mónica polo - Academia.edu (original) (raw)

Papers by mónica polo

Research paper thumbnail of Prevención de los cambios hepáticos inducidos por fructosa mediante co-administración de exendina-4 y sitagliptina a través de la inhibición de la actividad de fructosaquinasa vía receptor de GLP-1

Tercera Época, Dec 1, 2013

Research paper thumbnail of Effects of lovastatin on the fatty acid desaturation in a human lung mucoepidermoid carcinoma grown in nude mice

Biochemistry and molecular biology international, 1996

The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was... more The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was studied in a human lung mucoepidermoid carcinoma (HLMC) grown in nude mice. After administration of a diet supplemented with 25 mg% (w/w) lovastatin for 30 days the growth of HLMC was not inhibited. Liver and tumor phospholipid/cholesterol ratio was increased in lovastatin group but serum cholesterol was unaffected. Treatment with lovastatin increased delta 5 and delta 9 desaturation in tumor microsomes, whereas delta 6 desaturation did not change in tumors of treated mice. The changes were not reflected in the fatty acid composition of total tumor lipids.

Research paper thumbnail of Efecto del aceite de la cáscara de mandarina sobre la proliferación de células mononucleares Raw 264.7 y su diferenciación a células espumosas

Tercera Época, Oct 1, 2017

Research paper thumbnail of Evaluación de la actividad antiproliferativa y citotóxica de monoterpenos en células tumorales y normales

Tercera Época, May 1, 2016

Research paper thumbnail of Composición química y propiedades antiproliferativas del aceite esencial demandarina ( Citrus reticulata ) y salvia morada ( Lippia alba )

Tercera Época, Nov 1, 2014

Research paper thumbnail of Acción de fitoquímicos sobre la vía del mevalonato y la síntesis de fosfolípidos en células tumorales humanas

Tercera Época, Dec 1, 2013

Research paper thumbnail of Modulación de Ras, arresto del ciclo celular e inducción de apoptosis por linalool en células hepáticas tumorales

Tercera Época, Dec 1, 2013

Research paper thumbnail of Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line

Cell Biochemistry and Function, Jul 7, 2011

Simvastatin is a competitive inhibitor of 3‐hydroxymethylglutaryl coenzyme A reductase activity, ... more Simvastatin is a competitive inhibitor of 3‐hydroxymethylglutaryl coenzyme A reductase activity, whereas geraniol is a monoterpene with multiple pharmacologic effects on mevalonate metabolism. Both of them inhibit growth and proliferation of many cell lines. The present study was designed to determine the action of geraniol, in combination with simvastatin, by assessing their effects in vitro on human hepatocarcinoma cell line (Hep G2). The treatment of Hep G2 cells with concentrations of simvastatin or geraniol that did not inhibit cell proliferation (5 µmol·l‐1 of simvastatin and 50 µmol·l‐1 of geraniol) resulted in a significant inhibition of cell proliferation. We also examined the effect of simvastatin, geraniol and the combination of both on the biosynthesis of lipids from [14C]‐acetate. Our results demonstrate that the combination of simvastatin and geraniol synergistically inhibited cholesterol biosynthesis and proliferation of Hep G2 cell line, contributing to a better understanding of the action of a component of essential oils targeting a complex metabolic pathway, which would improve the use of drugs or their combination in the fight against cancer and/or cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.

Research paper thumbnail of Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR

