Endogenous Metabolite; Microbial Metabolite

In the cell line MGC803, sodium deoxycholate hydrate (DCA) (100 μM) increases bile acid bursting and proliferative activity while inducing resistance to acidified bile [2]. Induced MGC803 cells with 100 μM of deoxycholdan water derivative (DCA) showed morphological alterations, a considerable increase in telomerase activity, improved cell survival, and a better reduction in cellular inflammation [2].

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Generation of MGC803 cells resistant to acidified bile acids [2]
To simulate chronic local recurrent disease in vitro, the gastric cancer cell line MGC803 was exposed to acidified medium (pH 5.5) containing 100 μmol/L DCA and CDCA. An untreated log‐growth MGC803 cell line was generated to be used as a control in normal pH media. After daily 10‐min exposure to the acidified bile acids for 60 weeks, MGC803‐resistant cells were able to survive and proliferate after 120‐min exposure.

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Bile acids (BAs), well-defined signaling molecules with diverse metabolic functions, play important roles in cellular processes associated with many cancers. As one of the most common BAs, Deoxycholic Acid (DCA) is originally synthesized in the liver, stored in the gallbladder, and processed in the gut. Deoxycholic Acid (DCA) plays crucial roles in various tumors; however, functions and molecular mechanisms of DCA in gallbladder cancer (GBC) still remain poorly characterized. Here, we analyzed human GBC samples and found that DCA was significantly downregulated in GBC, and reduced levels of DCA was associated with poor clinical outcome in patients with GBC. DCA treatment impeded tumor progression by halting cell proliferation. DCA decreased miR-92b-3p expression in an m6A-dependent posttranscriptional modification manner by facilitating dissociation of METTL3 from METTL3–METTL14–WTAP complex, which increased the protein level of the phosphatase and tensin homolog, a newly identified target of miR-92b-3p, and subsequently inactivated the PI3K/AKT signaling pathway. Our findings revealed that DCA might function as a tumor suppressive factor in GBC at least by interfering with miR-92b-3p maturation, and suggested that DCA treatment could provide a new therapeutic strategy for GBC[3].

Klb–/– mice show a modified BA composition. [1]
Given the key role of FGF21/FGFR1c/β-klotho signaling in fat oxidation, glucose uptake, and energy homeostasis, the resistance of Klb–/– mice to DIO was an unexpected observation. Further, these findings raised the question of the underlying mechanism(s). Since β-klotho is known to participate in a negative feedback loop that represses hepatic BA synthesis, we investigated whether Klb deficiency could also qualitatively impact BA homeostasis. Cyp7a1, the rate-limiting enzyme in BA synthesis, was highly overexpressed in the liver of Klb–/– mice (Figure 3A), as previously reported. Cyp8b1 (encoding sterol 12-α-hydroxylase) was also upregulated, while Cyp7b1 and Cyp27a1 (driving the alternative [acidic] BA synthesis) were underexpressed compared with WT mice (Figure 3B). This specific transcriptional pattern of BA enzymes led us to investigate differences in hepatic primary BA production and the circulating BA composition. Primary BAs are directly synthesized by the liver and converted into secondary BAs by bacterial action in the colon. In the liver, tauro-β-muricholic acid (T-βMCA) levels were decreased in Klb–/– mice (Figure 3C), confirming the downregulation of the alternative pathway. Plasma levels of both primary taurocholic acid (T-CA) and its secondary derivative deoxycholic acid (conjugated [T-DCA] and unconjugated [Deoxycholic Acid (DCA)] forms) were dramatically increased in Klb–/– mice (Figure 3, D and E). The global composition of circulating BAs was substantially modified between genotypes, with a predominance of T-CA and T-DCA in Klb–/– mice (Figure 3F).

