Central de Atendimento
SP (11) 5507-2150
SP (11) 5507-2150
Artigos
Leptina, níveis e Risco de Diabetes Tipo 2 em Mulheres: Planos de pesquisas e métodos de investigaçõ...16/08/2010 11:50:51
O estudo tenta demonstrar que há uma associação forte e inversa entre níveis circulantes do receptor...
Publicações Científicas
Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the Warburg Effect30/11/2009 09:44:59
 |
Abstract Background: The unique metabolism of tumors was ... |
Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the Warburg Effect 30/11/2009 09:44:59
Abstract
Background: The unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells
with increased glycolysis and decreased mitochondrial activity. However, ‘‘aerobic glycolysis’’ generates fewer ATP per
glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how
increasing a less efficient process provides tumors with a growth advantage.
Methods/Findings: We carried out a screen for loss of genetic elements in pancreatic tumor cells that accelerated their
growth as tumors, and identified mitochondrial ribosomal protein L28 (MRPL28). Knockdown of MRPL28 in these cells
decreased mitochondrial activity, and increased glycolysis, but paradoxically, decreased cellular growth in vitro. Following
Warburg’s observations, this mutation causes decreased mitochondrial function, compensatory increase in glycolysis and
accelerated growth in vivo. Likewise, knockdown of either mitochondrial ribosomal protein L12 (MRPL12) or cytochrome
oxidase had a similar effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1) increased oxygen
consumption and decreased tumor growth. Finally, treatment of tumor bearing animals with dichloroacetate (DCA)
increased pyruvate consumption in the mitochondria, increased total oxygen consumption, increased tumor hypoxia and
slowed tumor growth.
Conclusions: We interpret these findings to show that non-oncogenic genetic changes that alter mitochondrial metabolism
can regulate tumor growth through modulation of the consumption of oxygen, which appears to be a rate limiting
substrate for tumor proliferation.
Citation: Chen Y, Cairns R, Papandreou I, Koong A, Denko NC (2009) Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the
Warburg Effect. PLoS ONE 4(9): e7033. doi:10.1371/journal.pone.0007033
Editor: Mikhail V. Blagosklonny, Roswell Park Cancer Institute, United States of America
Received July 15, 2009; Accepted August 16, 2009; Published September 15, 2009
Background: The unique metabolism of tumors was described many years ago by Otto Warburg, who identified tumor cells
with increased glycolysis and decreased mitochondrial activity. However, ‘‘aerobic glycolysis’’ generates fewer ATP per
glucose molecule than mitochondrial oxidative phosphorylation, so in terms of energy production, it is unclear how
increasing a less efficient process provides tumors with a growth advantage.
Methods/Findings: We carried out a screen for loss of genetic elements in pancreatic tumor cells that accelerated their
growth as tumors, and identified mitochondrial ribosomal protein L28 (MRPL28). Knockdown of MRPL28 in these cells
decreased mitochondrial activity, and increased glycolysis, but paradoxically, decreased cellular growth in vitro. Following
Warburg’s observations, this mutation causes decreased mitochondrial function, compensatory increase in glycolysis and
accelerated growth in vivo. Likewise, knockdown of either mitochondrial ribosomal protein L12 (MRPL12) or cytochrome
oxidase had a similar effect. Conversely, expression of the mitochondrial uncoupling protein 1 (UCP1) increased oxygen
consumption and decreased tumor growth. Finally, treatment of tumor bearing animals with dichloroacetate (DCA)
increased pyruvate consumption in the mitochondria, increased total oxygen consumption, increased tumor hypoxia and
slowed tumor growth.
Conclusions: We interpret these findings to show that non-oncogenic genetic changes that alter mitochondrial metabolism
can regulate tumor growth through modulation of the consumption of oxygen, which appears to be a rate limiting
substrate for tumor proliferation.
Citation: Chen Y, Cairns R, Papandreou I, Koong A, Denko NC (2009) Oxygen Consumption Can Regulate the Growth of Tumors, a New Perspective on the
Warburg Effect. PLoS ONE 4(9): e7033. doi:10.1371/journal.pone.0007033
Editor: Mikhail V. Blagosklonny, Roswell Park Cancer Institute, United States of America
Received July 15, 2009; Accepted August 16, 2009; Published September 15, 2009
<< Voltar
www.healthmetrix.com.br
Institucional
Exames
Profissionais da Saúde
Pacientes
Fique por dentro
Eventos
Laboratórios de Apoio
Fale Conosco
Copyright © HealthMetrix, 2009 All Rights Reserved