title: Modulatory Effects of Curcumin and Tyrphostins (AG494 and AG1478) on Growth Regulation and Viability of LN229 Human Brain Cancer Cells.
abstract: In this study we employed curcumin as a potent adjuvant agent in the treatment of human brain cancer involving selective EGFR kinase inhibitors: tyrphostins AG494 and AG1478. Aim of this work was to evaluate the effect of tested compounds on autocrine growth, cell cycle, and viability of LN229 cells, as well as to assess their proapoptotic and genotoxic properties. Our results showed that all tested compounds significantly inhibited autocrine growth of the investigated cell line in a dose dependent manner. However they are characterized by different kinetics of cell growth inhibition. Suppression of growth by the tyrphostins was completely or partially reversible in contrast to curcumin. Curcumin increased the cytostatic and/or cytotoxic potential of AG494 and AG1478. Tyrphostins did not have genotoxic properties regardless of concentration used, whereas curcumin cytotoxic and genotoxic properties were directly proportional to the concentration. Curcumin significantly increased tyrphostins cytotoxicity. The most promising of the obtained results may be the use of curcumin and tyrphostin AG494 in the treatment of cancer cells. Anticancer effect of the mixture was confirmed by increase of cytotoxic effect, decrease of viability, stimulation of apoptotic procesess, irreversible DNA damage, and decrease of the ROS in the culture of glioblastoma cells.
authors.affiliation: a Department of General Biochemistry , Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Krakow , Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bojko
authors.affiliation: a Department of General Biochemistry , Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Krakow , Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Cierniak
authors.affiliation: a Department of General Biochemistry , Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Krakow , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Adamczyk
authors.affiliation: a Department of General Biochemistry , Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Krakow , Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Ligeza
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020032:Tyrphostins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D017382:Reactive Oxygen Species; D020032:Tyrphostins; C107502:AG 494; C101044:RTKI cpd; C512478:EGFR protein, human; D066246:ErbB Receptors; D020169:Caspases; D003474:Curcumin