title: In vitro antiproliferative and cytotoxic activities of novel kojic acid derivatives: 5-benzyloxy-2-selenocyanatomethyl- and 5-methoxy-2-selenocyanatomethyl-4-pyranone.
abstract: Some kojic acid (KA) derivatives and selenium containing compounds possess antiproliferative properties. The present study tested novel selenocyanatomethyl derivatives of KA for growth inhibitory and LDH cytotoxic activities. Human skin carcinoma (A431) and human breast carcinoma (MCF7) cells were treated with 5-benzyloxy-2-selenocyanatomethyl-4-pyranone (P763) and 5-methoxy-2-selenocyanatomethyl-4-pyranone (P764) in selected concentrations for 24, 48 and 72 h. Cell viability tests aimed at intracellular injury of mitochondria (MTT) and lysosomes (neutral red uptake, NR) revealed (a) higher growth inhibitory activity of the benzyloxy-selenocyanatomethyl derivative of KA (P763) compared with the methoxy derivative (P764) in both cell lines, (b) an intensified effect with time of exposure (MTT test only). The results demonstrate that NR cell survival/viability assay is more sensitive than the MTT test to detect subcellular changes induced by test compounds. Cell membrane integrity determined by LDH leakage confirmed an exaggerated cytotoxic effect of P763 but similar sensitivity of both cell lines to membrane injury. The ED50 values for all three tests used indicate that injury of intracellular mitochondria and lysosomes precedes the loss of membrane integrity. Cell growth inhibitory activities of new selenium containing kojic acid derivatives are preferentially aimed at the intracellular compartment rather than the plasma membrane and enlarge the group of antiproliferative active compounds.
authors: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, 833 07 Bratislava, Slovak Republic. ueenfick@savba.sk <ueenfick@savba.sk>
authors: Maria
authors: M
authors: Fickova
authors: Eliska
authors: E
authors: Pravdova
authors: Lars
authors: L
authors: Rondhal
authors: Michal
authors: M
authors: Uher
authors: Julius
authors: J
authors: Brtko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008247:Lysosomes / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D013997:Time Factors
chemical_list: C529965:5-benzyloxy-2-selenocyanataomethyl-4-pyranone; C529966:5-methoxy-2-selenocyanatomethyl-4-pyranone; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D011753:Pyrones