title: Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation.
abstract: Curcumin is a natural compound that exhibits a wide range of beneficial effects, among them the anti-tumor activity. Recently it was shown that curcumin may be efficient against drug resistant tumor cells. The goal of our investigation was to examine if human laryngeal carcinoma cells resistant to carboplatin display sensitivity to curcumin, as compared to parental cells, and if this sensitivity is altered, to determine the molecular mechanisms that are responsible for it. We found that carboplatin resistant 7T cells were also cross resistant to curcumin. After the treatment with equimolar concentration of curcumin, 7T cells exhibited lower intracellular accumulation of curcumin which coincided with reduced formation of reactive oxygen species (ROS), diminished lipid and DNA damage followed by reduced induction of apoptosis and expression of heat shock protein 70 (Hsp70), as compared to parental HEp-2 cells. However, after the treatment with equitoxic concentration of curcumin, intracellular accumulation and all the explored downstream effects were similar in both cell lines suggesting that resistance of 7T cells to curcumin was based on its reduced intracellular accumulation. Since curcumin accumulates mostly in the membranes, we explored the fatty acid composition of both cell lines, but we did not find any difference between them.
authors.affiliation: Division of Molecular Biology, Ruder Boskovic Institute, Bijenicka cesta 54, HR-10000 Zagreb, Croatia.
authors.forename: Sanjica
authors.initials: S
authors.lastname: Rak
authors.forename: Tamara
authors.initials: T
authors.lastname: Cimbora-Zovko
authors.forename: Goran
authors.initials: G
authors.lastname: Gajski
authors.forename: Klara
authors.initials: K
authors.lastname: Dubravčić
authors.forename: Ana-Marija
authors.initials: AM
authors.lastname: Domijan
authors.forename: Ivančica
authors.initials: I
authors.lastname: Delaš
authors.forename: Verica
authors.initials: V
authors.lastname: Garaj-Vrhovac
authors.forename: Drago
authors.initials: D
authors.lastname: Batinić
authors.forename: Jasna
authors.initials: J
authors.lastname: Sorić
authors.forename: Maja
authors.initials: M
authors.lastname: Osmak
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D016190:Carboplatin / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004249:DNA Damage; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005227:Fatty Acids / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D005227:Fatty Acids; D018840:HSP70 Heat-Shock Proteins; D017382:Reactive Oxygen Species; D016190:Carboplatin; D003474:Curcumin