title: Early loss of mitochondrial inner transmembrane potential in khat-induced cell death of primary normal human oral cells.
abstract: Previous studies suggest the use of khat, a psychostimulant plant used by millions of people in Middle East and Africa, as risk factor for oral cancer. We previously reported that khat is able to induce adverse affects, as cell cycle arrest and apoptosis, in normal human oral cells cultured in vitro. This study further investigates the more specific role played by mitochondria in khat-induced cell death and the kinetics of the events involved in this process. Exposure of primary normal human oral keratinocytes and fibroblasts to khat extract resulted in a swift and sustained decrease of the mitochondrial inner transmembrane potential occurring within 0.5-1h. Loss of mitochondrial membrane potential preceded all other biochemical and morphologic changes, and was associated with a significant decrease in cell survival. Subsequently, apoptosis-inducing factor was released from mitochondria into cytosol and relocated to nucleus. Cyclosporine A and bongkrekic acid delayed both the loss of mitochondrial inner transmembrane potential and the onset of cell death. This study describes a novel mechanism of khat-induced cell death in primary normal oral keratinocytes and fibroblasts involving an early pivotal effect on mitochondrial function and integrity.
authors: Section of Pathology, The Gade Institute, Faculty of Medicine and Odontology, University of Bergen, Norway.
authors: Ochiba M
authors: OM
authors: Lukandu
authors: Therese
authors: T
authors: Bredholt
authors: Evelyn
authors: E
authors: Neppelberg
authors: Bjørn T
authors: BT
authors: Gjertsen
authors: Anne C
authors: AC
authors: Johannessen
authors: Olav K
authors: OK
authors: Vintermyr
authors: Daniela Elena
authors: DE
authors: Costea
mesh_terms: D000328:Adult; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D029754:Catha / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D007700:Kinetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009061:Mouth Mucosa / Q000166:cytology*
chemical_list: D051033:Apoptosis Inducing Factor; D016895:Culture Media, Serum-Free