Palacky Univ, Jul 1, 2012

Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation ... more Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation with selectivity against tumor cells. Isoprenoids are also potent suppressors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalyzing the main rate-limiting step of the mevalonate pathway and cholesterol synthesis in mammalian cells. HMGCR inhibition decreases the elevated cholesterol levels widely required by rapidly growing cancer cells, inhibits the prenylation of certain growth-regulatory proteins that play a key role in controlling cell proliferation, and induces apoptosis. Geraniol, an acyclic isoprenoid monoterpene, occurring in the essential oils of several aromatic plants, is thought to represent a new class of chemotherapeutic agent. In order to evaluate the antiproliferative property of geraniol in vitro and in vivo, and to understand the mechanisms by which this monoterpene inhibits cell growth, we studied its effects on human- lung epithelial (A549) and human-hepatoma cell lines (HepG2) as well as on A549 implanted in nude mice fed with 50-75 mmol.GOH/kg diet for 21 days. Viability and proliferation of cells incubated with 200 -600 µM geraniol were determined by trypan-blue?dye-exclusion cell and by the MTT assay. Apoptosis was determined by TUNEL assay and caspase-3 activity. HMGCR expression was analyzed by real-time RT-PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. Lipid synthesis was assessed by incorporation of [14C]acetate. Our results showed that 200 -600 µM geraniol inhibits cell proliferation in both cell lines. HMGCR-mRNA expression was significantly increased in liver cells but HMGCR-protein levels and enzymatic activity, along with cholesterol synthesis, became significantly decreased. These results showed that geraniol down-regulates the enzyme by a posttranscriptional mechanism. In vivo assays geraniol significantly reduced tumor growth and significantly enhanced apoptosis of tumor cells. Treated host-mice also showed a decreased in HMGGR-protein levels and cholesterogenesis. The relevance of this work resides in the finding that geraniol both decreases HMGCR levels and inhibits tumor cell proliferation in vitro and in vivo suggesting that geraniol has a great potential as a natural drug against cancer.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: Galle, Marianela Edith. 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: Bravo, Margarita G. de. 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: Polo, Mónica P.. 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"; Argentin

Research paper thumbnail of Evaluación del efecto antioxidante de monoterpenos presentes en aceites esenciales y su potencial antiaterogénico

Research paper thumbnail of Geraniol: aportes para el tratamiento de hipercolesterolemia y cáncer basado en nutrigenómica

Introducción Las propiedades quimioterapéuticas e hipolipemiantes de los compuestos de origen veg... more Introducción Las propiedades quimioterapéuticas e hipolipemiantes de los compuestos de origen vegetal han recibido gran atención con el objetivo de encontrar sustancias que puedan ser usadas como alternativas a las drogas convencionales. Los monoterpenos -presentes en aceites esenciales de frutas cítricas y plantas aromáticasestán siendo activamente muy estudiados debido a su bajo costo, buena biodisponibilidad y escasa toxicidad. Se demostró que muchos de ellos ejercen múltiples efectos sobre la vía del mevalonato (VM) en células de mamíferos que podrían causar los efectos terapéuticos deseados. La VM produce isoprenoides que son incorporados en diversos productos finales como colesterol, dolicol y ubiquinona o utilizados por preniltransferasas para las modificaciones postraduccionales de ciertas proteínas de la superfamilia Ras, GTPasas pequeñas que regulan importantes procesos celulares, como proliferación celular, diferenciación, apoptosis y organización del citoesqueleto. La et...

Research paper thumbnail of Uptake and metabolic conversion of saturated and unsaturated fatty acids in Hep2 human larynx tumor cells

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2001

Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The c... more Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The cells were incubated with either a saturated (palmitic) or a polyunsaturated (linoleic, a-linolenic and eicosatrienoic (n-6)) radioactive fatty acid (0.66 mM, 24 h).The best incorporation capacity was observed in the linoleic acid followed by a-linolenic, palmitic and eicosatrienoic acids. All fatty acids tested were anabolized to higher derivatives within their own family. Palmitic acid was primarily monodesaturated rather than elongated, proving to have a very active D9 desaturase activity.With respect to polyunsaturated acid metabolism, the conversion of a-linolenic acid to higher homologs, although better than linoleic acid, occurred far less efficiently than that observed in other non-highly undifferentiated human tumor cells.This impairment in higher polyunsaturated fatty acid biosynthesis, reflected in the low levels of arachidonic acid in the fatty acid composition, would not reside in the D5 desaturation step since Hep2 cells can readily convert eicosatrienoic acid into arachidonic acid. Considering the potential regulatory role of specific polyunsaturated fatty acids in the cell proliferative control, the knowledge of the metabolism of fatty acids in this human tumor cell would be important for designing future experiments in order to clarify the mechanism involved in balance, proliferation and cell death.