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Resistance of Klb–/– mice to DIO is Deoxycholic Acid (DCA) driven and microbiota dependent. [1]
The massive increase of Deoxycholic Acid (DCA) and T-DCA levels in Klb–/– mice led us to investigate the specific contribution of this secondary BA to the increase in energy expenditure on HFD. To this end, we treated orally (0.5 g/l in drinking water) both Klb–/– and WT mice with vancomycin (VCM) 1 week before initiation and during the entire period of HFD consumption. VCM is a poorly absorbed antibiotic preferentially targeting Gram-positive bacteria, including Clostridium species classically described as responsible for the conversion of primary BAs into secondary BAs (such as 7α-dehydroxylation of CA into Deoxycholic Acid (DCA)). VCM treatment similarly reshapes the gut microbiota of Klb–/– and WT mice, massively decreasing both intestinal Bacteroidetes and Firmicutes content in both genotypes on HFD (Figure 7A). In contrast, Proteobacteria content was not impacted by VCM in WT and showed an increasing trend in Klb–/– mice (Figure 7A). Notably, the reshaped microbiota presents drastically reduced 7α-dehydroxylation activity, leading to residual circulating levels of DCA and T-DCA (Figure 7, B and C). Instead, the circulating BA pool is mainly composed of T-βMCA and T-CA in WT mice and of T-CA in Klb–/– mice on HFD+VCM (Figure 7D). The specific pattern of primary BA synthesis due to Klb deficiency was not affected by VCM treatment, since HFD-fed Klb–/– mice presented again higher levels of Cyp7a1 and Cyp8b1 and lower levels of Cyp7b1 compared with HFD-fed WT mice (Supplemental Figure 2A). Importantly, following VCM administration, Klb–/– mice lose their resistance to DIO. Indeed, they gain similar weight (Figure 7E) and exhibit similar fat proportion and content to that of WT (Figure 7F and Supplemental Figure 2B), despite a still lighter eWAT (Figure 7G); no major change was observed in adipose-targeted gene expression (Supplemental Figure 2, C and D), glucose tolerance (Figure 7H), or stool energy content (Figure 7I). Consistently, BAT weight (Figure 8A) and morphology (Figure 8B) were indistinguishable between Klb–/– and WT mice on HFD+VCM. VO2 (Figure 8, C and D), VCO2 (Supplemental Figure 2, E and F), and RER (Figure 8E) were also similar between Klb–/– and WT mice on HFD+VCM. Gene expression analysis in this tissue confirmed the abrogation of thermogenesis induction in Klb–/– mice on HFD+VCM, with a trend towards lower Ucp1, Dio2, and Elovl3 expression levels and significantly lower Pgc1a and Cidea expression levels (Figure 8F). We also observed a massive increase in liver weight (Figure 8G), indicating a preferential storage of fat in the liver rather than in the WAT of Klb–/– mice in the absence of Deoxycholic Acid (DCA)-driven BAT overactivity (Figure 8, H and I). This observation is also corroborated by increased hepatic expression of the scavenger receptor (fatty acid translocase, Cd36) involved in lipid accumulation under excessive fat supply (Figure 8J). Finally, hepatic gene expression of cholesterogenesis enzymes (Figure 8K) and proinflammatory cytokines (Figure 8L) remained elevated in Klb–/– mice on HFD+VCM.

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Deoxycholic Acid (DCA) suppresses GBC tumor growth by downregulating miR-92b-3p expression [3]
To further explore the critical role of miR-92b-3p in GBC, we subcutaneously inoculated ectopically expressed miR-92b-3p or the empty vector as a control in NOZ cells into nude mice, which were then fed food containing Deoxycholic Acid (DCA) or equal amount of vehicle. Compared with the empty vector, overexpression of miR-92b-3p significantly increased the cell proliferation, whereas DCA treatment could significantly attenuated miR-92b-3p-mediated tumor growth (Fig. 7a). Consistently, the tumors excised from mice with miR-92b-3p-overexpressing cells increased weights compared with those excised from mice inoculated with the empty vector, even when treated with DCA (Fig. 7b, c). Similarly, immunohistochemical measurement of Ki-67 as well as p-AKT (Ser473), p-70S6K (Thr389), and p-eIF4EBP1 (phospho T37) showed remarkably lower proliferation rates coupled with significantly decreased levels of AKT signaling pathway after treatment with DCA; miR-92b-3p overexpression partially rescued the DCA-induced growth inhibition by targeting PTEN in GBC tumors (Fig. 7d).

