title: Diallyl trisulfide is more cytotoxic to prostate cancer cells PC-3 than to noncancerous epithelial cell line PNT1A: a possible role of p66Shc signaling axis.
abstract: Diallyl trisulfide (DATS) is an organosulfur compound isolated from garlic, and has been shown to have anticancer activity both in vitro and in vivo. The aim of this study was to compare cytotoxic effects of DATS on prostate cancer cells PC-3 and noncancerous human prostate epithelial cells PNT1A. PC-3 prostate cancer and noncancerous human prostate epithelial cells PNT1A were used in the study. We observed that PNT1A cells had higher resistance to DATS-induced cell death than PC-3 cells. Investigating signaling pathways involved in the cell death we observed that p66Shc phosphorylation at serine 36 and extracellular signal-regulated kinase 1/2 activation induced by DATS, were significantly attenuated in PNT1A cells as compared to PC-3 cells. Moreover, DATS-induced Akt inactivation was also significantly reduced in PNT1A cells. In addition to that, DATS-induced reactive oxygen species generation was nearly completely abolished in PNT1A cells. Interestingly, DATS induced only slight decrease in the level of ferritin H, whereas ferritin L was elevated. These data suggest that cytotoxicity of DATS toward PNT1A cells is strongly reduced as opposed to PC-3 cancer cells, which corresponds to the lower activation of prodeath signaling pathway mediated by the adaptor protein p66Shc in the noncancerous PNT1A cells.
authors.affiliation: Department of Bioenergetics and Physiology of Exercise, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Andzelika
authors.initials: A
authors.lastname: Borkowska
authors.forename: Narcyz
authors.initials: N
authors.lastname: Knap
authors.forename: Jędrzej
authors.initials: J
authors.lastname: Antosiewicz
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D005737:Garlic / Q000737:chemistry; D006801:Humans; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013440:Sulfides; C042577:diallyl trisulfide; D005293:Ferritins; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3