Cardiolipin composition correlates with prostate cancer cell proliferation

Abstract

Prostate cancer (PC) is the second most diagnosed cancer in men. It has been recognized that diet can play a crucial role in PC genesis and progression. In this context, free fatty acids are considered as modulators of cell proliferation. Recently, a relationship between the composition of the mitochondrial phospholipid cardiolipin (CL) and cell proliferation has been discussed. The aim of this study was to analyse the interrelationship between CL composition and the proliferation of prostate cells by exposing PC-3 tumour cells to different fatty acids and by analysing the CL composition in prostate tissue from PC patients after prostatectomy. Among the applied fatty acids, palmitic acid was found to stimulate proliferation of PC-3 cells, whereas oleic acid (OA) had an inhibiting effect. The lipidomic analysis of CL revealed that fatty acids supplied to PC-3 cells were incorporated into CL molecules. Further, the CL content of palmitoleic acid (C16:1) exclusively correlated with the proliferation of PC-3 cells. The CL composition significantly differed between tumour and normal prostate tissue from PC patients. In five out of six patients, the CL content of palmitoleic acid was higher in tumour prostate tissue in comparison to normal prostate tissue. Our data illustrate that the composition of CL can be easily modified by the fatty acid environment of cells. OA was most effective in decreasing the amount of palmitoleic acid within the CL molecules and deceleration of PC-3 cell proliferation. In conclusion, a diet rich in OA might be beneficial in protecting from rapid proliferation of PC cells.

Global analysis of osteosarcoma lipidomes reveal altered lipid profiles in metastatic versus nonmetastatic cells

“…Conversely, CLs may be implicated in tumorigenesis. Indeed, CL has been found to impact prostate cancer-cell proliferation (48). Specifically, C16-rich CL was found to stimulate proliferation, and C18-rich cells were found to reduce proliferation.…”

Cardiolipins Are Biomarkers of Mitochondria-Rich Thyroid Oncocytic Tumors

“…Furthermore, redistribution of mitochondrial membrane CL and accumulation of CL oxidation products through interactions with cytochrome c are required stages in the cellular apoptotic program, a process known to occur in tumor progression (34). Recently, ox-CL were detected in PC-3 prostate cancer cell lines although their content did not correlate with the proliferation of cells (5). We have also detected ox-CL in human kidney oncocytic tumors (unpublished), further suggesting their importance in oncocytic neoplasms although more rigorous studies are needed to determine their biological role in human tumors.…”

“…Recently, HPLC-MS was used to identify CL and oxidized CL species in a rat model of traumatic brain injury (4). CL were also identified by HPLC-MS as proliferation markers in prostate cancer cell lines, and differences in CL composition were seen in tissues from six prostate cancer patients, although with no statistical significance (5). In clinical research, the ratio of the intensities of CL and monolysocardiolipins (MLCL), measured in blood by HPLC-MS, has been suggested as a screening test for Barth Syndrome (6).…”

Influence of tissue, diet, and enzymatic remodeling on cardiolipin fatty acyl profile

“…Additionally, a significant reduction in the diversity of molecular species of cardiolipin has also been reported in mouse brains affected by the presence of microgliomas [138]. In prostate tumors, cardiolipin enriched in palmitoleic acid (16:1n‐7) has been found to accelerate prostate tumor growth, and to be significantly higher in malignant tissue as compared to non‐malignant tissue . The functional relationship between cardiolipin species with increased 16:1n7 and mitochondrial function remains, however, to be determined.…”