Swietenolide isolated from Swietenia macrophylla King in Hook seeds shows in vitro anti-colorectal cancer activity through inhibition of mouse double minute 2 (MDM2) homolog.

Swietenia macrophylla King in Hook (SM) is known to have several medicinal properties. Chloroform extracts of SM seeds (SMCE) as well as two isolated limonoids swietenine (1) and swietenolide (2) showed significant in vitro anti-CRC activity in human colon carcinoma (HCT116) cell line. 2 (IC50 = 5.6 µM) was found to be two times more potent than 1 (IC50 = 10 µM). Both compounds showed anti-CRC activity through inhibition of the Mouse Double Minute 2 homolog (MDM2) of the MDM2-p53 pathway. The Selectivity Index (S.I.) of isolated compounds 1 and 2 for cancer cells were about 6.6 and 12.8 fold respectively which was significantly better than the S.I. of the extract (S.I. ∼1.5).

Starch, gallic acid, their inclusion complex and their effects in diabetes and other diseases-A review.

Starch is the most important energy-providing component of food. It is useful for maintaining the structural and rheological consistency of food, ad thus, in turn, is responsible for maintaining the freshness of food. Polyphenols are present in plant products in huge amounts as secondary metabolites. Gallic acid, one of the potent plant polyphenols, has been reported to have excellent anti-inflammatory, antioxidative, anticarcinogenic, microbicidal, and antidiabetic properties. Till date, very few articles on the starch-polyphenol inclusion complex are present. Quite a few hypotheses have been proposed as to how the formation of an inclusion complex of starch with polyphenol can slower the digestion or the hydrolysis of starch. The efficient qualities of starch-polyphenol systems, such as reduced starch digestion, lower blood glucose and preserving food freshness, have formed a necessity for investigation in this area. The focus of this review centers on the recent research on starch-polyphenol interactions and starch-gallic acid inclusion complexes in native and extruded food systems, as well as how the production of these complexes can aid in the treatment of diseases, particularly diabetes mellitus.

Green-synthesized gold nanoparticles from black tea extract enhance the chemosensitivity of doxorubicin in HCT116 cells via a ROS-dependent pathway.

Green gold nanoparticles (GNPs) were prepared from black tea extract (BTE) and used to examine the chemosensitivity of doxorubicin in colon cancer cell line HCT116. BTE-GNPs were prepared by a single-step method and characterized by UV-Vis spectroscopy, FTIR spectroscopy, SEM, DLS and zeta-potential. The MTT assay was performed to determine the cytotoxicity of HCT116 cells and also normal kidney cells HEK293. Apoptosis and ROS generation were investigated by flow cytometry. The inhibition of ROS levels by the inhibitor NAC was determined by both spectrofluorimetry and confocal microscopy. Expression levels of pro- and anti-apoptotic proteins were determined by a western blot technique. BTE-GNPs significantly enhanced the cytotoxic effect of DOX with its co-treatment in HCT116 cells. The cytotoxic effect of BTE-GNP + DOX was involved in apoptosis via a ROS-dependent pathway by enhancing the pro-apoptotic protein expression. Therefore, our results indicated that green gold nanoparticles of black tea extract (BTE-GNP) may be potent chemosensitizers of doxorubicin.

S-Benzyl cysteine based cyclic dipeptide super hydrogelator: Enhancing efficacy of an anticancer drug via sustainable release.

Peptide-based low molecular weight supramolecular hydrogels hold promising aspects in various fields of application especially in biomaterial and biomedical sciences such as drug delivery, wound healing, tissue engineering, cell proliferation, and so on due to their extreme biocompatibility. Unlike linear peptides, cyclic peptides have more structural rigidity and tolerance to enzymatic degradation and high environmental stability which make them even better candidates for the above-said applications. Herein, a new small cyclic dipeptide (CDP) cyclo-(Leu-S-Bzl-Cys) (P1) consisting of L-leucine and S-benzyl protected L-cysteine was reported which formed a hydrogel at physiological conditions (at 37°C and pH = 7.46). The hydrogel formed from the cyclic dipeptide P1 showed very good tolerance towards environmental parameters such as pH and temperature and was seen to be stable for more than a year without any deformation. The hydrogel was thermoreversible and stable in the pH range 6-12. Mechanical strength of P1 hydrogel was measured by rheology experiments. Atomic force microscopy (AFM) and field emission scanning electron microscopy (FE-SEM) images revealed that, in aqueous solvents, P1 self-assembled into a highly cross-linked nanofibrillar network which immobilized water molecules inside the cages and formed the hydrogel. The self-assembled cyclic dipeptide acquired the antiparallel ß-sheet secondary structure, which was evident from CD and Fourier transform infrared (FT-IR) studies. The ß-sheet arrangement and formation of amyloid fibrils were further established by ThT binding assay. Furthermore, P1 was able to form a hydrogel in the presence of the anticancer drug 5-fluorouracil (5FU), and sustainable release of the drug from the hydrogel was measured in vitro. The hydrogelator P1 showed almost no cytotoxicity towards the human colorectal cancer cell line HCT116 up to a considerably high concentration and showed potential application in sustainable drug delivery. The co-assembly of 5FU and P1 hydrogel exhibited much better anticancer activity towards the HCT116 cancer cell line than 5FU alone and decreased the IC50 dose of 5FU to a much lower value.

