Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/ijms22052466
Keywords
mitochondrial metabolism; Warburg effect; prostate cancer; triterpenoids
Funding
- U.S. Department of Veterans Affairs, Biomedical Laboratory Research and Development Service [5I01BX003862-02]
- J. Harold Harrison M.D. Endowment Chair
- Augusta University New Investigator Research Support funds
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Metabolic reprogramming is a hallmark of malignancy, with recent studies showing that tumor cells depend on both the Warburg effect and mitochondrial metabolism for survival. Targeting mitochondria in cancer cells is an attractive therapeutic strategy, but the metabolic flexibility of cancer cells may lead to resistance mechanisms.
Metabolic reprogramming is a hallmark of malignancy. It implements profound metabolic changes to sustain cancer cell survival and proliferation. Although the Warburg effect is a common feature of metabolic reprogramming, recent studies have revealed that tumor cells also depend on mitochondrial metabolism. Due to the essential role of mitochondria in metabolism and cell survival, targeting mitochondria in cancer cells is an attractive therapeutic strategy. However, the metabolic flexibility of cancer cells may enable the upregulation of compensatory pathways, such as glycolysis, to support cancer cell survival when mitochondrial metabolism is inhibited. Thus, compounds capable of targeting both mitochondrial metabolism and glycolysis may help overcome such resistance mechanisms. Normal prostate epithelial cells have a distinct metabolism as they use glucose to sustain physiological citrate secretion. During the transformation process, prostate cancer cells consume citrate to mainly power oxidative phosphorylation and fuel lipogenesis. A growing number of studies have assessed the impact of triterpenoids on prostate cancer metabolism, underlining their ability to hit different metabolic targets. In this review, we critically assess the metabolic transformations occurring in prostate cancer cells. We will then address the opportunities and challenges in using triterpenoids as modulators of prostate cancer cell metabolism.
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