RESUMO
There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is partly due to the organosulfur compounds in Allium vegetables and that these substances act through induction of phase II detoxification enzymes. Here, we hypothesized that alk(en)yl thiosulfates, sodium n-propyl thiosulfate (NPTS), and sodium 2-propenyl thiosulfate (2PTS), which were identified in onions and garlic, respectively, may induce phase II enzymes. Therefore, rat hepatoma cells (H4IIE) were cultured with 1 to 100 micromol/L of NPTS or 2PTS for 48 hours at 37 degrees C; and the activities and messenger RNA (mRNA) expression levels of phase II enzymes in H4IIE cells were investigated. The effects of diallyl trisulfide and tert-butylhydroquinone, known as phase II inducers, were also examined as positive controls and compared with the responses of NPTS and 2PTS. Quinone reductase (QR) activity and mRNA expression levels of QR and epoxide hydrolase 1 were significantly increased by 2PTS (P < .05-.005). In particular, QR activity was increased at a relatively low concentration of 2PTS (10 micromol/L). However, glutathione S-transferase activity and mRNA expression levels of glutathione S-transferase A5 and uridine diphosphate glucuronosyl transferase 1A1 were not changed by 2PTS. In contrast, NPTS did not affect the activities and mRNA expression levels of these phase II enzymes. These results show that 2PTS can induce phase II enzymes, and its inductive effect is comparable or superior to that of diallyl trisulfide and tert-butylhydroquinone.
Assuntos
Compostos Alílicos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/enzimologia , Alho/química , Neoplasias Hepáticas/enzimologia , Desintoxicação Metabólica Fase II , Extratos Vegetais/farmacologia , Ésteres do Ácido Sulfúrico/farmacologia , Compostos Alílicos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Indução Enzimática , Epóxido Hidrolases/genética , Epóxido Hidrolases/metabolismo , Glucuronosiltransferase/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Hidroquinonas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Cebolas/química , Fitoterapia , RNA Mensageiro/metabolismo , Ratos , Sulfetos/farmacologia , Ésteres do Ácido Sulfúrico/uso terapêutico , Tiossulfatos/farmacologiaRESUMO
Two alk(en)yl thiosulfates, sodium n-propyl thiosulfate (NPTS) and sodium 2-propenyl thiosulfate (2PTS), are natural constituents of onion and garlic, respectively, which were identified originally as causative agents of onion- and garlic-induced hemolytic anemia in dogs. As a continuation of our studies on the beneficial functions of NPTS and 2PTS, in the present study, we investigated the antitumor effects of these compounds. They were shown to inhibit the in vitro proliferation of three human tumorigenic cell lines, WiDr, 293 and HL-60, in a dose-dependent manner. Overall, NPTS seemed to have weak activity for inhibiting cell growth compared with 2PTS, though not in WiDr cells, which were sensitive to both compounds. NPTS and 2PTS caused oxidative damage to HL-60 cells and induced apoptosis. The extent of apoptosis was approximately proportional to that of the oxidative damage and also to that of the cytotoxicity caused by these compounds. These results suggest that the alk(en)yl thiosulfates have an antitumor effect through the induction of apoptosis initiated by oxidative stress.