The neuro-steroid, 3β androstene 17α diol exhibits potent cytotoxic effects on human malignant glioma and lymphoma cells through different programmed cell death pathways
| Autor: | M R Graf, Wentao Jia, R M Loria |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Programmed cell death Lymphoma Cell Survival Blotting Western Apoptosis DNA Fragmentation Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glioma Cell Line Tumor Phagosomes medicine In Situ Nick-End Labeling Cytotoxic T cell Humans programmed cell death 030304 developmental biology Cell Proliferation 0303 health sciences androstene neuro-steroids U937 cell Dose-Response Relationship Drug Molecular Structure Cell growth Caspase 3 Acridine orange glioblastoma malignant glioma U937 Cells medicine.disease Flow Cytometry Androstane-3 17-diol 3. Good health Oncology chemistry Cell culture 030220 oncology & carcinogenesis Cancer research Poly(ADP-ribose) Polymerases Translational Therapeutics Signal Transduction |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | The neuro-steroids 3beta-androstene-17alpha-diol (17alpha-AED), 3beta-androstene-17beta-diol (17beta-AED), 3beta-androstene-7alpha,-17beta-triol (7alpha-AET) and 3beta-androstene-7beta,-17beta-triol (7beta-AET) are metabolites of dehydroepiandrosterone and are produced in neuro-ectodermal tissue. Both epimers of androstenediols (17alpha-AED and 17beta-AED) and androstenetriols (7alpha-AET and 7beta-AET) have markedly different biological functions of their chemical analogue. We investigated the cytotoxic activity of these neuro-steroids on human T98G and U251MG glioblastoma and U937 lymphoma cells. Proliferation studies showed that 17alpha-AED is the most potent inhibitor, with an IC(50) approximately 15 microM. For T98G glioma, 90% inhibition was achieved with 25 muM of 17alpha-AED. Other neuro-steroids tested only marginally suppressed cell proliferation. Reduced cell adherence and viability could be detected after 18 h of 17alpha-AED exposure. Treatment with 17alpha-AED induced a significant level of apoptosis in U937 lymphoma cells, but not in the glioma cells. Cytopathology of 17alpha-AED-treated T98G cells revealed the presence of multiple cytoplasmic vacuoles. Acridine orange staining demonstrated the formation of acidic vesicular organelles in 17alpha-AED-treated T98G and U251MG, which was inhibited by bafilomycin A1. These findings indicate that 17alpha-AED bears the most potent cytotoxic activity of the neuro-steroids tested, and the effectiveness may depend on the number of hydroxyls and their position on the androstene molecule. These cytotoxic effects may utilize a non-apoptotic pathway in malignant glioma cells. |
| Databáze: | OpenAIRE |
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