ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) is considered as the third leading cause of cancer-related deaths, in spite of great advances in its treatment. The carbohydrate polymers, exopolysaccharides (EPSs), showed anticancer activity in diverse cancers. OBJECTIVE: The purpose of this study is to investigate a panel of 43 apoptotic proteins to assess the possible apoptotic induction effect of bacterial EPSs showing promising cytotoxic effects in HepG2 cells in our previous study, in an attempt to introduce exopolysaccharides as new source for cancer treatment. MATERIALS AND METHODS: Apoptosis-related proteins panel were examined through the analysis of Human Apoptosis Antibody Array-Membrane (43 targets). RESULTS: EPS-6 induces apoptosis through upregulation of different pro-apoptotic proteins as cytochrome C (9.52 fold) and tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL-R1) (153.49 fold). EPS-RS induces apoptosis through up regulation of second mitochondria-derived activator of caspases (SMAC) (15.75 fold) and the six insulin-like growth factors binding proteins (IGFBP-1 through - 6) (76.81 fold, 7.68 fold, 55.15 fold, 4.9 × 107 fold, 29.69 fold, and 28.92 fold), respectively. CONCLUSION: Our results suggested that EPS-6 and EPS-RS could be considered as promising agents in hepatocellular carcinoma treatment.
Subject(s)
Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Polysaccharides, Bacterial/pharmacology , Apoptosis/drug effects , Apoptosis Regulatory Proteins/metabolism , Aquatic Organisms/chemistry , Carcinoma, Hepatocellular/metabolism , Cytochromes c/metabolism , Hep G2 Cells , Humans , Insulin-Like Growth Factor Binding Proteins/metabolism , Liver Neoplasms/metabolism , Mitochondrial Proteins/metabolism , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/isolation & purification , Receptor Activator of Nuclear Factor-kappa B/metabolism , Signal TransductionABSTRACT
Objective: Exopolysaccharides gained attention as new source for cancer treatment as recent treatments cause side effects and multidrug resistance. Polysaccharides containing sulfur and uronic acids exhibited antioxidant activity, by restoring cell redox regulation, thus inhibiting cell proliferation and cancer formation. Following this context, our study was performed to assess the cytotoxic activity of exopolysaccharides produced by novel Egyptian marine bacterial strains on HepG2 cells. Methods: Bacteria were isolated, purified and cultured through routine microbiological techniques. 16S rRNA gene amplification and sequence analyses, Fourier Transform Infra-red (FTIR), Identification of monosugars by HPLC molecular weight estimation, sulfur content determination and neutral red uptake assay were utilized. Results: BLAST showed that the isolates were related to the Bacillus sp. FTIR analysis indicated that the four EPSs under study contained sulfur as substituent functional group but with different percentage in each EPS. The highest sulfur percentage (46%) appeared in the EPS-6 that was produced by Bacillus flexus isolated from the Mediterranean Sea. HPLC showed that EPSs contained uronic acids which appeared as glucuronic and galacturonic acid in the low molecular weight EPS-6 (4.296×104 g mol-1). Arabinose appeared besides the glucuronic and galacturonic acid residues. EPS-6 showed the highest cytotoxicity, IC50 (218 µg ml-1) which could be correlated to the presence of sulfure and uronic acids in its structure. Conclusion: The novel Firmicutes from the Egyptian saline habitat produced EPSs of cytotoxic activity on hepatocellular carcinoma.
ABSTRACT
Anticancer agents featuring hybrid molecules can improve effectiveness and diminish drug resistance. The current study aimed to introduce newly synthesized heterocyclic steroids of promising anticancer effects loaded in polyethylene glycol (PEG)â¢based nanoparticles form. Several heterocyclic steroids (1-9) were synthesized via multicomponent reactions (MCRs) and confirmed via the analytical and spectral data. Compounds 1, 2, 3, 4, 5, 6, 7 and 9, were investigated individually in their free and PEG based nano-size hybrid forms as anticancer agents against three human cell lines: hepatocellular carcinoma cells (HepG2); breast cancer cells (MCF-7); and colon cancer cells (HCT116). The neutral red supravital dye uptake assay was employed. Compound 6 in its PEG based nano-size form exhibited the best cytotoxic effects against HepG2 and HCT116 cell lines, with IC50 values of 2.44 µmol/l and 2.59 µmol/l, respectively. In addition, it demonstrated a low IC50 value against MCF-7 (3.46µmol/l) cells. This study introduced promising anticancer agents acting through conversion into PEG-based nanoparticles.
