Juglone promotes antitumor activity against prostate cancer via suppressing glycolysis and oxidative phosphorylation
Cheng Hu1, Haiyue Xu2, Zehao Li1
1College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, People's Republic of China.
Abstract:
The treatments currently used for prostate cancer (PC) do not meet clinical needs, and thus, new therapies with greater effectiveness are urgently required. Metabolic reprogramming of tumor cells is emerging as an exciting field for cancer therapy. Although the Warburg effect is a common feature of glucose metabolism in many cancers, PC cells have a unique metabolic phenotype. Non-neoplastic prostate cells show reduced oxidative phosphorylation (OXPHOS) because large, accumulated zinc inhibits citrate oxidation. During transformation, there are low levels of zinc in PC cells, and the tricarboxylic acid (TCA) cycle is reactivated. However, metastatic PC exhibits the Warburg effect. Due to metabolic differences in prostate tissue, targeting metabolic alterations in PC cells is an attractive therapeutic strategy. In this study, we investigated the effect of juglone on energy metabolism in PC cells. We found that juglone inhibited cell proliferation and induced apoptosis. Mechanistically, we demonstrated that juglone suppressed OXPHOS and glycolysis due to its inhibition of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) activity. Furthermore, downregulation of PFK and PK, but not HK contributed to the inhibition of these enzyme activities. The current study indicates that further development of juglone for PC treatment would be beneficial.
Insights
Juglone, a natural compound, effectively inhibits prostate cancer (PC) cell growth and induces apoptosis by targeting key enzymes in cellular energy metabolism, including glycolysis and oxidative phosphorylation (OXPHOS). Further research into juglone for PC treatment is warranted.
Area of Science:
- Oncology
- Cancer Metabolism
- Molecular Biology
Background:
- Prostate cancer (PC) treatments are insufficient, necessitating novel therapeutic strategies.
- Tumor metabolic reprogramming, particularly the Warburg effect and unique PC metabolic phenotypes, offers promising therapeutic targets.
- Targeting metabolic alterations in PC cells is attractive due to distinct prostate tissue metabolism.
Purpose of the Study:
- To investigate the effects of juglone on energy metabolism in prostate cancer (PC) cells.
- To elucidate the underlying mechanisms of juglone's anti-cancer activity.
- To assess the potential of juglone as a therapeutic agent for PC.
Main Methods:
- Cell proliferation assays
- Apoptosis assays
- Enzyme activity assays for hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK)
- Western blotting to assess enzyme expression levels
Main Results:
- Juglone significantly inhibited PC cell proliferation and induced apoptosis.
- Juglone suppressed both oxidative phosphorylation (OXPHOS) and glycolysis.
- Juglone's mechanism involved the inhibition of HK, PFK, and PK activities, with downregulation of PFK and PK contributing significantly.
Conclusions:
- Juglone demonstrates potent anti-cancer effects in PC cells by disrupting critical metabolic pathways.
- The inhibition of key glycolytic enzymes by juglone presents a viable therapeutic strategy.
- Juglone holds promise for further development as a novel treatment for prostate cancer.
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