PMID- 36281060 OWN - NLM STAT- MEDLINE DCOM- 20230222 LR - 20230222 IS - 1099-1573 (Electronic) IS - 0951-418X (Linking) VI - 37 IP - 2 DP - 2023 Feb TI - Juglone promotes antitumor activity against prostate cancer via suppressing glycolysis and oxidative phosphorylation. PG - 515-526 LID - 10.1002/ptr.7631 [doi] AB - 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. CI - (c) 2022 John Wiley & Sons Ltd. FAU - Hu, Cheng AU - Hu C AUID- ORCID: 0000-0003-3365-5225 AD - College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, People's Republic of China. FAU - Xu, Haiyue AU - Xu H AD - Clinical Laboratory Department, Changchun Obstetrics and Gynecology Hospital, Changchun city, Jilin, People's Republic of China. FAU - Li, Zehao AU - Li Z AD - College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, People's Republic of China. FAU - Liu, Dandan AU - Liu D AD - College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, People's Republic of China. FAU - Zhang, Siqi AU - Zhang S AD - College of medical technology, Beihua university, Jilin City, Jilin, People's Republic of China. FAU - Fang, Fang AU - Fang F AUID- ORCID: 0000-0003-0352-7847 AD - College of Laboratory Medicine, Jilin Medical University, Jilin City, Jilin, People's Republic of China. FAU - Wang, Liguo AU - Wang L AUID- ORCID: 0000-0003-4620-8838 AD - Department of Urology Surgery, Affiliated Hospital of Jilin Medical University, Jilin City, Jilin, People's Republic of China. LA - eng GR - 201913706006/Jilin Provincial Training Programs of Innovation and Entrepreneurship for Undergraduates/ GR - 202013706067/Jilin Provincial Training Programs of Innovation and Entrepreneurship for Undergraduates/ GR - JJKH20210491KJ/Science and technology research project of the Jilin Provincial Department of Education/ GR - 2020J076/hygiene and health technology innovation project of the People's Government of Jilin Province/ GR - 2020J073/hygiene and health technology innovation project of the People's Government of Jilin Province/ GR - JJKH20200460KJ/science and technology project of the 13th five year plan of the Jilin Provincial Department of Education/ PT - Journal Article DEP - 20221024 PL - England TA - Phytother Res JT - Phytotherapy research : PTR JID - 8904486 RN - W6Q80SK9L6 (juglone) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - Humans MH - Male MH - *Oxidative Phosphorylation MH - Glycolysis/physiology MH - Energy Metabolism MH - *Prostatic Neoplasms/drug therapy MH - Hexokinase/metabolism MH - Cell Line, Tumor OTO - NOTNLM OT - Warburg effect OT - glycolysis OT - juglone OT - metabolomics OT - oxidative phosphorylation OT - prostate cancer EDAT- 2022/10/26 06:00 MHDA- 2023/02/22 06:00 CRDT- 2022/10/25 00:52 PHST- 2022/08/11 00:00 [revised] PHST- 2022/03/17 00:00 [received] PHST- 2022/09/03 00:00 [accepted] PHST- 2022/10/26 06:00 [pubmed] PHST- 2023/02/22 06:00 [medline] PHST- 2022/10/25 00:52 [entrez] AID - 10.1002/ptr.7631 [doi] PST - ppublish SO - Phytother Res. 2023 Feb;37(2):515-526. doi: 10.1002/ptr.7631. Epub 2022 Oct 24.