METHODS: 45 rats at 6 weeks of age, were randomly assigned to nine groups with 5 rats in each group, both azoxymethane (AOM) and 5-Fluorouracil (5-FU) were given to rats according to the body weight. NDV virus strains (AF2240 and V4-UPM) doses were determined to rats according to CD50 resulted from MTT assay. After 8 doses of NDV strians and 5-FU, tissue sections preparations and histopathological study of rats' organs were done.
RESULTS: In this article morphological changes of rats' organs, especially in livers, after treatment with a colon carcinogen (azoxymethane) and Newcastle disease virus strains have been recorded. We observed liver damage caused by AOM evidenced by morphological changes and enzymatic elevation were protected by the oncolytic viruses sections. Also we found that combination treatment NDV with 5-FU had greater antitumor efficacy than treatment with NDV or 5-FU alone.
CONCLUSION: We noted morphological changes in liver and other rats' organs due to a chemical carcinogen and their protection by NDV AF2240 and NDV V4-UPM seems to be most protective.
METHODS: Mice were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μL) followed by, in subsequent week, repeated promotion (twice weekly; 22 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μL). Annonacin (85 nM) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application for 22 weeks. Upon termination, histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted to elucidate the potential mechanism of annonacin.
RESULTS: With comparison to the carcinogen control, Annonacin significantly increased the tumor latency period and reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, mTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis.
CONCLUSIONS: Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.
MATERIALS AND METHODS: Seventy-two male Sprague-Dawley rats were divided into 6 equal groups with 12 rats in each group. For cancer induction two intraperitoneal injections of azoxymethane (AOM) were given at 15 mg/kg bodyweight over a 2-weeks period. During the post initiation phase, two different concentrations of PA, 0.2% (w/v) and 0.5% (w/v) were administered in the diet.
RESULTS: Results of β-catenin, COX-2 expressions and cell proliferation of Ki-67 showed a significant contribution in colonic cancer progression. For β-catenin and COX-2 expression, there was a significant difference between groups at p<0.05. With Ki-67, there was a statistically significant lowering the proliferating index as compared to AOM alone (p<0.05). A significant positive correlation (p=0.01) was noted between COX-2 expression and proliferation. Total β-catenin also demonstrated a significant positive linear relationship with total COX-2 (p=0.044).
CONCLUSIONS: This study indicated potential value of PA extracted from rice bran in reducing colonic cancer risk in rats.