maltodextrin and Colorectal-Neoplasms

On the basis of preliminary in vitro experience, we assessed whether an enriched nutritional formulation with estrogen receptor (ER)-beta agonist and anti-inflammatory properties may prevent inflammation-associated colorectal cancer (CRC) in an animal model. Study sample enclosed 110 C57BL/6J male mice. Forty underwent dietary supplement safety assessment (20 standard diet and 20 enriched formulation). Seventy were treated with azoxymethane (AOM)/dextran sulfate sodium and divided into two groups: 35 received standard diet and 35 enriched formulation (curcumin, boswellic acids, silymarin and maltodextrins). Miniature colonoscopy demonstrated colitis and solid lesion development in five mice/group 100 days after first AOM injection. Mice were killed after 10 days. In each group, four subgroups received intraperitoneal bromodeoxyuridine (BrdU) injection at 24th/48th/72nd/96th hour before killing. Anti-inflammatory effect and chemoprevention were evaluated by lesion number/size, histological inflammation/dysplasia/neoplasia assessment, pro-inflammatory cytokine messenger RNA (mRNA), ER-beta/ER-alpha/BrdU immunohistochemistry and TUNEL immunofluorescence. Standard formulation assumption was associated with colon shortening compared with enriched one (P = 0.04), which reduced solid lesion number and size (P < 0.001 for both), histological inflammation score (P = 0.04), pro-inflammatory cytokine mRNA expression (P < 0.001), number of low-grade dysplasia (LGD; P = 0.03) and high-grade dysplasia (P < 0.001) areas. CRC was observed in 69.6% in standard and 23.5% in enriched formulation assuming animals (P < 0.001). Enriched formulation induced lower ER-alpha expression in CRC (P < 0.001) and higher ER-beta expression in LGD (P < 0.001) being associated to higher epithelial turnover (BrdU; P<0.001) in normal mucosa and increased apoptosis in LGD and CRC (P < 0.001 for both). Our results are promising for a successful anti-inflammatory and chemopreventive effect of enriched formulation in CRC arising from inflamed tissue.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Azoxymethane; Chemoprevention; Colitis; Colon; Colonoscopy; Colorectal Neoplasms; Curcumin; Cytokines; Dextran Sulfate; Disease Models, Animal; Food, Fortified; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Polysaccharides; Real-Time Polymerase Chain Reaction; Receptors, Estrogen; Silymarin; Triterpenes

To enhance oral bioavailability and chemotherapeutic efficacy of naringenin (NG) by fabricating the NG-encapsulated Soluthin-maltodextrin-based nanocarrier (NC) system.. NG-encapsulated nanocarriers (NG/NCs) were developed, and in vitro physicochemically characterized. Furthermore, Wistar rats were used to evaluate the pharmacokinetic profile. Furthermore, in vitro and in vivo colorectal cancer efficacy was evaluated in BALB/c mice-bearing colon-26 cells.. The NG/NCs demonstrated favorable mean particle size (176 ± 2.35 nm) and percent entrapment efficiency (70.83 ± 4.55%), respectively. The oral bioavailability was found to be approximately 116-fold higher and in vitro cytotoxicity exhibited approximately 21-fold reduction as compared with pure NG. Moreover, optimized NG/NCs demonstrated significant tumor suppression compared with pure NG in vivo.. The NG/NCs would be an efficient formulation for enhancing oral bioavailability and chemotherapeutic efficacy of NG.

Topics: Administration, Oral; Animals; Antineoplastic Agents; Biological Availability; Cell Line, Tumor; Colon; Colorectal Neoplasms; Drug Carriers; Female; Flavanones; Humans; Male; Mice, Inbred BALB C; Nanoparticles; Particle Size; Polysaccharides; Rats, Wistar; Rectum

Resistant maltodextrin Fibersol-2 is a soluble and fermentable dietary fiber that is Generally Recognized As Safe (GRAS) in the United States. We tested whether Fibersol-2 contains anti-tumor activity. Human colorectal cancer cell line, HCT116, and its isogenic cells were treated with FIbersol-2. Tumor growth and tumorigenesis were studied in vitro and in vivo. Apoptotic pathway and generation of reactive oxygen species (ROS) were investigated. We discovered that Fibersol-2 significantly inhibits tumor growth of HCT116 cells by inducing apoptosis. Fibersol-2 strongly induces mitochondrial ROS and Bax-dependent cleavage of caspase 3 and 9, which is shown by isogenic HCT116 variants. Fibersol-2 induces phosphorylation of Akt, mTOR in parental HCT116 cells, but not in HCT116 deficient for Bax or p53. It prevents growth of tumor xenograft without any apparent signs of toxicity in vivo. These results identify Fibersol-2 as a mechanism-based dietary supplement agent that could prevent colorectal cancer development.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Colorectal Neoplasms; Dietary Supplements; HCT116 Cells; Humans; Mice; Mitochondria; Polysaccharides; Reactive Oxygen Species; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays