Induction of oxidative stress as a possible mechanism by which geraniol affects the proliferation of human A549 and HepG2 tumor cells

Geraniol (GOH), like other plant-derived natural bioactive compounds, has been found to possess antiproliferative properties that are essential to cope with malignant tumors. However, the mechanisms of molecular action are not fully elucidated. The aim of this study was to evaluate the effect of GOH on some oxidative parameters in human tumor cell lines (HepG2 and A549). Cytotoxicity evaluated in cell lines by the MTT assay, genotoxicity by the comet assay, and lipid peroxidation by the TBARS. The activities of antioxidant the enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione- S-transferase (GST), were also analyzed. Additionally, intracellular reactive oxygen species (ROS), nitric oxide, and lactate production were determined in HepG2 cells. Both tumor cell lines showed a clear concentration-dependent response to GOH inseveral of the parameters evaluated. Lipids turned out to be more sensitive than DNA to oxidative damage induced by GOH. TBARS levels increased with respect to control (p<0.05) by 33% and 122% in HepG2 and A549 cells, respectively treated with 200 μM GOH. However, GOH caused a statistically significant decrease in SOD and CAT activities in HepG2 cells only. GST was not affected in any cell lines. GOH induced the production of ROS but not nitric oxide in HepG2, which shows that ROS were mainly responsible for oxidative damage. Lactate release increased statistically significantly compared to control (p<0.001), by 41% and 86% at 200 and 800 μM GOH respectively, showing that this monoterpene also affected the glycolytic pathway in HepG2 cells. These results suggest that oxidative stress could mediate the anti-proliferative effects of GOH in HepG2 and A549 cells.Fil: Crespo, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Rodenak Kladniew, Boris Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Castro, María Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Soberón, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Lavarias, Sabrina Maria Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; Argentin

Respiration

Aerobic respiration is a process, where energy rich compounds are enzymatically hydrolyzed and oxidized. A part of the energy released is trapped in the form of ATP and made available for use in energy consuming processes of plant cells. The general process can be summarized as under: n (CH2O) + n O2 + n H2O -->   n CO2 + 2n H2O + Energy (ATP) The first step in aerobic respiration occurs when glucose (or other storage carbohydrate) is metabolized through glycolisis or oxidative pentose phosphate pathway, where intermediates (i.e. amino acids, nucleotides) and NADPH are produced (see Chapter 20). In plants, malate and pyruvate are the end products of glycolisis and malate is most important. Malate and pyruvate are transported from the cytosol to the mitochondria where they are oxidised in the TAC cycle. Complete oxidation of one molecule of malate yields 5 molecules of NADH and one molecule of FADH2, then one molecule of ATP. NADH and FADH2 donate their electrons to the electron transport chain. Aerobic respiration occurs in both light and darkness. It can cause a considerable decrease in dry weight of plant tissues by itself. Another respiration occurs only in green tissues and is light-dependent. It involves enzymatic oxidation of glycolic acid generated in photosynthesis to CO2: Glycolate oxidase CH2OH-COOH   +   O2           ----->                              CHO-COOH + H2O2                            Glycolic acid                                                            Glyoxylic acid CHO-COOH + H2O2      --->                   HCOOH + CO2 + H2O                                     Glyoxylic acid                                          Formic acid Energy released during this process, known as photorespiration, is not useful for the cell. Whole photorespiration process occurs in chloroplast, peroxisomes and mitochondria and is not the subject of this chapter. Nevertheless, several comprehensive texts on photorespiration and protocols to study it are available. Tissues of higher plants can respirate in the absence of oxygen through a process called fermentation and CO2 is also one of the end products. However, organic molecules respired are not completely oxidized to CO2 and H2O and many reduced end products are generated, but ATP production is very small. This chapter provides techniques to measure aerobic respiration and fermentation in plant tissues.Fil: Sampietro, Diego Alejandro. Universidad Nacional de Tucumán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Sgariglia, Melina Araceli. Universidad Nacional de Tucumán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Soberón, Maria Victoria. Universidad Nacional de Tucumán; ArgentinaFil: Vattuone, Marta Amelia. Universidad Nacional de Tucumán; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán; ArgentinaFil: Quiroga, Emma Nelly. Universidad Nacional de Tucumán; Argentin