title: Fusaric acid induces oxidative stress and apoptosis in human cancerous oesophageal SNO cells.
abstract: Oesophageal cancer (OC) is a global problem incrementally incident among black South African males. The high incidence of OC may be due to the consumption of corn as a staple, often contaminated with mycotoxins. Fusaric acid (FA), a neglected mycotoxin, is known to disrupt mitochondrial energy metabolism, chelates divalent metal cations and induces cell death in plants. This study investigated FA-induced cytotoxicity and apoptotic induction in the SNO OC cell line. Cells were treated with FA (IC50= 78.81 μg/mL; 24 h; MTT assay) and assayed for oxidative stress and membrane damage (TBARS, LDH cytotoxicity and glutathione), apoptotic induction (ATP levels, caspase-8, -9, -3/7 activities) (Luminometry), single strand DNA and nuclear fragmentation (Comet and Hoechst assay). Additionally, relative expression of pro- and anti-apoptotic proteins were determined (Western Blotting). Significant antioxidant depletion was consistent with a concomitant increase in ROS-induced lipid peroxidation and extracellular LDH levels. FA induced apoptosis by significantly increasing Bax expression and caspase-8, -9 and -3/7 activities whilst decreasing ATP levels and Bcl-2 expression. Further, FA significantly increased comet tail lengths, PARP-1 expression and late stage apoptotic body formation in SNO cells. This study shows that FA is cytotoxic and induces increased apoptosis in SNO cells.
authors.affiliation: Discipline of Medical Biochemistry, University of KwaZulu-Natal, South Africa.
authors.forename: Nikita
authors.initials: N
authors.lastname: Devnarain
authors.affiliation: Discipline of Medical Biochemistry, University of KwaZulu-Natal, South Africa.
authors.forename: Charlette
authors.initials: C
authors.lastname: Tiloke
authors.affiliation: Discipline of Medical Biochemistry, University of KwaZulu-Natal, South Africa.
authors.forename: Savania
authors.initials: S
authors.lastname: Nagiah
authors.affiliation: Discipline of Medical Biochemistry, University of KwaZulu-Natal, South Africa. Electronic address: chutur@ukzn.ac.za.
authors.forename: Anil A
authors.initials: AA
authors.lastname: Chuturgoon
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D004249:DNA Damage; D053938:DNA Fragmentation; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology; D005669:Fusaric Acid / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D000255:Adenosine Triphosphate; D020169:Caspases; D005669:Fusaric Acid; C017807:bisbenzimide ethoxide trihydrochloride
keywords: Apoptosis; Caspases-3/7, -8, -9; Fusaric acid; Oxidative stress; SNO oesophageal cancer cells