Abstract LB-420: Chinese medicinal herb Oldenlandia diffusa inhibits Azoxymethane-induced aberrant crypt foci in C57BL/6 mice and modulates apoptosis in mice and in human colon cancer cells

Abstract

Abstract Oldenlandia diffusa (OD) has been used in traditional Chinese medicine to treat appendicitis, lung, liver, and rectal cancers. Our early studies showed that OD contained phytochemicals that inhibited mutagenesis, DNA binding, and metabolism of aflatoxin B1 (AFB1) and benzo[a]pyrene bioactivated by Arcoclor 1254-induced rat S9. It also inhibited the mutagenicity of AFB1 bioactivated by either non-induced or DXM-induced hepatic S9, suggesting its effect via an inhibition of CYP3-mediated metabolism of [3H]AFB1. Recent oral feeding data demonstrated that OD could delay prostate tumor development in TRAMP mice. Complementary in vitro data indicated that OD induced Caspase 3, 8, and 9 via up-regulating the apoptotic pathway in human (LNCaP) prostate cancer cells. In this study, C57BL/6 mice (N = 30) of 9 wk old were randomized into three groups (N = 10). Mice of the positive control and experimental groups were injected with AOM (5 mg/kg body wt) at the beginning and second wk of the 8-wk duration while the negative control group received no injection. Animals in the experimental group received daily oral feedings of 24 mg OD since day 1 while mice in the other two groups were given a sterilized water placebo. OD feeding significantly reduced the number of AOM-induced ACF in the proximal colon (25 mm) compared with the water-fed positive control AOM-induced group (22.8 ± 1.75 < 32.1 ± 9.86; P < 0.009). The negative non-induced group had minimal ACF (2.0 ± 1.56) compared to the experimental and positive control groups (P < 0.001; P < 0.001 respectively). The potency index of the herb was calculated as 1.41. Percent inhibition of AOM-induced ACF formation of 29.1% was obtained with OD treatment. Mice in all three groups had gained weight (% increase) in the course of the experiment (experimental, 14.8 ± 8.28 < negative control, 15.6 ± 3.53 < positive control, 39.4 ± 19.54). Histological (H&E) slides of mouse colons with AOM+OD treatment revealed higher apoptotic index (AI) than positive control (AOM only) (1.8 > 0.6) and lower mitotic index (MI) than control (1 < 2.8). Immunohistological staining colon sections of OD-fed animal also showed significant inhibition of mutant p53 as compared to the positive control (3.6 ± 1.34; P < 0.032). Caspase 3 induction was detected in human (CLL) colon cancer cells treated with OD (1 mg / mL) in chamber slides, using a specific carboxyfluorecein (FAM) labeled peptide fluoromethyl ketone (FMK) caspase inhibitor (FAM-Peptide-FMK). Caspase 3 activation was also observed in OD treated colon tissues. These data suggest the inhibition effect of AOM-induced ACF by OD via apoptosis and its potential chemopreventive and treatment of colon cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-420.