[50]). The major risk factors for hepatic cancer include chronic infection with hepatitis B and C (accounting for 54% and 31% of cases worldwide respectively), the consumption of food grains contaminated with mycotoxins (produced by fungi during storage in tropical or sub-tropical
climatic www.selleckchem.com/products/AZD8055.html countries) and last, but not the least, heavy alcohol consumption [1], [2] and [3]. Hepatocarcinogenesis involves initial genotoxic insult (initiation), clonal expansion from premalignant to malignant lesions (promotion) and finally tumor progression by means of further clonal expansion [4]. To date, surgery remains the best choice of treatment that could prolong HCC patients’ survival. However, poor prognosis at times after surgery along with side effects of various chemotherapeutic drugs are also being seen as causes of relapse [5]. In addition
to surgery, chemoprevention is another key approach to control HCC, where one or more nontoxic, naturally occurring or synthetic agents are administrated to prevent, improve or reverse the occurrence of disease substantially. Thus, chemopreventive intervention may serve as a feasible alternative strategy for prevention of liver tumorigenesis. In recent years, considerable efforts have been made to search naturally occurring substances for the intervention NVP-BKM120 in vivo of carcinogenesis [6] and [7]. Nexrutine® (NX), a commercially available herbal extract from Phellodendronamurense, widely used for the treatment of inflammation, gastroenteritis, abdominal pain and diarrhea, has shown to exhibit minimal toxicity to normal tissues [8]. Active components of NX are isoquinoline alkaloids, phenolic compounds and flavone glycosides. A recent study revealed that NX inhibited the proliferation of
L-gulonolactone oxidase prostate and lung cancer cells through the modulation of Akt and CREB-mediated signaling pathways, and that its anti-proliferative effects are comparable to that of berberine, a well-known chemopreventive agent [9], [10] and [11]. Other findings also established NX to be effective against early-stage prostate tumor development as well as tumor progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model [8] and [12]. In addition, recently our group showed that NX inhibited the promotion of skin tumorigenesis in the two-stage mouse skin tumorigenesis model [13]. Although NX has proven to be a potent anti-cancer agent for prostate, skin and lung cancer, no study so far has reported the anti-tumor effects of NX on liver cancer. Therefore, in this study, anti-inflammatory and anti-tumor promoting potential of NX was demonstrated in partially modified Solt-Farber rat liver tumorigenesis model.