Abstract
Metabolic reprogramming plays a crucial role in the development of cancer. The aim of this study was to explore the effect of fenofibrate, an agonist of peroxisome proliferator-activated receptor alpha (PPARα), on gene expression profiles of mitochondrial energy metabolism. Our results showed that PPARα expression was negatively correlated with tumor progression in an oral cancer mouse model. Activation of PPARα through fenofibrate suppressed migration of oral cancer cells. Differential protein profiling demonstrated that expressions of genes related to mitochondrial energy metabolism were either up-regulated (Atp5g3, Cyc1, Ndufa5, Ndufa10, and Sdhd) or down-regulated (Cox5b, Ndufa1, Ndufb7, and Uqcrh) through PPARα activation and response. Our results indicate that PPARα exhibits a great potential for anti-oral cancer therapies by modulating cancer cell mitochondrial energy metabolism.
Highlights
One of the prominent characteristics of rapidly growing cancer cells is their capacity to sustain high rates of glycolysis for ATP production regardless of whether oxygen is present—a phenomenon known as the Warburg effect [1]
The PPARα protein levels were progressively decreased in a time-dependent manner over a 28-week observation period when compared with the control (0 week)
Linear regression analysis showed that PPARα expression was negatively correlated with the advancing of tumor development (P = 0.003)
Summary
One of the prominent characteristics of rapidly growing cancer cells is their capacity to sustain high rates of glycolysis for ATP production regardless of whether oxygen is present—a phenomenon known as the Warburg effect [1]. Activators of peroxisome proliferator-activated receptors (PPARs) have been shown to exhibit a great potential for anticancer therapies by modulating cancer cell energy metabolism and signaling pathways [2, 3]. Fenofibrate has been reported to be involved in several anticancer activities, including induction of apoptosis, reduction of the proliferation rate, attenuation of IGF-1 receptor signaling, inhibition of tumor angiogenesis, and suppression of the inflammatory response and oxidative stress in cancer cells like melanoma, mantle cell lymphoma, medulloblastoma, glioma, and endometrial cancer cells [8,9,10,11,12,13,14]. The anticancer activity of fenofibrate in energy homeostasis is not well clarified or understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
