Lipids play a crucial role in the proliferation and signaling aspects of cancer cells. Thus, studying lipid alterations in prostate cancer (PCa) not only allows a better understanding of the lipidome, but can also aid in targeting the cancer more efficiently. Studies have suggested that the glycerophospholipid metabolism (GM) pathway is altered in PCa. However, the specific lipids altered in the GM pathway through variations in GM enzymes or chemotherapeutics is not fully understood. This study sought to determine the effect of LPIN1 inhibition on the lipidome and transcriptome of cells representing castration-resistant prostate cancer (CRPC) as well as the effect of docetaxel on the blood lipidome of PCa patients. The lipin family consists of three members (lipin-1, lipin-2 and lipin-3) that facilitate lipid synthesis and remodeling through the conversion of phosphatidic acid to diacylglycerol. Lipin-1 and lipin-2 are also transcriptional co-regulators. RNA sequencing and qualitative LC-MS/MS analysis of PC-3 cells with LPIN1 inhibition demonstrated alterations in the expression of numerous genes and the peak intensities of several lipids, respectively. Many of these genes and lipids aligned with pathways that mediate GM, but also focal adhesion, peroxisome proliferator-activated receptor signaling and other cellular processes. A pharmacological approach was also used to inhibit lipin in PC-3 cells using curcumin, a suggested lipin inhibitor. Curcumin decreased lipin-1 and lipin-3 expression, and had cytotoxic effects on the cells. Another important aspect not yet studied, is identifying altered lipids from PCa patients’ blood by docetaxel exposure. Docetaxel is a commonly used chemotherapeutic for the treatment of advanced PCa. However, some patients exhibit either resistance or no response to docetaxel. A qualitative LC-MS/MS analysis was performed to assess the lipidome of whole blood from PCa patients as they underwent docetaxel treatment. Several lipids were identified as key features from docetaxel exposure and associated with sphingolipid signaling and metabolism, and GM. This study also suggested identified lipids as biomarkers for docetaxel resistance in PCa. Collectively, these data suggest that LPIN1 inhibition and docetaxel exposure each exhibit significant roles in the lipidome of PCa. Personalized treatment and monitoring of PCa could be improved from these results.