Research paper thumbnail of Inhibición de la proliferación de células tumorales humanas por agentes que afectan la vía del mevalonato: efecto sinérgico entre monoterpenos y estatinas

Tercera Epoca, Oct 1, 2011

Research paper thumbnail of Proliferación celular y metabolismo lipídico de células tumorales tratadas con el aceite esencial de un quimiotipo de Lippia alba procedente de Costa Rica

Tercera Epoca, Oct 1, 2010

Research paper thumbnail of Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways

Biochemistry and Cell Biology, 2013

Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitum... more Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitumor activity against several cell lines. We investigated the effects of geraniol on lipid metabolic pathways involved in Hep-G2 cell proliferation and found that geraniol inhibits the mevalonate pathway, phosphatidylcholine biosynthesis, cell growth, and cell cycle progression (with an arrest occurring at the G0/G1 interphase) and increases apoptosis. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in cholesterol synthesis, was inhibited at the transcriptional and posttranscriptional levels, as assessed by real-time RT–PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. That geraniol decreased cholesterogenesis but increased the incorporation of [14C]acetate into other nonsaponifiable metabolites indicated the existence of a second control point between squalene and cholesterol involved in redirecting the flow of choleste...

Research paper thumbnail of Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2

Biochemistry and Cell Biology, 2006

Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a d... more Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor activity against several cell lines. We have studied the effects of geraniol on growth, fatty-acid metabolism, and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 µmol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase activity of these cells. At the same concentrations, it increased the incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol-treated cells incorporated less14C-acetate into nonsaponifiable lipids, inhibiting its incorporation into cholesterol but not into squalene and lanosterol. This is indicative of an inhibition in cholesterol synthesis at a step between lanosterol and cholesterol, a fact confirmed when cells were incubated with3H-mevalonate. The incorporation of3H-mevalonate into protein was also inhibi...

Research paper thumbnail of Simvastatin Effects on a Human Lung Carcinoma and Cholesterol Homeostasis of Host and Non-Host Mice

Archives Of Physiology And Biochemistry, 2001

In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor g... more In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor growth and cholesterol homeostasis of host and non-host mice, we maintained a human lung mucoepidermoid carcinoma (HLMC) in nude mice, treating these animals with Simvastatin for 33 days. The drug increased the total activity of hepatic HMG-CoA reductase without affecting the cholesterolemia. Non-treated host animals presented lower serum, tissue and microsomal hepatic cholesterol than non-host animals. These differences disappeared when animals were treated with Simvastatin, though the induction of the reductase activity at mid-dark was higher in non-host than in host animals. Simvastatin produced no significant effects on both final tumor volume and body weight. Synthesis and cholesterol homeostasis restoration induced by liver and tumoral reductase would account for no effect on the HLMC growth after a long treatment with Simvastatin.

Research paper thumbnail of Efecto sinérgico entre monoterpenos en la proliferación de células tumorales

Tercera Epoca, Dec 1, 2010

Research paper thumbnail of Aceites esenciales y su actividad antiproliferativa sobre líneas tumorales humanas

Tercera Epoca, Oct 1, 2011

Research paper thumbnail of Las gotas lípidicas nucleares constituyen un nuevo dominio nuclear

Introduccion El nucleo celular (N) es la adquisicion evolutiva que define a las celulas eucariota... more Introduccion El nucleo celular (N) es la adquisicion evolutiva que define a las celulas eucariotas, y es donde se lleva a cabo la replicacion, la transcripcion, el splicing del pre-RNAm y el ensamblaje de los ribosomas, entre otros procesos celulares. El N es una estructura altamente dinamica, formada por distintos compartimentos y dominios funcionales intranucleares que, a diferencia de los citoplasmaticos, no estan rodeados por membranas, como el nucleolo, los Cuerpos de Cajal, los compartimentos de splicing-factor (Speckles), cuerpos de “promyelocytic leucemia oncoproteins” y los cuerpos nucleares entre otros. Hemos determinado que los lipidos representan el 16% de los componentes nucleares, a su vez el 84% corresponde a fosfolipidos (PL) y el 16% a lipidos neutros. Los PL se encuentran principalmente en la envoltura nuclear mientras que los lipidos endonucleares se encuentran enriquecidos en lipidos neutros.

Research paper thumbnail of Prevención de los cambios hepáticos inducidos por fructosa mediante co-administración de exendina-4 y sitagliptina a través de la inhibición de la actividad de fructosaquinasa vía receptor de GLP-1

Tercera Época, Dec 1, 2013

Research paper thumbnail of Effects of lovastatin on the fatty acid desaturation in a human lung mucoepidermoid carcinoma grown in nude mice

Biochemistry and molecular biology international, 1996

The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was... more The effect of lovastatin, a hypocholesterolemic drug, on tumor growth and desaturase activity was studied in a human lung mucoepidermoid carcinoma (HLMC) grown in nude mice. After administration of a diet supplemented with 25 mg% (w/w) lovastatin for 30 days the growth of HLMC was not inhibited. Liver and tumor phospholipid/cholesterol ratio was increased in lovastatin group but serum cholesterol was unaffected. Treatment with lovastatin increased delta 5 and delta 9 desaturation in tumor microsomes, whereas delta 6 desaturation did not change in tumors of treated mice. The changes were not reflected in the fatty acid composition of total tumor lipids.

