kava and Colonic-Neoplasms

Chalcones and their derivatives belong to the flavonoid family. They have been extensively studied for their anticancer properties and some have been approved for clinical use. In this study, the in vivo anti-tumor activity of flavokawain C (FKC), a naturally occurring chalcone found in Kava (Piper methysticum Forst) was evaluated in HCT 116 cells (colon carcinoma). We also attempted to identify potential biomarkers and/or molecular targets in serum with applicability in predicting treatment outcome. The anti-tumor effects and toxicity of FKC were assessed using the xenograft nude mice model. Cisplatin was used as positive control. The anti-proliferative and apoptotic activities were then evaluated in tumor tissues treated with FKC. Furthermore, two-dimensional electrophoresis (2-DE) followed by protein identification using MALDI-TOF/TOF-MS/MS was performed to compare the serum proteome profiles between healthy nude mice and nude mice bearing HCT 116 tumor treated with vehicle solution and FKC, respectively. Our results showed that FKC treatment significantly inhibited HCT 116 tumor growth. In vivo toxicity studies showed that administration of FKC did not cause damage to major organs and had no significant effect on body weight. FKC was found to induce apoptosis in tumor, and this was associated with increased expression of cleaved caspase-3 and decreased expression of Ki67 in tumor tissues. Our proteomic analysis identified five proteins that changed in abundance - Ig mu chain C region (secreted form), GRP78, hemopexin, kininogen-1 and apolipoprotein E. Overall, our findings demonstrated the potential of FKC as an anti-cancer agent for the treatment of colon carcinoma.

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Body Weight; Caspase 3; Cell Proliferation; Chalcones; Cisplatin; Colonic Neoplasms; Endoplasmic Reticulum Chaperone BiP; Female; HCT116 Cells; Humans; Kava; Mice; Mice, Inbred BALB C; Mice, Nude; Proteomics; Xenograft Model Antitumor Assays

Epidemiological studies indicate there is low incidence of colon cancer in the South Pacific islands, including Fiji, West Samoa, and Vanuatu. Cancer incidence has been shown to be inversely associated with kava (Piper methysticum G. Forst.) ingestion. Hypothesis/Purpose: Kava prepared traditionally will inhibit the growth of human cancer cells. This investigation entails preparation and analysis of kava extracts and study of the growth inhibitory activity of the extracts, alone and combined with hibiscus.. We will prepare kava as in Micronesia - as a water extract, high in particulate content, alone or combined with sea hibiscus (Hibiscus tiliaceus L.) - and examine the components and growth inhibitory activity.. We obtained ground kava prepared in the traditional way from lateral roots and sea hibiscus mucilage and sap from different sources in Micronesia, and prepared water extracts (unfiltered, as well as filtered, since in traditional use the kava beverage contains a high particulate content) and partitions. We used the MTT assay to determine the growth inhibitory activity of the preparations on colon and breast cancer cells and nonmalignant intestinal epithelial cells. LC-MS analysis was used to examine the components of the kava and sea hibiscus extracts and partitions.. Traditional preparations of kava inhibit the growth of breast and colon cancer cells. Among the kava preparations, the order of decreasing activity was Fiji(2), Fiji(1), Hawaii; the unfiltered preparations from Fiji were more active than the filtered. Phytochemical analysis indicated that filtering reduced most kavalactone and chalcone content. For example, for Fiji(2), the ratio of dihydromethysticin in filtered/unfiltered kava was 0.01. Thus, for the extracts from Fiji, growth inhibitory activity correlates with the content of these compounds. Unfiltered and filtered kava from Fiji(1) were more active on malignant than nonmalignant intestinal epithelial cells. Since kava is prepared in Micronesia by squeezing the extract through sea hibiscus bark, we assayed the growth inhibitory activity of combinations of kava and sea hibiscus sap and found that sea hibiscus enhanced the growth inhibitory effect of kava.. Our results show that traditional kava, alone or combined with sea hibiscus, displays activity against human cancer cells and indicate it will be worthwhile to develop and further analyze these preparations to prevent and treat colon and other cancers. Our findings suggest it is important to examine the activity of plants in the form that people consume them.

Topics: Colonic Neoplasms; Fiji; Hibiscus; Humans; Kava; Mass Spectrometry; Phytotherapy; Plant Extracts; Plant Growth Regulators; Plant Roots; Pyrones; Samoa; Tumor Cells, Cultured; Vanuatu

Epidemiological studies suggest that kava reduces colon cancer risk. However, no experimental studies of the chemopreventive properties of kava toward colon cancer have been reported. Further, there are concerns regarding hepatotoxicity of kava. The goal of this study was to determine whether kava consumption reduces markers of colon cancer in an animal model and to study the safety of kava. An ethanolic extract and polar and nonpolar fractions of the kava extract were fed to rats for 12 days prior to, during, and after administration of dimethylhydrazine, a colon-specific carcinogen. After 14 wk, rats fed the nonpolar extract had a significant reduction in precancerous lesions [aberrant crypt (AC) foci (ACF)] as well as large (≥ 4 AC/ACF) sialomucin-only expressing foci, an indicator of greater tumorigenic potential, compared to the control group. Groups fed the ethanolic extract and polar kava fraction trended toward reductions in ACF and large sialomucin-only expressing foci. The combined kava groups had significantly fewer total AC, ACF, large ACF, and large sialomucin-only expressing foci compared to the control group. Histological examination found no hepatic lesions in animals consuming the kava diets, suggesting that kava is safe to consume. Our results support that kava may reduce colon cancer risk.

Topics: 1,2-Dimethylhydrazine; Animals; Anticarcinogenic Agents; Body Weight; Carcinogens; Colonic Neoplasms; Eating; Kava; Liver; Male; Organ Size; Plant Extracts; Plants, Medicinal; Precancerous Conditions; Rats; Rats, Wistar