Anticancer therapeutic potential of phosphorylated galactosylated chitosan against N-nitrosodiethyl amine-induced hepatocarcinogenesis.

Chitosan is a natural polyfunctional polymer that can be modified to achieve compounds with tailored properties for targeting and treating different cancers. In this study, we report the development and anticancer potential of phosphorylated galactosylated chitosan (PGC). The synthesized compound was characterized by FT-IR, NMR, and mass spectroscopy. The interaction of PGC with asialoglycoprotein receptors (ASGPR) and cellular internalization in HepG2 cells was studied using in silico and uptake studies respectively. PGC was evaluated for its metal chelating, ferric ion reducing, superoxide, and lipid peroxide (LPO) inhibiting potential. Further, anticancer therapeutic potential of PGC was evaluated against N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma in a mice model. After development of cancer, PGC was administered to the treatment group (0.5 mg/kg bw, intravenously), once a week for 4 weeks. Characterization studies of PGC revealed successful phosphorylation and galactosylation of chitosan. A strong interaction of PGC with ASGP-receptors was predicted by computational studies and cellular internalization studies demonstrated 98.76 ± 0.53% uptake of PGC in the HepG2 cells. A good metal chelating, ferric ion reducing, and free radical scavenging activity was demonstrated by PGC. The anticancer therapeutic potential of PGC was evident from the observation that PGC treatment increased number of tumor free animals (50%) (6/12) and significantly (p ≤ 0.05) lowered tumor multiplicity as compared to untreated tumor group.

Electrical conductivity spectra of hepatic tumors reflect hepatocellular carcinoma progression in mice.

Background:Electrical impedance spectroscopy is a technique which evaluates differences in dielectric properties of tissues for cancer identification.Methods:Murine hepatic cancer model was developed by intraperitoneal administration of N-nitrosodiethylamine to male BALB/c mice. Tumors obtained were evaluated for their conductivity in frequency range of (4 Hz-5 MHz). All tumors were subjected to histopathological grading and parameters such as free spacing, necrosis, and cell density were estimated on histological slides. The status of gap junctions and gap junction intercellular communication (GJIC) were studied using enzyme-linked immunosorbent assay, immunohistochemistry, dye transfer assay, and electron microscopy.Results:Histopathological investigation revealed the presence of moderately to poorly-differentiated hepatocellular carcinoma (HCC) in mice. All types of tumors showed higher electrical conductivity than normal liver tissue in frequency range (4 Hz-1 kHz). However, in frequency range (10 kHz-5 MHz) only poorly-differentiated tumors showed higher conductivity compared to normal tissue. The most prominent findings in moderately-differentiated and poorly-differentiated HCC were increased visible free spaces and necrosis respectively. The status of cell gap junctions were significantly deteriorated in tumors and a corresponding significant reduction in GJIC was also observed. These biological indicators were correlated with electrical conductivity of hepatic tumors.Conclusion:Variations in electrical conductivity spectra of hepatic tumors reflect progression of HCC.General significance:Future studies can be planned to perform hierarchical clustering of dielectric parameters with more number of tumor samples to establish dielectric spectroscopy-based classification or staging of hepatic tumors.