1. Xanthohumol Promotes Skp2 Ubiquitination Leading to the Inhibition of Glycolysis and Tumorigenesis in Ovarian Cancer.
- Author
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He, Yi-Fu, Liu, Yi-Ping, Liao, Jin-Zhuang, Gan, Yu, Li, Xiaoying, Wang, Rui-Rui, Wang, Fang, Zhou, Jun, and Zhou, Li
- Subjects
CLINICAL drug trials ,BIOLOGICAL models ,IN vitro studies ,LEUKOCYTE count ,CARRIER proteins ,PHENOMENOLOGICAL biology ,RESEARCH funding ,ERYTHROCYTES ,PLATELET count ,T-test (Statistics) ,FLAVONOIDS ,ANTINEOPLASTIC agents ,OVARIAN tumors ,APOPTOSIS ,CELL proliferation ,HEMOGLOBINS ,ASPARTATE aminotransferase ,BIOCHEMISTRY ,BIOLOGICAL products ,XENOGRAFTS ,ENZYMES ,GLYCOPROTEINS ,IN vivo studies ,CELLULAR signal transduction ,CULTURE media (Biology) ,BLOOD urea nitrogen ,DESCRIPTIVE statistics ,QUANTITATIVE research ,HEART ,CELL lines ,MICE ,CELL culture ,IMMUNOHISTOCHEMISTRY ,GENE expression ,ANIMAL experimentation ,MOLECULAR structure ,HOSPITAL laboratories ,ALANINE aminotransferase ,ANALYSIS of variance ,CARCINOGENESIS ,CELL survival ,TRANSFERASES ,STAINS & staining (Microscopy) ,DATA analysis software ,LIVER ,WARBURG Effect (Oncology) ,IMMUNOBLOTTING ,KIDNEYS ,PHARMACODYNAMICS - Abstract
Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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