Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system.
An efficient regulation of fuel metabolism in response to internal and environmental stimuli is a vital task that requires an intact carnitine system. The carnitine system, comprehensive of carnitine, its derivatives, and proteins involved in its transformation and transport, is indispensable for glucose and lipid metabolism in cells. Two major functions have been identified for the carnitine system: (1) to facilitate entry of long-chain fatty acids into mitochondria for their utilization in energy-generating processes; (2) to facilitate removal from mitochondria of short-chain and medium-chain fatty acids that accumulate as a result of normal and abnormal metabolism. In cancer patients, abnormalities of tumor tissue as well as nontumor tissue metabolism have been observed. Such abnormalities are supposed to contribute to deterioration of clinical status of patients, or might induce cancerogenesis by themselves. The carnitine system appears abnormally expressed both in tumor tissue, in such a way as to greatly reduce fatty acid beta-oxidation, and in nontumor tissue. In this view, the study of the carnitine system represents a tool to understand the molecular basis underlying the metabolism in normal and cancer cells. Some important anticancer drugs contribute to dysfunction of the carnitine system in nontumor tissues, which is reversed by carnitine treatment, without affecting anticancer therapeutic efficacy. In conclusion, a more complex approach to mechanisms that underlie tumor growth, which takes into account the altered metabolic pathways in cancer disease, could represent a challenge for the future of cancer research.
Peluso
G
G
Institute of Protein Biochemistry and Enzymology (I.B.P.E.) CNR, Naples, Italy. peluso@dafne.ibpe.na.cnr.it
Nicolai
R
R
Reda
E
E
Benatti
P
P
Barbarisi
A
A
Calvani
M
M
D000970:Antineoplastic Agents / Q000378:metabolism* / Q000627:therapeutic use*; D002331:Carnitine / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; D002331:Carnitine