Antiproliferative and Apoptotic Activities of Ketonucleosides and Keto-C-Glycosides against Non-Small-Cell Lung Cancer Cells with Intrinsic Drug Resistance
| Autor: | Jesse Paterson, Kostas Antonakis, Clara Uriel, Jean Herscovici, Moulay A. Alaoui-Jamali, Marie-Jose Egron |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Lung Neoplasms
Cell Survival Antineoplastic Agents Apoptosis Biology Cell Line In vivo Carcinoma Non-Small-Cell Lung Tumor Cells Cultured medicine Humans Cytotoxic T cell Pharmacology (medical) Glycosides Mechanisms of Action: Physiological Effects Etoposide Pharmacology Cisplatin Cancer Nucleosides Biological activity Genes p53 medicine.disease Infectious Diseases Drug Resistance Neoplasm Cell culture Immunology Cancer research Cell Division medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 42:779-784 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.42.4.779 |
| Popis: | We compared the biological activity of a new group of keto-C-glycosides to that of a narrow spectrum of unsaturated ketonucleosides in a panel of non-small-cell lung cancer (NSCLC) cells with various levels of intrinsic resistance to standard chemotherapy drugs. Unlike cisplatin, etoposide, adriamycin, or taxol, for which a significant difference in the cytotoxic effect was observed between sensitive cell lines (H460, H125, and MGH4) and drug-resistant cell lines (H661, MGH7, and FADU), nucleoside analogs were equally cytotoxic in NSCLC cell lines, with compound 92 being 10-fold more active than compound 43, 44, 81, or 161, while compound 3 was the least active. Apoptotic measurements with flow cytometric analysis of terminal uridine deoxynucleotide nick end-labeled cells revealed that the cytotoxic activity of these nucleosides correlated with their potency to induce apoptosis. Compound 92 triggered death in cells with wild-type p53, mutated p53, or p53 gene deletion. Our findings suggest that keto-C-glycosides may be promising alternative anticancer agents which merit further studies in in vivo cancer models refractory to standard chemotherapy drugs. |
| Databáze: | OpenAIRE |
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