Research paper thumbnail of Efecto del aceite de la cáscara de mandarina sobre la proliferación de células mononucleares Raw 264.7 y su diferenciación a células espumosas

Tercera Época, Oct 1, 2017

Research paper thumbnail of Evaluación de la actividad antiproliferativa y citotóxica de monoterpenos en células tumorales y normales

Tercera Época, May 1, 2016

Research paper thumbnail of Composición química y propiedades antiproliferativas del aceite esencial demandarina ( Citrus reticulata ) y salvia morada ( Lippia alba )

Tercera Época, Nov 1, 2014

Research paper thumbnail of Acción de fitoquímicos sobre la vía del mevalonato y la síntesis de fosfolípidos en células tumorales humanas

Tercera Época, Dec 1, 2013

Research paper thumbnail of Modulación de Ras, arresto del ciclo celular e inducción de apoptosis por linalool en células hepáticas tumorales

Tercera Época, Dec 1, 2013

Research paper thumbnail of Geraniol and simvastatin show a synergistic effect on a human hepatocarcinoma cell line

Cell Biochemistry and Function, Jul 7, 2011

Simvastatin is a competitive inhibitor of 3‐hydroxymethylglutaryl coenzyme A reductase activity, ... more Simvastatin is a competitive inhibitor of 3‐hydroxymethylglutaryl coenzyme A reductase activity, whereas geraniol is a monoterpene with multiple pharmacologic effects on mevalonate metabolism. Both of them inhibit growth and proliferation of many cell lines. The present study was designed to determine the action of geraniol, in combination with simvastatin, by assessing their effects in vitro on human hepatocarcinoma cell line (Hep G2). The treatment of Hep G2 cells with concentrations of simvastatin or geraniol that did not inhibit cell proliferation (5 µmol·l‐1 of simvastatin and 50 µmol·l‐1 of geraniol) resulted in a significant inhibition of cell proliferation. We also examined the effect of simvastatin, geraniol and the combination of both on the biosynthesis of lipids from [14C]‐acetate. Our results demonstrate that the combination of simvastatin and geraniol synergistically inhibited cholesterol biosynthesis and proliferation of Hep G2 cell line, contributing to a better understanding of the action of a component of essential oils targeting a complex metabolic pathway, which would improve the use of drugs or their combination in the fight against cancer and/or cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.

Research paper thumbnail of Geraniol inhibits tumor cell proliferation in vitro and in vivo by posttranscriptional regulation of HMGCR

Palacky Univ, Jul 1, 2012

Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation ... more Plant isoprenoids are widely known as nontoxic natural compounds that inhibit cell proliferation with selectivity against tumor cells. Isoprenoids are also potent suppressors of the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the enzyme catalyzing the main rate-limiting step of the mevalonate pathway and cholesterol synthesis in mammalian cells. HMGCR inhibition decreases the elevated cholesterol levels widely required by rapidly growing cancer cells, inhibits the prenylation of certain growth-regulatory proteins that play a key role in controlling cell proliferation, and induces apoptosis. Geraniol, an acyclic isoprenoid monoterpene, occurring in the essential oils of several aromatic plants, is thought to represent a new class of chemotherapeutic agent. In order to evaluate the antiproliferative property of geraniol in vitro and in vivo, and to understand the mechanisms by which this monoterpene inhibits cell growth, we studied its effects on human- lung epithelial (A549) and human-hepatoma cell lines (HepG2) as well as on A549 implanted in nude mice fed with 50-75 mmol.GOH/kg diet for 21 days. Viability and proliferation of cells incubated with 200 -600 µM geraniol were determined by trypan-blue?dye-exclusion cell and by the MTT assay. Apoptosis was determined by TUNEL assay and caspase-3 activity. HMGCR expression was analyzed by real-time RT-PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. Lipid synthesis was assessed by incorporation of [14C]acetate. Our results showed that 200 -600 µM geraniol inhibits cell proliferation in both cell lines. HMGCR-mRNA expression was significantly increased in liver cells but HMGCR-protein levels and enzymatic activity, along with cholesterol synthesis, became significantly decreased. These results showed that geraniol down-regulates the enzyme by a posttranscriptional mechanism. In vivo assays geraniol significantly reduced tumor growth and significantly enhanced apoptosis of tumor cells. Treated host-mice also showed a decreased in HMGGR-protein levels and cholesterogenesis. The relevance of this work resides in the finding that geraniol both decreases HMGCR levels and inhibits tumor cell proliferation in vitro and in vivo suggesting that geraniol has a great potential as a natural drug against cancer.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: Galle, Marianela Edith. 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: Bravo, Margarita G. de. 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: Polo, Mónica P.. 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"; Argentin

