title: Accumulation of Palmitoylcarnitine and Its Effect on Pro-Inflammatory Pathways and Calcium Influx in Prostate Cancer.
abstract: Acylcarnitines are intermediates of fatty acid oxidation and accumulate as a consequence of the metabolic dysfunction resulting from the insufficient integration between β-oxidation and the tricarboxylic acid (TCA) cycle. The aim of this study was to investigate whether acylcarnitines accumulate in prostate cancer tissue, and whether their biological actions could be similar to those of dihydrotestosterone (DHT), a structurally related compound associated with cancer development.
  
  
  
  Levels of palmitoylcarnitine (palcar), a C16:00 acylcarnitine, were measured in prostate tissue using LC-MS/MS. The effect of palcar on inflammatory cytokines and calcium (Ca(2+) ) influx was investigated in in vitro models of prostate cancer.
  
  
  
  We observed a significantly higher level of palcar in prostate cancerous tissue compared to benign tissue. High levels of palcar have been associated with increased gene expression and secretion of the pro-inflammatory cytokine IL-6 in cancerous PC3 cells, compared to normal PNT1A cells. Furthermore, we found that high levels of palcar induced a rapid Ca(2+) influx in PC3 cells, but not in DU145, BPH-1, or PNT1A cells. This pattern of Ca(2+) influx was also observed in response to DHT. Through the use of whole genome arrays we demonstrated that PNT1A cells exposed to palcar or DHT have a similar biological response.
  
  
  
  This study suggests that palcar might act as a potential mediator for prostate cancer progression through its effect on (i) pro-inflammatory pathways, (ii) Ca(2+) influx, and (iii) DHT-like effects. Further studies need to be undertaken to explore whether this class of compounds has different biological functions at physiological and pathological levels. Prostate 76:1326-1337, 2016. © 2016 The Authors. The Prostate published by Wiley Periodicals, Inc.
authors.affiliation: Department of Nutrition and Food Sciences, Al-Balqa' Applied University, Al-Salt, Jordan.
authors.forename: Ala'a
authors.initials: A
authors.lastname: Al-Bakheit
authors.affiliation: Food and Health Programme, Institute of Food Research, Norwich, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: Traka
authors.affiliation: Food and Health Programme, Institute of Food Research, Norwich, United Kingdom.
authors.forename: Shikha
authors.initials: S
authors.lastname: Saha
authors.affiliation: Food and Health Programme, Institute of Food Research, Norwich, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Mithen
authors.affiliation: Food and Health Programme, Institute of Food Research, Norwich, United Kingdom.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Melchini
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D010172:Palmitoylcarnitine / Q000032:analysis / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D010172:Palmitoylcarnitine; D002118:Calcium
keywords: acylcarnitines; dihydrotestosterone; interleukine-6 pathway; intracellular calcium signaling; metabolic disruption