Drug affinity responsive targets stability (DARTS) [3]
DARTS was performed to determine the potential targets of Deoxycholic Acid (DCA). Briefly, 50 × 106 cells were lysed with M-PER supplemented with protease/phosphatase inhibitor cocktail. TNC buffer (50 mM Tris-HCL pH8.0, 50 mM NaCl, and 10 mM CaCl2) was added to the lysates. The supernatants were incubated with increasing concentration of Deoxycholic Acid (DCA) or EtOH (vehicle) for 1 h at room temperature following digestion with Pronase (1:3000) for 30 min. The digestion was terminated with protease inhibitor cocktail following ice incubation immediately. The immunoblotting signals were detected by the ECL Kit. The experiments were performed with three biological replicates.

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Cellular thermal shift assay (CETSA) [3]
Cells were pretreated with 50 μM Deoxycholic Acid (DCA) for 24 h prior to subject to the CETSA protocol. Cells were washed with PBS containing protease inhibitor cocktail and transferred into PCR tubes. The cells were subjected to heat shocked with indicated temperature for 5 min to denature proteins, then were immediately cooled down at room temperature for 5 min. All the samples were next undergone three freeze-thaw cycles to lyse cells. The supernatant was subjected to immunoblotting and the band density was detected. The experiments were performed with three biological replicates.

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miRNA expression analysis (NGS) [3]
For miRNAs-seq, total RNA of two pairs NOZ cells treated with vehicle or Deoxycholic Acid (DCA) were extracted using the miRNeasy Micro Kit. RNA-seq libraries were obtained by using the NEBnext Multiplex Small RNA Library Prep Set, following the manufacturer’s instructions. Sequencing was performed on Illumina Hi-Seq4000 platform with 50 bp single end reads using Illumina reagents according to the manufacturer’s instructions.

Cell lines and cell culture conditions [2]
MGC803 cells were cultured in Roswell Park Memorial Institute media supplemented with 10% fetal calf serum and 100 U/mL penicillin and 100 mg/mL streptomycin. To generate MGC803‐resistant cells, we adjusted the pH value of the MGC803 culture medium to the experimental conditions using the hydrochloric acid (A). The bile acids GCDA and Deoxycholic Acid (DCA) were diluted to optimal working concentrations of 100 μmol/L (B) with culture medium, and the overall pH (A + B) was adjusted to pH 5.5, simulating the gastric environment. Initially, MGC803 cells were chronically exposed to acidified medium with bile acids (A + B) for 10 min every 24 h. The experimental time and conditions were optimized in our preliminary experiments, which showed that 10 min was enough and did not result in cell damage. This procedure was repeated and it took 60 weeks for the MGC803 cells to survive and proliferate under the exposure of A + B for 120 min 12, 13. Control untreated cells were cultured in neutral RPMI medium at pH 7.4 in parallel to the resistant cells for 60 weeks. The morphological changes in MGC803 cells exposed to acidified bile acids (A+B) were documented at 30 and 60 weeks.

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Cell proliferation assays [3]
Cells were seeded in 96-well plates (2000 cells per well) treated with indicated concentration of Deoxycholic Acid (DCA) (50 μM) or vehicle and after a certain time of culturation, cell growth rate was measured using CCK-8 assays, followed by detection of the absorbance at 450 nm through Synergy 2 microplate reader.. Each experiment with three replicates was repeated three times.

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Cytotoxic assays in vitro [3]
Cells were seeded in 96-well plates (2000 cells per well) then treated with increasing concentrations of Deoxycholic Acid (DCA) for indicated times. Cell viability was assessed by the Cell Counting Kit-8 assay. The absorbance at 450 nm was measured thorough a Synergy 2 microplate reader. Each experiment with three replicates was repeated three times.

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Colony formation assay [3]
Cells were seeded in 6-well plates (1000 cells per well) for 10 days until colonies were visible, and then treated with 50 μM Deoxycholic Acid (DCA) or vehicle for 48 h. The colonies were fixed with 4% paraformaldehyde and followed by staining with 0.1% crystal violet.