Research paper thumbnail of Evaluación del efecto antioxidante de monoterpenos presentes en aceites esenciales y su potencial antiaterogénico

Research paper thumbnail of Geraniol: aportes para el tratamiento de hipercolesterolemia y cáncer basado en nutrigenómica

Introducción Las propiedades quimioterapéuticas e hipolipemiantes de los compuestos de origen veg... more Introducción Las propiedades quimioterapéuticas e hipolipemiantes de los compuestos de origen vegetal han recibido gran atención con el objetivo de encontrar sustancias que puedan ser usadas como alternativas a las drogas convencionales. Los monoterpenos -presentes en aceites esenciales de frutas cítricas y plantas aromáticasestán siendo activamente muy estudiados debido a su bajo costo, buena biodisponibilidad y escasa toxicidad. Se demostró que muchos de ellos ejercen múltiples efectos sobre la vía del mevalonato (VM) en células de mamíferos que podrían causar los efectos terapéuticos deseados. La VM produce isoprenoides que son incorporados en diversos productos finales como colesterol, dolicol y ubiquinona o utilizados por preniltransferasas para las modificaciones postraduccionales de ciertas proteínas de la superfamilia Ras, GTPasas pequeñas que regulan importantes procesos celulares, como proliferación celular, diferenciación, apoptosis y organización del citoesqueleto. La et...

Research paper thumbnail of Uptake and metabolic conversion of saturated and unsaturated fatty acids in Hep2 human larynx tumor cells

Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA), 2001

Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The c... more Research on fatty acid metabolism in cultured human larynx tumor cells Hep2 was carried out.The cells were incubated with either a saturated (palmitic) or a polyunsaturated (linoleic, a-linolenic and eicosatrienoic (n-6)) radioactive fatty acid (0.66 mM, 24 h).The best incorporation capacity was observed in the linoleic acid followed by a-linolenic, palmitic and eicosatrienoic acids. All fatty acids tested were anabolized to higher derivatives within their own family. Palmitic acid was primarily monodesaturated rather than elongated, proving to have a very active D9 desaturase activity.With respect to polyunsaturated acid metabolism, the conversion of a-linolenic acid to higher homologs, although better than linoleic acid, occurred far less efficiently than that observed in other non-highly undifferentiated human tumor cells.This impairment in higher polyunsaturated fatty acid biosynthesis, reflected in the low levels of arachidonic acid in the fatty acid composition, would not reside in the D5 desaturation step since Hep2 cells can readily convert eicosatrienoic acid into arachidonic acid. Considering the potential regulatory role of specific polyunsaturated fatty acids in the cell proliferative control, the knowledge of the metabolism of fatty acids in this human tumor cell would be important for designing future experiments in order to clarify the mechanism involved in balance, proliferation and cell death.

Research paper thumbnail of Inhibición de la proliferación de células tumorales humanas por agentes que afectan la vía del mevalonato: efecto sinérgico entre monoterpenos y estatinas

Tercera Epoca, Oct 1, 2011

Research paper thumbnail of Proliferación celular y metabolismo lipídico de células tumorales tratadas con el aceite esencial de un quimiotipo de Lippia alba procedente de Costa Rica

Tercera Epoca, Oct 1, 2010

Research paper thumbnail of Transcriptional and posttranscriptional inhibition of HMGCR and PC biosynthesis by geraniol in 2 Hep-G2 cell proliferation linked pathways

