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Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism. [ABSTRACT FROM AUTHOR]

The increasing demands of renewable energy have led to the critical emphasis on novel enzymes to enhance cellulose biodegradation for biomass conversion. To identify new cellulases in the ruminal bacterium Fibrobacter succinogenes, a cell extract of cellulose-grown cells was separated by ion-exchange chromatography and cellulases were located by zymogram analysis and identified by peptide mass fingerprinting. An atypical family 9 glycoside hydrolase (GH9), Cel9D, with less than 20% identity to typical GH9 cellulases, was identified. Purified recombinant Cel9D enhanced the production of reducing sugar from acid swollen cellulose (ASC) and Avicel by 1.5- to 4-fold when mixed separately with each of four other glucanases, although it had low activity on these substrates. Cel9D degraded ASC and cellodextrins with a degree of polymerization higher than 2 to glucose with no apparent endoglucanase activity, and its activity was restricted to [beta]-1 [right arrow] 4-1inked glucose residues. It catalyzed the hydrolysis of cellulose by an inverting mode of reaction, releasing glucose from the nonreducing end. Unlike many GH9 cellulases, calcium ions were not required for its function. Cel9D had increased [k.sub.cat]/[K.sub.m] values for cello-oligosaccharides with higher degrees of polymerization. The [k.sub.cat]/[K.sub.m] value for cellohexaose was 2,300 times higher than that on cellobiose. This result indicates that Cel9D is a 1,4-[beta]-D-glucan glucohydrolase (EC 3.2.1.74) in the GH9 family. Site-directed mutagenesis of Cel9D identified Asp166 and Glu612 as the candidate catalytic residues, while Ser168, which is not present in typical GH9 cellulases, has a crucial structural role. This enzyme has an important role in crystalline cellulose digestion by releasing glucose from accessible cello-oligosaccharides.

Comparative analysis of binding of intact glucose-grown Fibrobacter succinogenes strain S85 cells and adhesion-defective mutants AD1 and AD4 to crystalline and acid-swollen (amorphous) cellulose showed that strain S85 bound efficiently to both forms of cellulose while mutant Ad1 bound to acid-swollen cellulose, but not to crystalline cellulose, and mutant Ad4 did not bind to either. One- and two-dimensional electrophoresis (2-DE) of outer membrane cellulose binding proteins and of outer membranes, respectively, of strain S85 and adhesion-defective mutant strains in conjunction with mass spectrometry analysis of tryptic peptides was used to identify proteins with roles in adhesion to and digestion of cellulose. Examination of the binding to cellulose of detergent-solubilized outer membrane proteins from S85 and mutant strains revealed six proteins in S85 that bound to crystalline cellulose that were absent from the mutants and five proteins in Ad1 that bound to acid-swollen cellulose that were absent from Ad4. Twenty-five proteins from the outer membrane fraction of cellulose-grown F. succinogenes were identified by 2-DE, and 16 of these were up-regulated by growth on cellulose compared to results with growth on glucose. A protein identified as a Cl-stimulated cellobiosidase was repressed in S85 cells growing on glucose and further repressed in the mutants, while a cellulose-binding protein identified as pilin was unchanged in S85 grown on glucose but was not produced by the mutants. The candidate differential cellulose binding proteins of S85 and the mutants and the proteins induced by growth of S85 on cellulose provide the basis for dissecting essential components of the cellulase system of F. succinogenes.

Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase-[alpha] (G6Pase-[alpha]), whose activity--limited to [...]

Cancer is caused by uncontrolled cell division and is a leading cause of mortality worldwide. Oenothera odorata (O. odorata) extract is used in herbal medicine to inhibit inflammation, but its potential anti-tumor properties have not been fully evaluated. Here, we demonstrated that O. odorata extract inhibits the proliferation of lung adenocarcinoma and melanoma cell lines In Vitro, and also inhibits the growth of melanoma cells In Vivo. After partitioning the extract with n-hexane, chloroform, ethyl acetate, and n-butanol, it was found that the butanol-soluble (OOB) and water-soluble (OOW) fractions of O. odorata extract are effective at inhibiting tumor cell growth In Vivo although OOW is more effective than OOB. Interestingly, these fractions did not inhibit the growth of non-cancerous cells. The anti-proliferative effects of the OOW fraction were found to be mediated by inhibition of glycolysis and cellular respiration. UPLC of both fractions showed two major common peaks, which were predicted to be hydrolyzable tannin-related compounds. Taken together, these data suggest that O. odorata extract has anti-tumor properties, and the molecular mechanism involves metabolic alterations and inhibition of cell proliferation. O. odorata extract therefore holds promise as a novel natural product for the treatment of cancer. [ABSTRACT FROM AUTHOR]

Cellular metabolism generally refers to biochemical processes that produce or consume energy within the cell. Recent studies have established that aberrant metabolic states caused by internal or external stresses and genetic mutations are intertwined with several human pathologies. Gaining insight into these metabolic alterations is, therefore, essential for understanding the pathophysiology of various diseases. Glycogen storage disease type Ib (GSD‐Ib) is an autosomal recessive disorder characterized by hypoglycemia, excessive glycogen accumulation in the liver and kidney, neutropenia, neutrophil dysfunction, and inflammatory bowel disease. GSD‐Ib is caused by a deficiency of glucose‐6‐phosphate transporter (G6PT). Recently, it was reported that deficiency of G6PT also leads to the aberrant proliferation and differentiation of mesenchymal stem cells and impaired regulatory T‐cell function. This review describes the broad impact of altered cellular metabolism resulting from a lack of G6PT activity on cellular function and considers the prospects of developing novel approaches for GSD‐Ib treatment. [ABSTRACT FROM AUTHOR]