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Pro-apoptotic activity of ergosterol peroxide and (22E)-ergosta-7,22-dien-5α-hydroxy-3,6-dione in human prostate cancer cells
Authors:A Russo  V Cardile  M Piovano  S Caggia  CL Espinoza  JA Garbarino
Institution:1. Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, V.le A. Doria 6, 95125 Catania, Italy;2. Department of Physiological Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy;3. Department of Chemistry, University T.F. Santa Maria, Casilla 110-V, Valparaiso, Chile;1. Department of Microbiology, College of Life Sciences, Nanjing Agricultural University, Key Laboratory of Microbiological Engineering of Agricultural Environment, Ministry of Agriculture, Nanjing 210095, Jiangsu, PR China;2. Jiangsu Alphay Bio-technology Co., Ltd./Key Laboratory of Edible Mushroom Processing, Ministry of Agriculture, Nantong 226009, Jiangsu, PR China;1. Servicio de Cardiología, Hospital Universitario Ramón y Cajal, Madrid, Spain;2. Servicio de Cardiología, Hospital Universitario La Paz, Madrid, Spain;1. Doctorado en Ciencias Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala s/n, Col. Industrial Ánimas, C.P. 91190 Xalapa, Veracruz, Mexico;2. Laboratorio de Alta Tecnología de Xalapa (LATEX), Calle Médicos 5, Col. Unidad del Bosque, C.P. 91010 Xalapa, Veracruz, Mexico;3. Instituto de Ciencias Básicas, Universidad Veracruzana, Av. Luis Castelazo Ayala s/n, Col. Industrial Ánimas, C.P. 91190 Xalapa, Veracruz, Mexico;1. State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Science, Kunming 650201, People’s Republic of China;2. Graduate School of Chinese Academy of Science, Beijing 100049, People’s Republic of China;3. College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, People’s Republic of China;1. Hainan Key Laboratory of Storage & Processing of Fruits and Vegetables, Agricultural Products Processing Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524001, China;2. Key Laboratory of Tropical Crop Products Processing of the Ministry of Agriculture and Rural Affairs, Zhanjiang 524001, China;3. College of Tea (Pu’er), West Yunnan University of Applied Sciences, Pu’er 665000, China;4. R&D Department, SCG Cell Therapy Pte Ltd., Shanghai 200000, China;5. Key Laboratory for Postharvest Physiology and Technology of Tropical Horticultural Products of Hainan Province, South Subtropical Crops Research Institute, Chinese Academy of Tropical Agricultural Sciences, Zhanjiang 524091, China;6. College of Food Science and Engineering, Lingnan Normal University, Zhanjiang 524037, China;7. College of Food Science, South China Agricultural University, Guangzhou 510640, China;8. Nine Max Instrument Co., Nanjing 210000, China
Abstract: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-5α-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 72 h of incubation, ergosterol peroxide and (22E)-ergosta-7,22-dien-5α-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-5α-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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