Thai Rat-Tailed Radish Prevents Hepatocarcinogenesis in Rats by Blocking Mutagenicity, Inducing Hepatic Phase II Enzyme, and Decreasing Hepatic Pro-Inflammatory Cytokine Gene Expression

SIMPLE SUMMARY: Our previous studies have reported the anticancer activity of Raphanus sativus L. var. caudatus Alef (RS) in many cancer cells, but only in vitro. The anticancer effects of RS were, therefore, investigated in rats with early-stage liver cancer. RS effectively reduced the overexpression of GST-P positive foci and apoptotic cells in the rats injected with DEN (a carcinogen) during the development of early-stage of cancer. The major finding from this study highlights the chemopreventive activity of RS extract given orally in the initial stage of hepatocarcinogenesis in vivo by (1) inhibiting carcinogenic activities, (2) increasing phase II metabolism, and by (3) lower inflammation. The attributed compounds to these activities could be polyphenols and isothiocyanates, mainly sulforaphene. The results confirm sufficient oral bioavailability, with no detected toxicity, and thus support the use of RS as a health-promoting plant and its possible further study and use in humans. ABSTRACT: Raphanus sativus L. var. caudatus Alef (RS) is an indigenous Thai plant with nutritional and medicinal values such as anticancer activity, but only in vitro. The chemopreventive effects of RS were, therefore, investigated in the initial stage of hepatocarcinogenesis in rats. Diethylnitrosamine (DEN), a carcinogen, was intraperitoneally injected into rats to induce liver cancer. Along with the DEN injection, either aqueous (RS-H(2)O) or dichloromethane (RS-DCM) extract was administered orally. Immunohistochemistry was used to detect glutathione S-transferase placental (GST-P) positive foci and apoptotic cells in rat livers as indicators of initial-stage carcinogenesis. The underlying mechanisms of chemoprevention were investigated with (a) antimutagenic activity, (b) hepatic phase II enzyme induction, and (c) hepatic pro-inflammatory cytokine gene expression. The results showed that RS-DCM was more potent than RS-H(2)O in decreasing GST-P positive foci and apoptotic cells induced by DEN. The mechanisms of RS-DCM (phenolics and sulforaphene contents) against liver carcinogenesis (1) block the activity of carcinogens; (2) elevate phase II detoxifying enzymes; and (3) suppress the pro-inflammatory gene expression. RS-H(2)O (phenolics contents), in contrast, only decreases pro-inflammatory gene expression. In conclusion, the RS extract consisting of phenolics and isothiocyanates exerted significant chemopreventive activity against DEN-induced liver carcinogenesis.