Pro-apoptotic activity of ergosterol peroxide and (22E)-ergosta-7,22-dien-5alpha-hydroxy-3,6-dione in human prostate cancer cells.
With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on prostate cancer cells, we assayed the effect of ergosterol peroxide and (22E)-ergosta-7,22-dien-5alpha-hydroxy-3,6-dione, a semisynthetic compound, against androgen-sensitive (LNCaP) and androgen-insensitive (DU-145) human prostate cancer cells. Our results indicate that after 72h of incubation, ergosterol peroxide and (22E)-ergosta-7,22-dien-5alpha-hydroxy-3,6-dione at micromolar concentrations exhibited an inhibitory effect on LNCaP and DU-145 cell growth (MTT assay), but the semisynthetic compound was the most active. In addition, our results indicate that apoptotic cell demise is induced in LNCaP and DU-145 cells. In fact, a significant increase of caspase-3 activity, not correlated to LDH release, marker of membrane breakdown, was observed in both cell lines treated with ergosterol peroxide and the semisynthetic compound. With respect to genomic DNA damage, determined by COMET and TUNEL assays, the results obtained show a significant increase in DNA fragmentation when compared with the untreated control. In conclusion, the results obtained in this study, demonstrating that ergosterol peroxide and (22E)-ergosta-7,22-dien-5alpha-hydroxy-3,6-dione attenuate the growth of prostate cells, at least in part, triggering an apoptotic process, permit to confirm the use of mushrooms as origin of compounds to be used as novel therapeutic agents for prostate cancer treatment, or as models for molecules more active and selective.
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Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, V.le A. Doria 6, 95125 Catania, Italy. ales0303@libero.it <ales0303@libero.it>
Cardile
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Piovano
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Caggia
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Espinoza
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Garbarino
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D020552:Comet Assay; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D020287:In Situ Nick-End Labeling; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; C549042:ergosta-7,22-dien-5-hydroxy-3,6-dione; D045022:Lactate Dehydrogenases; D053148:Caspase 3; C036071:ergosterol-5,8-peroxide; D004875:Ergosterol