-Bacterial Agents DNA-Binding Proteins Histone Deacetylase Inhibitors Trichostatin A Oncology chemistry Cell culture Drug Resistance Neoplasm Immunology Cancer research Histone deacetylase Cell Division medicine.drug |
| Zdroj: | International journal of cancer. 104(2) |
| ISSN: | 0020-7136 |
| Popis: | FR901228 is a novel histone deacetylase (HDAC) inhibitor, and its antiproliferative effects on non-small cell lung cancer cells have been shown in vitro. However, there have been no reports concerning the effects on small-cell lung cancer (SCLC). We have recently demonstrated that the HDAC inhibitors trichostatin A and sodium butyrate inhibit expression of the catalytic subunit of telomerase (hTERT) mRNA and telomerase activity in prostate cancer cells. The present study was designed to evaluate the effects of FR901228 on proliferation and telomerase activity in SCLC cells in vitro. FR901228 at 5 to 10 nM increased the fraction of cells in the G(2)/M and sub-G(1) phases of the cell-cycle, and inhibited the growth of H69, H526 and H82 cell lines. The expression of hTERT mRNA was inhibited 6 hr after treatment, prior to obvious inhibition of cell growth or cell-cycle distribution shifts. The inhibition of hTERT mRNA expression and telomerase activity was not a consequence of cell-growth arrest or apoptosis. Cycloheximide blocked the suppression of hTERT mRNA induced by FR901228, and the inhibition of hTERT mRNA by FR901228 required newly synthesized proteins. FR901228 also effectively inhibited growth of etoposide-resistant UMCC-1/VP-16, irinotecan-resistant PC-6/SN2-5H and cisplatin-resistant H526/CDDP cells having decreased expression of hTERT mRNA and telomerase activity, as well as their parental cells. This implies that SCLC resistant to these key drugs are not cross-resistant to FR901228. The present study suggests that FR901228 may be a promising drug for chemotherapy of cancers including SCLC, even for refractory or relapsing tumors after conventional chemotherapy. |
| Databáze: | OpenAIRE |
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