Chitosan-Decorated PLGA-NPs Loaded with Tannic Acid/Vitamin E Mitigate Colon Cancer via the NF-κB/ß-Cat/EMT Pathway.

Colon cancer is the second highest contributor of cancer-related deaths throughout the world. Treatment strategies with tannic acid and vitamin E are envisaged as desirable and safe owing to their robust antioxidative and anti-inflammatory potential. In the present report, these bioactives have been nanoencapsulated in poly(d,l-lactide-co-glycolic acid) (PLGA) formulations for maintaining sustained release and ensuring enhanced bioavailability. Capping of nanoparticles (NPs) with chitosan was done for enhanced anticancer efficacy and tumor targeting. CS-PLGA-TA-E, administered intraperitoneally, significantly inhibited tumor number and tumor volume and normalized colon histology in the colon cancer. Tissue distribution studies showed that TA/E content from CS-PLGA-TA-E was present in a higher concentration in the tumor tissue than the concentration of TA/E content from PLGA-TA-E or free TA or free E. Also, the TA/E content from all of the treatment groups showed its highest concentration in the tumor compared to other organs. Antioxidant enzymes and proinflammatory cytokines (TNF-α, IL-1ß, IL-6) were inhibited by CS-PLGA-TA-E. CS-PLGA-TA-E inhibited markers for tumor growth (EGFR-PI3K-AKT), inflammation (NF-κB/Stat3), ß-catenin signaling (ß-catenin, c-myc, cyclin D1), EMT (E-cadherin, N-cadherin, vimentin), and apoptosis (Bcl-2) in a significantly greater way as compared with PLGA-TA-E, TA, or E. CS-PLGA-TA-E NPs can be considered promising anticancer drugs for colon cancer.

Tannic acid and vitamin E loaded PLGA nanoparticles ameliorate hepatic injury in a chronic alcoholic liver damage model via EGFR-AKT-STAT3 pathway.

Aim: Tannic acid and vitamin E loaded-poly D, L-lactide-co-glycolic acid (PLGA) nanoparticles (NP) were developed to achieve hepatoprotection in alcoholic liver disease mice model. Materials & methods: PLGA NPs were formed by emulsion solvent evaporation and characterized and delivered to mice. Histology studies were performed, serum enzyme levels of AST, ALT and inflammatory cytokines were checked using ELISA kits. Confocal microscopy and western blot analysis were utilized to determine protein expression levels, and docking studies were performed for interaction analysis. Results: PLGA NPs provided hepatoprotection by reducing inflammatory load, preventing reactive oxygen species generation and apoptosis, as well as by inhibiting the EGFR-AKT-STAT3 pathway. Conclusion: PLGA NPs of tannic acid and vitamin E could be a future medication for alcoholic liver disease treatment.

Tannic acid-stabilized gold nano-particles are superior to native tannic acid in inducing ROS-dependent mitochondrial apoptosis in colorectal carcinoma cells via the p53/AKT axis.

Gold nanoparticle formulated tannic acid (AuNP-TA) was synthesized, and its anticancer activity was compared to that of free tannic acid (TA). The half maximal inhibitory concentration (IC50) was reduced by half when cell lines were treated with AuNP-TA as compared to IC50 values upon free TA treatment. Both showed better cytotoxic activity in HCT116 cell line as compared to MCF7 and HepG2. AuNP-TA induced death of HCT116 cells was associated with characteristic apoptotic changes. At the same treatment dose, AuNP-TA generated more ROS, caused a more extensive DNA damage and promoted higher expression of p53 and p21 than TA. Treatment with AuNP-TA regulated generation of p53 and ROS bi-directionally. Binding studies showed that TA lowered the expression of Akt, which inhibited the survival of colon cancer cells. Also, cell cycle arrest at the G2/M phase, enhanced expression of caspase-3/9, Bak, and Bax, loss of mitochondrial membrane potential, and enhanced level of cytosolic cytochrome c were observed in AuNP-TA treated HCT116 cells. Thus, AuNP-TA is more efficient than TA in inducing apoptotic cell death of HCT116 cells via the ROS/P53/Akt axis.

Synthesis of Triazole-Substituted Quinazoline Hybrids for Anticancer Activity and a Lead Compound as the EGFR Blocker and ROS Inducer Agent.

A series of triazole-substituted quinazoline hybrid compounds were designed and synthesized for anticancer activity targeting epidermal growth factor receptor (EGFR) tyrosine kinase. Most of the compounds showed moderate to good antiproliferative activity against four cancer cell lines (HepG2, HCT116, MCF-7, and PC-3). Compound 5b showed good antiproliferative activity (IC50 = 20.71 µM) against MCF-7 cell lines. Molecular docking results showed that compound 5b formed hydrogen bond with Met 769 and Lys 721 and π-sulfur interaction with Met 742 of EGFR tyrosine kinase (PDB ID: 1M17). Compound 5b decreases the expression of EGFR and p-EGFR. It also induces apoptosis through reactive oxygen species generation, followed by the change in mitochondrial membrane potential.