Biochemistry and Cell Biology, 2013

Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitum... more Geraniol, present in the essential oils of many aromatic plants, has in vitro and in vivo antitumor activity against several cell lines. We investigated the effects of geraniol on lipid metabolic pathways involved in Hep-G2 cell proliferation and found that geraniol inhibits the mevalonate pathway, phosphatidylcholine biosynthesis, cell growth, and cell cycle progression (with an arrest occurring at the G0/G1 interphase) and increases apoptosis. The expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting step in cholesterol synthesis, was inhibited at the transcriptional and posttranscriptional levels, as assessed by real-time RT–PCR, Western blots, and [14C]HMG-CoA-conversion radioactivity assays. That geraniol decreased cholesterogenesis but increased the incorporation of [14C]acetate into other nonsaponifiable metabolites indicated the existence of a second control point between squalene and cholesterol involved in redirecting the flow of choleste...

Research paper thumbnail of Effect of geraniol on fatty-acid and mevalonate metabolism in the human hepatoma cell line Hep G2

Biochemistry and Cell Biology, 2006

Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a d... more Monoterpenes have multiple pharmacological effects on the metabolism of mevalonate. Geraniol, a dietary monoterpene, has in vitro and in vivo anti-tumor activity against several cell lines. We have studied the effects of geraniol on growth, fatty-acid metabolism, and mevalonate metabolism in the human hepatocarcinoma cell line Hep G2. Up to 100 µmol geraniol/L inhibited the growth rate and 3-hydroxymethylglutaryl coenzyme A reductase (HMG-CoA) reductase activity of these cells. At the same concentrations, it increased the incorporation of cholesterol from the medium in a dose-dependent manner. Geraniol-treated cells incorporated less14C-acetate into nonsaponifiable lipids, inhibiting its incorporation into cholesterol but not into squalene and lanosterol. This is indicative of an inhibition in cholesterol synthesis at a step between lanosterol and cholesterol, a fact confirmed when cells were incubated with3H-mevalonate. The incorporation of3H-mevalonate into protein was also inhibi...

Research paper thumbnail of Simvastatin Effects on a Human Lung Carcinoma and Cholesterol Homeostasis of Host and Non-Host Mice

Archives Of Physiology And Biochemistry, 2001

In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor g... more In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor growth and cholesterol homeostasis of host and non-host mice, we maintained a human lung mucoepidermoid carcinoma (HLMC) in nude mice, treating these animals with Simvastatin for 33 days. The drug increased the total activity of hepatic HMG-CoA reductase without affecting the cholesterolemia. Non-treated host animals presented lower serum, tissue and microsomal hepatic cholesterol than non-host animals. These differences disappeared when animals were treated with Simvastatin, though the induction of the reductase activity at mid-dark was higher in non-host than in host animals. Simvastatin produced no significant effects on both final tumor volume and body weight. Synthesis and cholesterol homeostasis restoration induced by liver and tumoral reductase would account for no effect on the HLMC growth after a long treatment with Simvastatin.

Research paper thumbnail of Efecto sinérgico entre monoterpenos en la proliferación de células tumorales

Tercera Epoca, Dec 1, 2010

Research paper thumbnail of Aceites esenciales y su actividad antiproliferativa sobre líneas tumorales humanas

Tercera Epoca, Oct 1, 2011

Research paper thumbnail of Las gotas lípidicas nucleares constituyen un nuevo dominio nuclear

Introduccion El nucleo celular (N) es la adquisicion evolutiva que define a las celulas eucariota... more Introduccion El nucleo celular (N) es la adquisicion evolutiva que define a las celulas eucariotas, y es donde se lleva a cabo la replicacion, la transcripcion, el splicing del pre-RNAm y el ensamblaje de los ribosomas, entre otros procesos celulares. El N es una estructura altamente dinamica, formada por distintos compartimentos y dominios funcionales intranucleares que, a diferencia de los citoplasmaticos, no estan rodeados por membranas, como el nucleolo, los Cuerpos de Cajal, los compartimentos de splicing-factor (Speckles), cuerpos de “promyelocytic leucemia oncoproteins” y los cuerpos nucleares entre otros. Hemos determinado que los lipidos representan el 16% de los componentes nucleares, a su vez el 84% corresponde a fosfolipidos (PL) y el 16% a lipidos neutros. Los PL se encuentran principalmente en la envoltura nuclear mientras que los lipidos endonucleares se encuentran enriquecidos en lipidos neutros.