For xenograft tumor model experiments, 2 × 106 cells GBC-SD or NOZ cells were resuspended with 100 μl of 1 × PBS and subcutaneously into the flanks of BALB/c nude mice (male, 4–6-week old). Six days after injection, mice were randomly allocated to control and treatment groups. All mice were sacrificed and tumors were embedded in paraffin for tissue staining. [3]

Absorption, Distribution and Excretion
Following subcutaneous injection, deoxycholic acid is rapidly absorbed. After the maximum recommended single therapeutic dose of 100 mg, post-treatment plasma concentrations return to endogenous levels within 24 hours. Accumulation is not expected with the recommended treatment regimen. Exogenous deoxycholic acid enters the enterohepatic circulation and is excreted unchanged in feces along with endogenous deoxycholic acid. The liver normally secretes approximately 24 grams of bile acids within 24 hours, dissolved in 700 to 1000 ml of bile. Most bile acids are reabsorbed in the lower small intestine and reused for secretion. The bile acid pool is approximately 2 to 5 grams. /Bile Acids/

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Metabolism/Metabolites Under normal circumstances, deoxycholic acid is not significantly metabolized.

Protein Binding
98% Interaction ... The competition between deoxycholic acid and bromosulfonphthalein for extravascular binding sites may explain the reduced distribution volume of bromosulfonphthalein in the presence of bile acids. Compounds (including deoxycholic acid) enhanced the anticoccal activity of gentamicin, monomycin, kanamycin, and neomycin. Deoxycholic acid was tested alone and as a promoter of N-nitrosobis(2-hydroxypropyl)amine-induced carcinogenesis in hamsters. This study used three groups of 5- to 6-week-old male Syrian hamsters (SYR)/NI, 10 hamsters per group, who were subcutaneously injected with 0.9% sodium chloride solution once a week for 5 weeks. Group 1 received no other treatment; Groups 2 and 3 were supplemented with 0.1% and 0.5% dichloroacetic acid (DCA), respectively, in their diet for 30 weeks. Animals were dissected at week 35. There was no significant difference in body weight between groups 1 and 2, while group 3 showed a significant decrease in body weight (P<0.005). None of the animals in these three groups exhibited liver tumors, bile duct hyperplasia, gallbladder lesions or polyps, pancreatic lesions, or pancreatic duct hyperplasia. In the promoter study, hamsters aged 5–6 weeks in all three groups (number not specified) were subcutaneously injected weekly with 500 mg/kg body weight of N-nitrosobis(2-hydroxypropyl)amine for 5 weeks. Group 4 received no further treatment, while groups 5 and 6 received 0.1% DCA (group 5) or 0.5% DCA (group 6) in their diet, respectively, for 30 weeks. Compared to group 4, both groups 5 and 6 showed a significant decrease in body weight (P<0.005). DCA significantly increased the incidence of cholangiocarcinoma. In group 5, 10 out of 19 hamsters developed cholangiocarcinoma (P<0.006), in group 6, 9 out of 25 hamsters developed cholangiocarcinoma (P<0.05), while only 1 hamster in group 4 developed cholangiocarcinoma (out of 1 out of 15 hamsters in group 4). The incidence of pancreatic cancer was significantly increased in group 5 (14/19, P<0.03). Therefore, under the conditions of this experiment, DCA alone is not carcinogenic, but it effectively promotes the development of N-nitrosobis(2-hydroxypropyl)amine-induced liver and pancreatic cancer in hamsters.

