Molecular mechanisms of antitumor activity of the polymeric form of niclosamide with respect to human colorectal cancer cells

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Vol. 11; no. 3; pp. 301 - 307
• Main Authors: Zhirnik, A. S., Semochkina, Yu. P., Moskaleva, E. Yu, Krylov, N. I., Tubasheva, I. A., Kuznetsov, S. L., Vorontsov, E. A.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-07-2017; Springer Nature B.V
• Subjects: Antitumor activity; Bioorganic Chemistry; Biotechnology; Cell cycle; Chemistry; Chemistry and Materials Science; Colorectal cancer; Colorectal carcinoma; Cytotoxicity; Embryo fibroblasts; Fibroblasts; Lungs; Medicinal Chemistry; Mitochondria; Molecular modelling; Niclosamide; Reactive oxygen species; Rhodamine; Superoxide; Tumor cell lines; Tumor cells; polymeric form of niclosamide; poly(lactic-co-glycolic) acid; niclosamide; colorectal cancer; cell cycle; reactive oxygen species
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S1990750817030131

Using poly(lactic-co-glycolic) acid a polymeric form of niclosamide (PFN) has been developed and its antitumor activity against human colorectal cancer cell lines SW837, Caco-2, COLO 320 HSR has been investigated in comparison with free niclosamide. PFN was shown to be more cytotoxic against cancer cells and less cytotoxic against normal cells (human embryonic lung fibroblasts) as compared to niclosamide. Free niclosamide and PFN share a common mechanism of the cytotoxic action on tumor cells, which is associated with mitochondrial damage (evaluated as a decrease in rhodamine 123 accumulation), and increased levels of reactive oxygen species, particularly mitochondrial superoxide anion, causing oxidative damage of intracellular targets. The action of niclosamide and PFN was accompanied by G
0
/G
1
cell cycle arrest.