Biological activity of palmitoylcarnitine in prostate cancer

Acylcarnitines are intermediates of fatty acid oxidation and accumulate as a result of a metabolic defect. Accumulation of palmitoylcarnitine (palcar), a long-chain acylcarnitine, has been observed in diabetes mellitus type II, obesity and kidney cancer. Certain dietary intervention studies have been shown to reduce serum and urinary levels of acylcarnitines. It was shown that palcar accumulates in prostate cancer tissue, possibly indicative of the metabolic changes associated with cancer development, but that palcar at high concentrations may have activities that could be associated with cancer development. Through the use of cancerous (PC3, DU145) and non-cancerous (PNT1A, BPH) cell models, it was shown that high levels of palcar could induce gene expression of the inflammatory cytokine IL-6, and induce its secretion in PC3 cells. This was associated with the rapid influx of Ca2+. Through the use of various metabolic inhibitors, it was shown that Ca2+ influx includes the activation of G-protein coupled receptors, L-type Ca2+ channels and PI3K pathway. However, it was shown through the use of global gene arrays that lower levels of palcar with uncorrected P value induced many changes in gene expression in PNT1A cells. A comparison with the global changes induced by DHT, an androgen linked to prostate cancer progression, revealed a significant overlap in activity between palcar and DHT, suggesting that palcar may have a potential role in promoting cancer progression. In PC3 cells through the use of real time RT-PCR palcar was shown to induce glycolysis. In conclusion, it is suggested that palcar may represent a potential biomarker of the metabolic dysfunction associated with prostate cancer. At physiological levels palcar had no effects on the prostate cancer cells, however, at high levels palcar drive tumour development through inducing key inflammatory cytokine and inducing changes in gene expression associated with glycolysis.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2014

Author dc:creator

• Al-Bakheit, Alaa

Language dc:language

en