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23668196 Oral LD50 in rats: 1370 mg/kg. Behavioral changes: altered sleep duration (including altered righting reflex); behavioral changes: ataxia; lung, thoracic, or respiratory changes: other changes. Oyo Yakuri. Pharmacology and Metrology, 3(45), 1969
23668196 Rat Intraperitoneal LD50 123 mg/kg Behavioral: altered sleep duration (including altered righting reflex); Behavioral: ataxia; Lung, pleural or respiratory: other alterations Oyo Yakuri. Pharmacology and Metrology, 3(45), 1969
23668196 Rat Subcutaneous LD50 2430 mg/kg Behavioral: altered sleep duration (including altered righting reflex); Behavioral: ataxia; Lung, pleural or respiratory: other alterations Oyo Yakuri. Pharmacology and Metrology, 3(45), 1969
23668196 Rat Intravenous LD50 150 mg/kg Arzneimittel-Forschung. Drug Research., 20(323), 1970 [PMID:5467505]
23668196 Mice oral LD50 1050 mg/kg Behavior: lethargy (overall activity inhibition); Gastrointestinal: gastric ulcer or hemorrhage; Gastrointestinal: small intestinal ulcer or hemorrhage. Eisei Shikenjo Hokoku. Bulletin of the Institute of Hygienic Sciences., (103)(29), 1985 [PMID:3830311]

[1]. β-Klotho deficiency protects against obesity through a crosstalk between liver, microbiota, and brown adipose tissue. JCI Insight. 2017 Apr 20;2(8). pii: 91809.

[2]. Acidified bile acids enhance tumor progression and telomerase activity of gastric cancer in micedependent on c-Myc expression. Cancer Med. 2017 Apr;6(4):788-797.

[3]. Deoxycholic acid modulates the progression of gallbladder cancer through N6-methyladenosine-dependent microRNA maturation. Oncogene. 2020 Jun 8;39(26):4983–5000.

Sodium deoxycholate is a bile acid salt containing deoxycholic acid. Deoxycholic acid is a bile acid formed from bile acids under bacterial action, usually combined with glycine or taurine. As a surfactant, deoxycholic acid can dissolve fats to promote intestinal absorption and is itself reabsorbed; therefore, it can be used as a choleretic and surfactant. See also: Deoxycholic acid (note moved here).

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Therapeutic Uses
Cholecystic agents and choleretic drugs; surfactants
The beneficial effects of exogenous bile acids stem from their ability to lower cholesterol levels in bile and promote the dissolution of cholesterol gallstones. /Bile Acids/
Veterinary Uses: Increases bile volume without significantly altering its composition. The most effective bile acid for promoting the absorption of fats and fat-soluble vitamins.

