In vitro toxicity of naringin and berberine alone, and encapsulated within PMMA nanoparticles.

Phytochemical compounds, such as naringin and berberine, have been used for many years due to their antioxidant activities, and consequently, beneficial health effects. In this study, it was aimed to evaluate the antioxidant properties of naringin, berberine and poly(methylmethacrylate) (PMMA) nanoparticles (NPs) encapsulated with naringin or berberine and their possible cytotoxic, genotoxic, and apoptotic effects on mouse fibroblast (NIH/3 T3) and colon cancer (Caco-2) cells. According to the results of the study, it was found that the 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition antioxidant activity of naringin, berberine, and naringin or berberine encapsulated PMMA NPs, was significantly increased at higher tested concentrations due to the antioxidant effects of naringin, berberine and naringin or berberine encapsulated PMMA NPs. As a result of the cytotoxicity assay, after 24-, 48- and 72-h of exposure, all of the studied compounds caused cytotoxic effects in both cell lines. Genotoxic effects of studied compounds were not registered at lower tested concentrations. Based on these data, polymeric nanoparticles encapsulated with naringin or berberine may contribute to new treatment approaches for cancer, but further in vivo and in vitro research is required.

Selective toxicity and type of cell death induced by various natural and synthetic compounds in oral squamous cell carcinoma.

This article reviews the selective toxicity and type of cell death induced in oral squamous cell carcinoma (OSCC) by hundreds of natural and synthetic compounds. Flavonoids, coumarins, tannins, ketones and other synthetic compounds showed low to moderate tumor-specific cytotoxicity against human OSCC cell lines as compared with normal human oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast), whereas anthracyclines, nocobactins and cyclic alpha, beta-unsaturated compounds showed much higher tumor-specific cytotoxicity. No strict relationship was found between the tumor-specific cytotoxicity and apoptosis induction. There was a considerable variation in drug-sensitivity among 5 OSCC cell lines. OSCC cell lines were generally resistant to apoptosis induction. The cytotoxic activity of antitumor agents is affected by various factors related to the compounds themselves, the cells and their environments. Systematization of the relationship between these factors and tumor-specificity may contribute in the quest for more active compounds.

Modulation of drug-resistant membrane and apoptosis proteins of breast cancer stem cells by targeting berberine liposomes.

The recurrence of breast cancer is associated with drug-resistance of cancer stem cells (CSCs), while overexpression of cell membrane ATP-binding cassette (ABC) transporters and resistance of mitochondrial apoptosis-related proteins are responsible for the drug-resistance of CSCs. The targeting berberine liposomes were developed to modulate the resistant membrane and mitochondrial proteins of breast CSCs for the treatment and prevention of breast cancer relapse. Evaluations were performed on human breast CSCs and CSC xenografts in nude mice. The targeting berberine liposomes were shown to cross the CSC membrane, inhibit ABC transporters (ABCC1, ABCC2, ABCC3, ABCG2) and selectively accumulate in the mitochondria. Furthermore, the pro-apoptotic protein Bax was activated while the anti-apoptotic protein Bcl-2 was inhibited resulting in opening of the mitochondrial permeability transition pores, release of cytochrome c, and activation of caspase-9/caspase-3 enzymes. Significant efficacy of the administrations in mice was observed, indicating that the targeting berberine liposomes are a potential therapy for the treatment and prevention of breast cancer relapse arising from CSCs.