How does the metabolism of tumour cells differ from that of normal cells.
Tumour cells thrive in environments that would be hostile to their normal cell counterparts. Survival depends on the selection of cell lines that harbour modifications of both, gene regulation that shifts the balance between the cell cycle and apoptosis and those that involve the plasticity of the metabolic machinery. With regards to metabolism, the selected phenotypes usually display enhanced anaerobic glycolysis even in the presence of oxygen, the so-called Warburg effect, and anabolic pathways that provide precursors for the synthesis of lipids, proteins and DNA. The review will discuss the original ideas of Otto Warburg and how they initially led to the notion that mitochondria of tumour cells were dysfunctional. Data will be presented to show that not only the organelles are viable and respiring, but that they are key players in tumorigenesis and metastasis. Likewise, interconnecting pathways that stand out in the tumour phenotype and that require intact mitochondria such as glutaminolysis will be addressed. Furthermore, comments will be made as to how the peculiarities of the biochemistry of tumour cells renders them amenable to new forms of treatment by highlighting possible targets for inhibitors. In this respect, a case study describing the effect of a metabolite analogue, the alkylating agent 3BP (3-bromopyruvate), on glycolytic enzyme targets will be presented.
*Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Av, Carlos Chagas Filho 373, Ilha do Fundão CEP 21941-590, Rio de Janeiro, Brazil.
Nívea Dias
ND
Amoêdo
*Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Av, Carlos Chagas Filho 373, Ilha do Fundão CEP 21941-590, Rio de Janeiro, Brazil.
Juan Perez
JP
Valencia
*Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Av, Carlos Chagas Filho 373, Ilha do Fundão CEP 21941-590, Rio de Janeiro, Brazil.
Mariana Figueiredo
MF
Rodrigues
*Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Av, Carlos Chagas Filho 373, Ilha do Fundão CEP 21941-590, Rio de Janeiro, Brazil.
Antonio
A
Galina
*Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Av, Carlos Chagas Filho 373, Ilha do Fundão CEP 21941-590, Rio de Janeiro, Brazil.
Franklin David
FD
Rumjanek
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D005973:Glutamine / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
D000970:Antineoplastic Agents; D005973:Glutamine