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Deoxycholic acid is a bile acid formed by substituting hydroxyl groups at positions 3 and 12 of 5β-cholan-24-acid. It is a metabolite in human serum. It is a bile acid, dihydroxy-5β-cholanoic acid, and a C24 steroid. It is the conjugate acid of deoxycholate. Deoxycholate is a bile acid that emulsifies and dissolves dietary fats in the intestines. After subcutaneous injection, it disrupts the cell membranes of fat cells, thereby destroying fat cells in that tissue. In April 2015, the U.S. Food and Drug Administration (FDA) approved deoxycholate for the treatment of submental fat to improve facial appearance and reduce facial fullness or prominence. Marketed by Kythera Biopharma under the brand name Kybella, this drug was the first to be used to reduce submental fat and is considered safer and less invasive than surgery. ATX-101 (medical), sodium deoxycholate for subcutaneous injection, is being evaluated for reducing localized fat deposits. This includes treating superficial lipomas (benign soft tissue tumors composed of mature fat cells), fat deposits in the submental region of the face/neck, and localized fat deposits in other parts of the body. Deoxycholic acid is a naturally occurring bile acid produced by the liver and is one of the end products of cholesterol metabolism. As a natural component of the human body, deoxycholic acid salts are considered a "biocompatible" surfactant capable of dissolving fat in the small intestine. ATX-101 exhibits relative selectivity for adipose tissue. Deoxycholic acid is a metabolite of Escherichia coli (K12 strain, MG1655 strain). The E. coli metabolomics database (ECMDB) shows that deoxycholic acid is a cell-lysing agent. The physiological effect of deoxycholic acid is achieved by reducing cell membrane integrity. Deoxycholic acid has been reported in both humans and Pseudomonas syringae, and relevant data are available. The LOTUS Natural Products Database shows that deoxycholic acid is a steroidal acid, belonging to the secondary bile acid category, and possesses cell-lysing activity. Subcutaneous injection of deoxycholic acid can lead to the dissolution of adipocytes, improving the feeling of fullness caused by submental fat accumulation. Furthermore, it may also reduce fat in other subcutaneous adipose tissues. Deoxycholic acid is naturally produced by intestinal bacteria metabolizing bile acids and participates in the emulsification of dietary fats in the intestine. Deoxycholic acid is a small molecule drug that has completed the most Phase IV clinical trials (covering all indications), was first approved in 2015, and has four investigational indications. Deoxycholic acid is a bile acid formed from bile salts under bacterial action. It is usually bound to glycine or taurine. As a surfactant, deoxycholic acid dissolves fats to facilitate intestinal absorption and is itself reabsorbed, thus it can be used as a choleretic and surfactant. Bile acids are steroidal acids mainly found in the bile of mammals. The differences between different bile acids are very subtle, depending only on the presence of hydroxyl groups at positions 3, 7, and 12. Bile acids are physiological detergents that promote the excretion, absorption, and transport of fats and sterols in the intestine and liver. Bile acids are also steroidal amphiphilic molecules produced from the catabolism of cholesterol. Bile acids regulate bile flow and lipid secretion, are essential for the absorption of dietary fats and vitamins, and participate in the regulation of all key enzymes related to cholesterol homeostasis. They circulate between the liver, bile ducts, small intestine, and portal vein, forming the enterohepatic circulation. At physiological pH, they exist in anionic form and therefore require carriers for transport across the enterohepatic tissue membrane. The unique detergency properties of bile acids are crucial for the digestion and intestinal absorption of hydrophobic nutrients. Bile acids are highly toxic (e.g., damaging cell membranes), and several mechanisms exist to limit their accumulation in the blood and tissues. (A3407, A3408, A3409, A3410). A3407: St-Pierre MV, Kullak-Ublick GA, Hagenbuch B, Meier PJ: Transport of bile acids in liver and non-liver tissues. J Exp Biol. 2001 May; 204(Pt 10):1673-86. PMID: 11316487. A3408: Claudel T, Staels B, Kuipers F: Farnesol X receptor: molecular link between bile acids and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol. Oct 2005; 25(10):2020-30. Published online July 21, 2005. PMID: 16037564 A3409: Chiang JY: Regulation of liver physiology by bile acids: III. Bile acids and nuclear receptors. American Journal of Physiology: Gastrointestinal and Liver Physiology. Mar 2003; 284(3): G349-56. PMID: 12576301 A3410: Davis RA, Miyake JH, Hui TY, Spann NJ: Regulation of cholesterol-7α-hydroxylase: almost complete absence of SHP. Journal of Lipid Research. April 2002; 43(4): 533-43. PMID: 11907135
Bile acids are formed by the action of bacteria on bile acids. They are usually bound to glycine or taurine. Deoxycholic acid, as a detergent, can dissolve fat to promote intestinal absorption. It is also reabsorbed and plays a choleretic and detergent role. β-Klotho (encoded by the Klb gene) is an essential co-receptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice did not respond to the beneficial effects of FGF21 drug treatment (including stimulation of glucose utilization and thermogenesis). This study aimed to investigate the energy homeostasis of Klb-/- mice under a high-fat diet to better understand the consequences of blocking endogenous FGF15/19 and FGF21 signaling during calorie overload. Surprisingly, Klb-/- mice were resistant to diet-induced obesity (DIO) due to increased energy expenditure and brown adipose tissue (BAT) activity. Klb-/- mice not only exhibited elevated bile acid (BA) levels, but also altered composition, showing activation of the classical (neutral) BA synthesis pathway and inhibition of the alternative (acidic) pathway. Excessive production of bile acid (CA) by the liver leads to an overproduction of deoxycholic acid (DCA) from the gut microbiota. DCA can activate the TGR5 receptor, thereby stimulating thermogenic activity in brown adipose tissue (BAT). In fact, combined knockout of the Klb and Tgr5 genes, or the use of antibiotics to block the conversion of CA to DCA by bacteria, eliminated diet-induced obesity (DIO) resistance in Klb-/- mice. These results suggest that DIO resistance in Klb-/- mice is caused by high levels of DCA signaling via the TGR5 receptor. These data also suggest that the gut microbiota can modulate host thermogenesis by converting primary bile acids to secondary bile acids. Drugs or nutritional approaches that selectively modulate bile acid (BA) composition may be a promising target for the treatment of metabolic disorders. [1] c-Myc overexpression is associated with a variety of malignancies, including gastric cancer. This study reports that acidified bile acids can promote tumor progression and telomerase activity in gastric cancer in vitro and in vivo by activating c-Myc. We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to detect the expression levels of c-Myc mRNA and protein in 10 primary gastric cancer samples and 5 locally recurrent gastric cancer samples. To construct the MGC803 drug-resistant cell line, we exposed the gastric cancer cell line MGC803 to bile salts (100 μmol/L glycocholic acid and deoxycholic acid) in acidic medium (pH 5.5) for 10 minutes daily for 60 weeks. As a control, we cultured MGC803 cells in a medium without acid or bile salts for 60 weeks. After 60 weeks, we analyzed the cell morphology, proliferation, colony formation, and apoptosis of the MGC803 drug-resistant cells. To determine the role of c-Myc in tumor progression and telomere aging in MGC803 resistant cells, we constructed a xenograft model in nude mice and measured the volume of xenografts and in vivo telomerase activity. The levels of c-Myc and hTERT protein and mRNA in locally recurrent gastric cancer samples were significantly higher than those in primary gastric cancer samples. MGC803 resistant cells showed significant phenotypic changes under normal growth conditions, with increased cell clusters and acinar numbers, enhanced cell viability and colony formation ability in vitro, and reduced apoptosis. Using the c-Myc inhibitor 10058-F4, we found that these phenotypic changes depended on c-Myc activation. MGC803 resistant cells also showed c-Myc-dependent xenograft growth and enhanced telomerase activity in vivo. In summary, these observations support the hypothesis that acidification of bile acids promotes tumor progression and telomerase activity in gastric cancer, and that these effects depend on c-Myc activity. These findings suggest that acidification of bile acids plays an important role in the malignant progression of locally recurrent gastric cancer. [2]

