Plantago major (PM), commonly known as common plantain, is a temperate perennial herb. Traditionally, its seeds and leaves have been ingested or applied externally to treat inflammation and infection. Studies showed PM possesses inhibitory effects towards a variety of tumors and cancer cell lines, including mice Ehrlich ascites carcinoma and breast adenocarcinoma, gastric, leukaemia, ovary, melanoma, and renal human cell lines. While PM has been shown to exhibit selective cytotoxic activity against cancer cells, its quantitative potential as a chemopreventive agent on colon cancer has yet to be elucidated. In this study, C57BL/6 mice (N = 30) of 9 wk old were randomized into three groups (N = 10). Positive and experimental mice groups were injected with Azoxymethane (AOM; 5 mg/kg body weight) at the onset and second wk of the 8-wk duration of the in vivo study while the negative group received no injection. The mice in the experimental group were given daily oral feedings of 20 mg/ml of PM from the onset of the study while the negative and positive control groups were given a sterilized water placebo. All groups were sacrificed after 8 wks and 25 mm cuts of the proximal colon were analyzed for aberrant crypt foci (ACF). PM feeding significantly reduced the number of AOM-induced ACF in the proximal colon compared to the water-fed positive control AOM-induced group (7.02 ± 2.61 < 32.1 ± 9.86; P < 0.0003). The negative control, water placebo group had minimal ACF (2.0 ± 1.56) compared to the experimental and positive control groups. The potency index of the herb was calculated as 4.57. Percent inhibition of AOM-induced ACF formation of 78.1% was obtained with the PM treatment. On average, all three groups gained weight (calculated as % increase) through the course of the experiment (experimental, 6.93 < negative control 15.6 < positive control 39.4). Histological (H&E) slides of the proximal colon displayed a significantly higher apoptotic index than the positive control (AOM only) (2.0 > 0.6) and a lower mitotic index (MI) than control (1.5 < 2.8). Caspase 3 induction was identified in human colon cancer cells (COLO-205) treated with PM (5mg/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 immunofluorescent slides of PM treated proximal colon tissues. Through inhibition of AOM-induced ACF via apoptosis, our data suggests PM to be a prospective chemopreventive and potential therapeutic agent for colon cancer. Citation Information: Cancer Prev Res 2010;3(12 Suppl):A50.

Taraxacum officinale (TO), the common dandelion, has been used traditionally as a diuretic and as a treatment for jaundice and other liver disorders. Recent studies have substantiated its diuretic effect; in addition, it exhibits considerable antimicrobial, anti-inflammatory, antioxidant, hypolipidemic, and anti-breast and anti-prostate cancer-cell properties. In this study, the effects of TO as a chemopreventive agent of early-stage colon cancer development were evaluated. In the in vivo investigation, C57BL/6 mice between 6–10 wk old were randomized into negative control (N = 10), positive control (N = 10), and experimental (N = 10) groups. Aberrant crypt foci (ACF), putative precursors of colon cancer, were induced in positive control and experimental mice by intraperitoneal injection of azoxymethane (AOM; 5 mg/kg body mass) at the beginning of the first and second weeks, while the negative control mice received none. The experimental group was daily fed TO extract (1 mL/mouse; 84.22 mg/mL) by gavage throughout the duration of the 8-wk study while the control groups received a sterilized-water placebo. Mice in all three groups were sacrificed at the end of the 8-wk period and 25 mm of the proximal colon were resected and analyzed for ACF development after staining with methylene blue. Histological preparations of the proximal colon samples were used to determine apoptotic index, mitotic index, and caspase induction. Oral TO administration significantly reduced the number of AOM-induced ACF in the proximal colon in the experimental group in comparison to the positive control group (10.67 ± 3.75 < 32.10 ± 9.86; P < 0.00016), which indicates a 68.9 % inhibition of ACF formation by TO and a potency index of 3.01. The mice in all three groups experienced weight gain (negative: 7.0% < positive: 7.5% < experimental: 8.1%). Colon samples from the experimental group revealed a higher apoptotic index (AI) (1.34 > 0.60; P < 0.0002) and a lower mitotic index (MI) (1.13 < 2.80; P < 0.25) than the positive control group (AOM only). Caspase 3 and 9 induction was detected in human colorectal carcinoma HCT-116 cells treated with TO (.05 mg/mL) in chamber slides, using a specific carboxyfluorecein (FAM) labeled peptide fluoromethyl ketone (FMK) caspase inhibitor (FAM-peptide-FMK). Caspase 3 and 9 activation was also observed in TO-treated mouse colon tissues using the same caspase inhibitor. The data suggests that TO possesses potential chemopreventive effects on colon cancer development through the inhibition of AOM-induced ACF formation via C3/C9-regulated apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-21. doi:10.1158/1538-7445.AM2011-LB-21