No abstract

The protective role of Luteolin (LUT) against Azoxymethane (AOM)-induced mouse colon carcinogenesis has been documented earlier. The aim of this study is to investigate on the mechanism of chemopreventive action exhibited by LUT employing AOM-induced colon carcinogenesis in mice as an experimental model. LUT inhibited AOM-induced colon tumorigenesis by decreasing tumor incidence and size. LUT reduced the cell proliferation by decreasing the number of Argyrophillic nucleolar organizer region (AgNOR)/nucleus and Proliferating Cell Nuclear Antigen (PCNA) index. It was known that β-catenin is a key effector in Wingless and Int (Wnt) signaling pathway and 90% of colon tumors arise from mutations in this pathway. In this study, we show evidence that LUT inhibited colon carcinogenesis by decreasing AOM-induced cell proliferation through the involvement of β-catenin, Glycogen synthase kinase (GSK)-3β and cyclin D1, the key components in Wnt signaling pathway. In conclusion, the protective effect of LUT could be attributed to inhibition of AOM-induced cellular proliferation probably through the involvement of β-catenin, GSK-3β and cyclin D1.

Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of human cancer. Diallyl sulfide (DAS), an organosulfur component of garlic has been known for its chemopreventive activities against various cancers and also in recent years, numerous investigations have shown that sulfur-containing compounds induce apoptosis in multiple cell lines and experimental animals. Thus the present study was focused to elucidate the anticancerous effect and the mode of action of DAS against Colo 320 DM colon cancer cells. DAS induced apoptosis in Colo 320 DM cells was revealed by flow cytometer analysis and phosphatidyl serine exposure. DAS also promoted cell cycle arrest substantially at G2/M phase in Colo 320 DM cells. The production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with DAS. The activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were decreased upon DAS treatment, which shows the antiproliferative and the cytotoxic effects, respectively. The expression of NF-kappaB was upregulated in DAS treated cells, compared to normal cells. Further, DAS promoted the expression of caspase-3 and suppression of Extracellular Regulatory Kinase-2 (ERK-2) activity in Colo 320 DM cells that was determined by Western blot analysis. In conclusion, DAS increased the production of ROS, caused cell cycle arrest, decreased cell proliferation and induced apoptosis in Colo 320 DM cells. Thus, this study put forward DAS as a drug that can possibly be used to treat cancers.

Colon cancer is one of the major causes of cancer mortality worldwide. Several carotenoids with antioxidant properties are reported for their chemopreventive nature. In this study, we have evaluated the chemopreventive efficacy of astaxanthin on lipid peroxidation, antioxidant status, total number of aberrant crypt foci (ACF), and cell proliferation in 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis using a rat model. DMH was induced subcutaneously at a dosage of 40 mg/kg body weight, twice a week for 2 weeks. Astaxanthin was administered before and after the DMH induction, orally at a concentration of 15 mg/kg body weight throughout the experimental period. At the end of 16 weeks, pre-treatment with astaxanthin markedly reduced the degree of histological lesions, ACF development and also lowered the number of argyrophilic nucleolar organizer regions. Our results also showed the decreased levels of colon enzymic and non-enzymic antioxidants and increased levels of lipid peroxidation marker levels in DMH-induced rats, which were significantly reversed on astaxanthin administration. In conclusion, the results of this study suggest that astaxanthin has an affirmative and beneficial effect against chemically induced colonic pre-neoplastic progression in rats induced by DMH.