C24H39NAO4

414.56

414.274

C, 69.53; H, 9.48; Na, 5.55; O, 15.44

302-95-4

Deoxycholic acid;83-44-3;Deoxycholic acid-d4;112076-61-6;Deoxycholic acid-d5;52840-14-9;Deoxycholic acid-13C;52886-37-0;Deoxycholic acid sodium hydrate;145224-92-6;Deoxycholic acid-d6

23668196

White to off-white solid powder

1.128g/cm3

547.1ºC at 760 mmHg

357-365 °C

3.143

2

4

4

29

612

10

C[C@H](CCC(=O)[O-])[C@H]1CC[C@@H]2[C@@]1([C@H](C[C@H]3[C@H]2CC[C@H]4[C@@]3(CC[C@H](C4)O)C)O)C.[Na+]

FHHPUSMSKHSNKW-SMOYURAASA-M

InChI=1S/C24H40O4.Na/c1-14(4-9-22(27)28)18-7-8-19-17-6-5-15-12-16(25)10-11-23(15,2)20(17)13-21(26)24(18,19)3;/h14-21,25-26H,4-13H2,1-3H3,(H,27,28);/q;+1/p-1/t14-,15-,16-,17+,18-,19+,20+,21+,23+,24-;/m1./s1

sodium;(4R)-4-[(3R,5R,8R,9S,10S,12S,13R,14S,17R)-3,12-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoate

Sodium deoxycholate; 302-95-4; Deoxycholic acid sodium salt; Sodium desoxycholate; Deoxycholate sodium; Desoxycholate sodium; Sodium 7-deoxycholate; Na-Desoxycholat;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~333.33 mg/mL (~804.08 mM)
DMSO : ~6.25 mg/mL (~15.08 mM)

Solubility in Formulation 1: ≥ 0.62 mg/mL (1.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 0.62 mg/mL (1.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 0.62 mg/mL (1.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 6.2 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 50 mg/mL (120.61 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)