Sulforaphane, a cruciferous vegetable-derived isothiocyanate, inhibits protein synthesis in human prostate cancer cells.
Sulforaphane (SFN) is a compound derived from cruciferous plants. Its anticancer properties have been demonstrated both, in cancer cell lines as well as tumors in animal models. It has been shown that SFN inhibits cell proliferation, induces apoptosis, autophagy, and sensitizes cancer cells to therapies. As induction of catabolic processes is often related to perturbation in protein synthesis we aimed to investigate the impact of SFN on this process in PC-3 human prostate cancer cells. In the present study we show that SFN inhibits protein synthesis in PC-3 cells in a dose- and time-dependent manner which is accompanied by a decreased phosphorylation of mTOR substrates. Translation inhibition is independent of mitochondria-derived ROS as it is observed in PC-3 derivatives devoid of functional mitochondrial respiratory chain (Rho0 cells). Although SFN affects mitochondria and slightly decreases glycolysis, the ATP level is maintained on the level characteristic for control cells. Inhibition of protein synthesis might be a protective response of prostate cancer cells to save energy. However, translation inhibition contributes to the death of PC-3 cells due to decreased level of a short-lived protein, survivin. Overexpression of this anti-apoptotic factor protects PC-3 cells against SFN cytotoxicity. Protein synthesis inhibition by SFN is not restricted to prostate cancer cells as we observed similar effect in SKBR-3 breast cancer cell line.
Department of Molecular Biology, University of Gdansk, Gdansk, Poland.
Aleksandra
A
Wiczk
Dagmara
D
Hofman
Grażyna
G
Konopa
Anna
A
Herman-Antosiewicz
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D019607:Brassicaceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D017879:Isothiocyanates; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms; D014176:Protein Biosynthesis / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013454:Sulfoxides; D000077022:Survivin; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D013861:Thiocyanates / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D017879:Isothiocyanates; D010936:Plant Extracts; D011500:Protein Synthesis Inhibitors; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D000077022:Survivin; D013861:Thiocyanates; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1; C016766:sulforaphane; D020123:Sirolimus