• Journal of Oral Medicine and Pain
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• v.32 no.3
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• pp.251-261
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• 2007

Bile acids and synthetic its derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. Previous studies have been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis inducing activity on various cancer cells in vitro. It wasn't discovered those materials have apoptosis induced effects on YD9 human oral squamous carcinoma cells. The present study was done to examine the synthetic bile acid derivatives(HS-1199, HS-1200) induced apoptosis on YD9 cells and such these apoptosis events. We administered them in culture to YD9 cells. Tested YD9 cells showed several lines of apoptotic manifestation such as activation of caspase-3, degradation of DFF, production of poly (ADP-ribose) polymerase(PARP) cleavage(HS-1200 only), DNA degradation(HS-1200 only), nuclear condensation, inhibition of proteasome activity, reduction of mitochondrial membrane potential(HS-1200 only) and the release of cytochrome c and AIF to cytosol. Between two synthetic CDCA derivatives, HS-1200 showed stronger apoptosis-inducing effect than HS-1199. Therefore HS-1200 was demonstrated to have the most efficient antitumor effect. Taken collectively, we demonstrated that a synthetic CDCA derivative HS-1200 induced caspases-dependent apoptosis via mitochondrial pathway in human oral sqauamous carcinoma cells in vitro. Our data therefore provide the possibility that HS-1200 could be considered as a novel therapeutic strategy for human orall squamous carcinoma from its poweful apoptosis-inducing activity.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.245.2-246
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• 2002

We studied on the antiproliferative effects of bile acids and their derivatives on HepG2 human hepatocellular carcinoma cells. Ursodeoxycholic acid (UDCA) and its synthetic derivative HS-1030. and chenodeoxycholic acid (CDCA) and its synthetic derivatives. HS-1199 and HS\ulcorner200, were used. We focused on the regulation of cell cycle and induction of apoptosis by these bile acid derivatives. (omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.246.1-246.1
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• 2002

We studied the effects of ursodeoxycholic acid (UDCA) and its synthetic derivatives. HS-l030 and HS-1183. and chenodeoxycholic acid (CDCA) and its synthetic derivatives, HS-1199 and HS-1200. on the human colon adenocarcinoma cell line. HT -29 (p53 mutant type). The effects on cell viability and growth were assessed by MTT assay and cell growth study. While UDCA and CDCA exhibited no significant effect, their novel derivatives inhibited the proliferation of HT-29 cell line in a concentration- and time-dependent manners. (omitted)

• Korean Journal of Clinical Pharmacy
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• v.21 no.2
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• pp.49-56
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• 2011

The family of bile acids belongs to a group of molecular species of acidic steroids with very peculiar biological characteristics. They are synthesized by the liver from cholesterol through several complementary pathways and secreted into small intestine for the participation in the digestion and absorption of fat. The bile acids are mostly confined to the territories of the so-called enterohepatic circulation, which includes the liver, the biliary tree, the intestine and the portal blood with which bile acids are returned to the liver. In patients with bile acid malabsorption, the amount of primary bile acids in the colon is increased compared to healthy controls. Although the increase in the secondary bile acids including deoxycholic acid, is reported to have the potency to affect tumorigenesis in gastrointestinal tracts, there is no firm evidence that clinically relevant concentrations of the bile acids induce cancer. The list of their physiological roles, as well as that of the pathological processes is long and still not complete. There is no doubt that many new concepts, pharmaceutical tools and pharmacological uses of bile acids and their derivatives will emerge in the near future.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.229.1-229.1
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• 2003

The anti proliferative effects of bile acids and their derivatives on HT -29 human colon cancer cells were investigated. Ursodeoxycholic acid (UDCA) and its synthetic derivatives, HS-1030 and HS-1183, and chenodeoxycholic acid (CDCA) and its synthetic derivatives, HS-1199 and HS-1200 were employed for this study. General evaluations focusing on cell cycle were conducted in HT -29 human colon adenocarcinoma cell line (p53 mutant type). (omitted)

• Journal of the Korean Applied Science and Technology
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• v.3 no.1
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• pp.49-55
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• 1986

The purpose of the study was to find an effect of Medium Chain Triglycerids (MCT) diet on cholesterol metabolism in rat. Sprague-Dawley rats were fed two different diets containing MCT(trioctanoate) and corn oil respectively. After feeding to each group for four weeks, the levels of serum and liver cholesterol, the excretion rates of fecal and biliary steroids, and also bile acid composition were investigated. The results obtained from the study are as follows : (1) The average body weight gain in MCT group was almost same as that in the corn oil group. (2) The concentration of serum cholesterol in MCT group was lower than that in the corn oil group. Therefore it is confirmed that the cholesterol lowing action of MCT diet was practically high. (3) The concentrations of liver cholesterol and Triglyceride in MCT group were almost same as that in the corn oil group. Therefore it is thought that the level of liver lipids was not influenced by the difference of diet in this study. (4) The excretion rate of fecal neutral steroid in MCT group was significantly lower than that in the corn oil group, while the rate of fecal bile acid excretion was about same in both MCT and corn oil group. (5) The composition rates of fecal bile acid such as cholic acid, chenodeoxycholic acid and deoxycholic acid, a secondary acid of cholic acid, in MCT group were significantly lower than that in the corn oil group. (6) The excretion rates of biliary cholesterol and bile acid in MCT group were significantly higher than that in the corn oil group, while the composition rates of biliary bile acid such as chenoddeoxycholic acid and deoxycholic acid in MCT group were significantly higher than that in the corn oil group.

