Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system

Abstract

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.

Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration

“…Anorexia is often another symptom of cachexia. The Walker 256 carcinosarcoma rat model, adopted in the present investigation, is the most studied experimental model of cancer cachexia (Peluso et al 2000) and induces most of the syndrome-correlated symptoms (Kurth et al He et al 2003;Piffar et al 2003), which are present in cancer patients (Heymsfield and McManus 1985).…”

“…Our aim was to assess whether there was correspondence with such changes and leptin synthesis by the retroperitoneal, mesenteric and epididymal WAT in Walker 256 tumour-bearing rats, a solid tumour model which induces cachexia and has been widely used in studies concerning this condition (Peluso et al 2000). During the study, we found that the adipose tissue of the tumourbearing rats was invaded by infiltrating cells.…”

Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells

“…Similarly, when palmitoylcarnitine in the presence of carnitine is provided to HT-29 cells, an increased generation of O 2 -. inside mitochondria is observed that promotes apoptosis initiation [4]. Carnitine here was proven to be a limiting factor for fatty acid import into mitochondria in colon cancer cells [1,5] with no apoptosis observed when only palmitoylcarnitine was provided to the cells [4]. In the present study, we investigated whether fl avone, beside increasing mitochondrial pyruvate or lactate transport, can increase fatty acid import into 3 101 mitochondria as a fuel for mitochondrial beta-oxidation and respiration.…”

Effects of doxorubicin-containing chemotherapy and a combination with l-carnitine on oxidative metabolism in patients with non-Hodgkin lymphoma

“…In our study we observed no influence of L-carnitine on anthracycline action-e.g., on survival times, relapse rate and major clinical parameters. This confirms previous studies indicating that carnitine treatment reverses the dysfunction of FA metabolism in nontumorous tissues of cancer patients without affecting anti-cancer therapeutic efficacy (Cruciani et al 2004;Peluso et al 2000;Sayed-Ahmed et al 2000).…”