xanthohumol and Colonic-Neoplasms

Xanthohumol (XN) is a prenylated flavonoid known for its antioxidant and anti-inflammatory effects and has been studied as an anti-cancer agent. In this study, we aimed at analysing the effect of XN on a primary colorectal adenocarcinoma cell line, HT29, on cell viability, inflammatory and antioxidant gene expression, and metabolism. For this purpose, cells were treated with 10 nM and 10 µM XN, and cell viability, H

Topics: Antioxidants; Colonic Neoplasms; Flavonoids; HT29 Cells; Humans; Hydrogen Peroxide; Inflammation; Propiophenones

Xanthohumol (XN) is a hop-derived prenylflavonoid and have been reported to exhibit anticancer properties in several types of cancer. It presents a great interest against colon cancer due to high exposure of this compound in this tissue. Metastatic SW620 cell line was treated with doses ranging from 0.001 to 10 µM of XN to assess their effects on cell viability and mitochondrial function. At low concentrations, XN had no effect on assays carried out, but high concentration of XN led to a decrease in cell viability. In addition, at 10 μM XN, it gave rise to an increase in ROS production accompanied by a decrease in OXPHOS complexes and sirtuin 1 protein expression levels. These results suggest that XN could act as a mitocan and impairs mitochondrial function.

Topics: Beer; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Flavonoids; Humans; Humulus; Mitochondria; Oxidative Phosphorylation; Propiophenones; Reactive Oxygen Species; Sirtuin 1

Topics: Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Cycle; Cell Proliferation; Colonic Neoplasms; Flavonoids; HCT116 Cells; Hep G2 Cells; HT29 Cells; Humans; Liver Neoplasms; Propiophenones

Xanthohumol (XN) is a hop derived prenylated flavonoid contained in beer. Earlier findings indicated that it has promising chemopreventive properties and protects cells against DNA damage by carcinogens via inhibition of their activation. Furthermore, it was found that XN inhibits DNA synthesis and proliferation of cancer cells in vitro, inactivates oxygen radicals and induces apoptosis. Since evidence for its chemoprotective properties is restricted to results from in vitro experiments, we monitored the impact of XN on the formation of amino-3-methyl-imidazo[4,5-f]quinoline (IQ)-induced preneoplastic foci in livers and colons of rats (9/group). Additionally, we studied its effects on IQ-induced DNA damage in colonocytes and hepatocytes in single cell gel electrophoresis assays and on the activities of a panel of drug metabolising enzymes. Consumption of the drinking water supplemented with XN (71 microg/kg b.w.) before and during carcinogen treatment led to a significant reduction of the number of GST-p+ foci in the liver by 50% and also to a decrease of the foci area by 44%. DNA migration was decreased significantly in both, colon mucosa and liver cells, but no alterations of the activities of different phases I and II enzymes were found in hepatic tissue. Our findings indicate that XN protects against DNA damage and cancer induced by the cooked food mutagen. Since the effects were observed with low doses of XN which are reached after consumption of brews with high XN levels, our findings may be relevant for humans.

Topics: Animals; Carcinogens; Colon; Colonic Neoplasms; DNA Damage; Flavonoids; Liver; Liver Neoplasms; Male; Precancerous Conditions; Propiophenones; Quinolines; Rats; Rats, Inbred F344

Xanthohumol (XN) is one of the major prenylflavonoids found in hop cones (Humulus lupulus L.). In this study, we investigated the cell growth inhibitory potential of XN on cultured human colon cancer cells. Cell proliferation was measured by sulforhodamine B staining. Poly(ADP-ribose)polymerase (PARP) cleavage, activation of caspases-3, -7, -8, and -9, and Bcl-2 family protein expression were detected by Western blot analyses. XN significantly reduced proliferation of the HCT 116-derived colon cancer cell line 40--16. Half-maximal inhibitory concentrations decreased from 4.1 microM after 24 h treatment to 3.6 and 2.6 microM after 48 and 72 h incubation, respectively. Treatment with 15 microM XN for 48 h and with 5 microM for 72 h led to the detection of the cleaved 89 kDa fragment of 116 kDa PARP as an indication of apoptosis induction. Concomitantly, we observed activation and cleavage of the effector caspases-3 and -7, induced by activation of the initiator caspases -8 and -9. Expression of anti-apoptotic Bcl-2 was down regulated when the cells were treated with XN for 48--72 h. We conclude that induction of apoptosis by downregulation of Bcl-2 and activation of the caspase cascade may contribute to the chemopreventive or therapeutic potential of XN.

Topics: Apoptosis; Caspase 3; Caspase 7; Caspase 8; Caspase 9; Caspases; Cell Division; Cell Line, Tumor; Colonic Neoplasms; Enzyme Activation; Flavonoids; Humans; Humulus; Mitochondria; Poly(ADP-ribose) Polymerases; Propiophenones; Proto-Oncogene Proteins c-bcl-2