• Journal of Nutrition and Health
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• v.33 no.8
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• pp.802-812
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• 2000

The purpose of this study was to examine the effect of resistant starch(RS) in hyperchlesterolemia and colon cancer. The subjects of this study was eight college women participating in the general starch diet(GSD) period for 5 days and resistant starch diet(RSD) period for 7 days. RSD contains 30g or the RS. On the last day of each program blood were collected. And for the last 3 days of each diet period, the amount of all the food consumed by the subjects and feces were collected. Food was measured to determine and compared the energy, protein and fat intakes. The amount of total cholesterol, HDL-cholesterol, LDL-cholesterol and volatile fatty acids in plasma and the amounts of bile acids in feces were measured by gas chromatography. The results obtained were as follows, Daily energy intake was higher in the RSD compared with the GSD, Protein and fat intakes were lower in the RSD compared with the compared with the GSD. Volatile fatty acid contents in plasma, the amounts of acetic acid, propionic acid and valeric acid were higher in the RSD compared with the GSD. The amounts of bile acids in feces, cholic acid, chenodeoxycholic acid and lithocholic acid were higher in the RSD compared with the GSD, But the amount of deoxycholic acid n the RSD period was significantly low. Secondary/primary ratios of bile acids was lower in the RSD compared with GSD, respectively. We speculate that , RS consumption decreases colonic mucosal proliferation as a result of the decreased formation of cytotoxic secondary bile acids. Thus, RS intakes may contribute the prevention of heart disease and colon cancer in humans. (Korean J Nutrition 33(8) : 802-812, 2000)

• BMB Reports
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• v.49 no.3
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• pp.173-178
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• 2016

Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O₂ for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O₂) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O₂, and by decreasing the transcription of CYP7A1.

• Journal of Oral Medicine and Pain
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• v.35 no.3
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• pp.165-175
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• 2010

Valproic acid (VPA) is a well-known anticonvulsive agent and has been used in the treatment of epilepsy for almost 30 years. VPA emerged in 1997 as an antineoplastic agent as well, when findings indicated the substance inhibited proliferation and induced differentiation of primitive neuroectocdermal tumor cells in vivo (Cinatl et al., 1997). Antitmor activity of VPA is associated with its targeting histone deacetylases. Bile acids and their synthetic derivatives induced apoptosis in various kinds of cancer cells and anticancer effects. It has been reported that the synthetic chenodeoxycholic acid (CDCA) derivatives showed apoptosis-inducing activity on various cancer cells in vitro. This study was undertaken to investigate the synergistic apoptotic effect of co-treatment with the histone deacetylases inhibitor, VPA and a CDCA derivative, HS-1200 on human osteosarcoma (HOS) cells. Cell viability was evaluated by trypan-blue exclusion. Induction and augmentation of apoptosis were confirmed by Hoechst staining, flow cytometry (DNA hypoploidy and MMP change), Westen blot analysis and immunofluorescent staining. In this study, HOS cells co-treated with VPA and HS-1200 showed several lines of apoptotic manifestation such as nuclear condensations, the reduction of MMP, the decrease of DNA content, the release of cytochrome c into cytosol, the translocation of AIF onto nuclei, and activation of caspase-7, caspase-3 and PARP whereas each single treated HOS cells did not. Although the single treatment of 1 mM VPA or $25\;{\mu}M$ HS-1200 for 48 h did not induce apoptosis, the co-treatment of them induced prominently apoptosis. Therefore our data provide the possibility that combination therapy of VPA and HS-1200 could be considered as a novel therapeutic strategy for human osteosarcoma.

• Journal of Microbiology and Biotechnology
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• v.17 no.4
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• pp.655-662
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• 2007

This study examined the effects of Lactobacillus acidophilus ATCC 43121 (LAB) on cholesterol metabolism in hypercholesterolemia-induced rats. Four treatment groups of rats (n=9) were fed experimental diets: normal diet, normal $diet+LAB(2{\times}10^6\;CFU/day)$, hypercholesterol diet (0.5% cholesterol, w/w), and hypercholesterol diet+LAB. Body weight, feed intake, and feed efficiency did not differ among the four groups. Supplementation with LAB reduced total serum cholesterol (25%) and VLDL+IDL+LDL cholesterol (42%) in hypercholesterol diet groups, although hepatic tissue cholesterol and lipid contents were not changed. In the normal diet group, cholesterol synthesis (HMG-CoA reductase expression), absorption (LDL receptor expression), and excretion via bile acids (cholesterol $7{\alpha}-hydroxylase$ expression) were increased by supplementation with LAB, and increased cholesterol absorption and decreased excretion were found in the hypercholesterol diet group. Total fecal acid sterols excretion was increased by supplementation with LAB. With proportional changes in both normal and hypercholesterol diet groups, primary bile acids (cholic and chenodeoxycholic acids) were reduced, and secondary bile acids (deoxycholic and lithocholic acids) were increased. Fecal neutral sterol excretion was not changed by LAB. In this experiment, the increase in insoluble bile acid (lithocholic acid) reduced blood cholesterol level in rats fed hypercholesterol diets supplemented with LAB. Thus, in the rat, L. acidophilus ATCC 43121 is more likely to affect deconjugation and dehydroxylation during cholesterol metabolism than the assimilation of cholesterol into cell membranes.