title: Anti-proliferative and apoptosis-triggering potential of disulfiram and disulfiram-loaded polysorbate 80-stabilized PLGA nanoparticles on hepatocellular carcinoma Hep3B cell line.
abstract: There is an emerging trend to restudy known drugs for their anti-cancer potential. One such anti-alcoholic drug, disulfiram, with significant anti-cancer potential was studied for its efficacy against Hep3B cell lines, an in vitro model of hepatocellular carcinoma. Simultaneously, we intended to study the effect of polysorbate 80-stabilized PLGA nanoparticles and its DSF-loaded counterpart. Cell and nuclear staining, comet assay, flow cytometry and Western blots were performed. Results suggest that cell proliferation was inhibited by DSF and its PLGA nanoparticles through cell cycle arrest, triggering activation of apoptotic pathways that culminates with cell death. DSF loaded nanoparticles when compared with free DSF, showed significantly lesser effect due to its sustained drug-releasing property, while empty nanoparticles showed negligible influence on Hep3B cells. Our results suggest that DSF alone contributes to cell death, while polysorbate 80-stabilized PLGA nanoparticles show sustained drug release patterns that would potentially lower dosage regimens.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India.
authors.forename: Muddasarul
authors.initials: M
authors.lastname: Hoda
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India.
authors.forename: Sankar
authors.initials: S
authors.lastname: Pajaniradje
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Shakya
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India.
authors.forename: Kumaravel
authors.initials: K
authors.lastname: Mohankumar
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India; Interdisciplinary Programme for Life Sciences, Pondicherry University, Puducherry, India; Department of Biotechnology, University of Madras, Guindy Campus, Chennai, Tamilnadu, India. Electronic address: ruks2k2@yahoo.co.in.
authors.forename: Rukkumani
authors.initials: R
authors.lastname: Rajagopalan
mesh_terms: D065086:Acetaldehyde Dehydrogenase Inhibitors / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004221:Disulfiram / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D053758:Nanoparticles; D011136:Polysorbates
chemical_list: D065086:Acetaldehyde Dehydrogenase Inhibitors; D011136:Polysorbates; D004221:Disulfiram
keywords: Apoptosis; Biodegradable nanoparticles; Cancer; Disulfiram; PLGA