The metabolic advantage of tumor cells

Maurice Israël; Laurent Schwartz

doi:10.1186/1476-4598-10-70

Molecular Cancer

Table 1 Therapeutic targets

From: The metabolic advantage of tumor cells

Targets	Metabolic pathway	Activity	Drugs: inhibitors or activators	References
1	Proteolysis/alanine/transaminase/pyruvate	increased	aminooxacetic, 2PAM, D alanine, β chloro-L-alanine	[42, 43]
2	Lactate dehydrogenase/pyruvate/lactate/NAD+ Malate dehydrogenase/OAA/malate/NAD+ Malic enzyme/malate/pyruvate/lactate/NAD+	increased increased increased	Br pyruvate, gossypol D malate, humic acid D malate	[44–46]
3	Glycolysis	increased	mannoheptulose, lodinamineepalresta, citrate	[47–49]
4	PEP carboxykinase/PEP/OAA Pyruvate carboxylase/pyruvate/OAA	increased decreased	Cl-PEP, β sulphopyruvate 3-hydroxybutyrate (ketone bodies will activate)	[50, 51] [52]
5	Pyruvate kinase (M2 bottleneck)/PEP/pyruvate Pyruvate dehydrogenase/pyruvate/acetylCoA	decreased decreased	dihydroxyphenylethanol, polyethylene - glycol lipoic acid, kinase inhibitors (dichloroacetate, 2-chloropropionate) or PP2A agonists (xylulose5P, B12, choline)	[53–55] [16, 17]
6	Lipolytic fatty acid source of acetyl CoA Carnitine transporter	increased	niacine, Growth hormone inhibitors Avoid oxfenicine or levofloxacin	[56, 57]
7	Citrate synthase (OAA+ acetylCoA)/citrate	increased	Dserine, fluoroacetylCoA, carboxymethyl-CoA, citrate (via product inhibition), capsaicine (via electron transport inhibition and NADH increase)	[13]
8	ATPcitrate lyase citrate/OAA+acetylCoA Triglycerides synthesis via acetyl CoA Other OAA sources	increased increased increased	hydroxycitrate, fluorocitrate xanthohumol (removes triglycerides) D malate	[58] [59]
9	Choline dehydrogenase/methylation/lipotropic Choline kinase/phosphorylcholine/lecithin	decreased increased	choline miltefosin, farnesol	[60, 61]
10	PP2A methylation (it counteracts signaling and enzyme kinases)	decreased	betaine, folate, B12, trimethylglycine (via SAM)
11	Histone deacetylase (gene silencing)	increased	butyrate, valproate, benzamide, trichostatin	[62]
12	Cytochrome P450 demethylase (hypomethylated promoters)HAT/hexokinase expression Histone acetylase	increased increased	ketonazole, bergamottin, quinine anacardic acid, garcinol, curcumine	[63–67] [66, 67]
13	Tyrosine kinase-signaling route (MAP kin, PI3 kin, PLCγ)	increased	imatinib mésilate (glivec chemotherapy)
14,15, 16	GH-IGF IGFBP	increased decreased	octreotide, pegvisomant apigenin, casodex, omeprazol	[68–70]
17	Arginine dependency	increased	arginine deprivation diet, pegylated arginine deiminase	[18–20] [71–73]
18	Arginase/arginine/ornithine	increased	norvaline, N-omega-hydroxy-nor-arginine, boroargininre	[74–76]
19	Polyamine pathway: Ornithine decarboxylase/putrescine SAM decarboxylase	increased	DFMO (2-difluoromethylornithine), MGBG methylglyoxal bis (guanylhydrazone), 4-amidinoindan-1one-2'-amidinhydrazone(alfa-fluoromethylhistidine)	[77–79]
20	Glutaminase/glutamate	increased	DON(6-diazo-5-oxo-l-norleucine), riluzole, naftazone	[80].
21	Argininosuccinate synthetase	decreased	troglitazone	[81]

Back to article page