Emd-D inhibited ovarian cancer progression via PFKFB4-dependent glycolysis and apoptosis.
10.1016/S1875-5364(25)60843-0
- Author:
Xin ZHAO
1
;
Chao CHEN
2
;
Xuefei FENG
2
;
Haoqi LEI
2
;
Lingling QI
2
;
Hongxia ZHANG
2
;
Haiying XU
2
;
Jufeng WAN
2
;
Yan ZHANG
3
;
Baofeng YANG
4
Author Information
1. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin 150081, China.
2. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China.
3. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin 150081, China. Electronic address: zhangyan@ems.hrbmu.edu.cn.
4. Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150081, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases (NKLFZCD), Harbin Medical University, Harbin 150081, China; Research Unit of Noninfectious Chronic Diseases in Frigid Zone (2019RU070), Chinese Academy of Medical Sciences, Harbin 150081, China. Electronic address: yangbf@ems.hrbmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Emd-D;
Glycolysis;
Ovarian cancer;
PFKFB4
- MeSH:
Female;
Humans;
Ovarian Neoplasms/physiopathology*;
Phosphofructokinase-2/genetics*;
Apoptosis/drug effects*;
Glycolysis/drug effects*;
Animals;
Cell Line, Tumor;
Mice;
Cell Proliferation/drug effects*;
Emodin/administration & dosage*;
Mice, Nude;
Mice, Inbred BALB C;
Hexokinase/metabolism*;
Xenograft Model Antitumor Assays
- From:
Chinese Journal of Natural Medicines (English Ed.)
2025;23(4):431-442
- CountryChina
- Language:English
-
Abstract:
Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
