Prostate cancer cells elevate glycolysis and G6PD in response to caffeic acid phenethyl ester-induced growth inhibition

作     者：Lin, Tzu-Ping Chen, Pei-Chun Lin, Ching-Yu Wang, Bi-Juan Kuo, Ying-Yu Yeh, Chien-Chih Tseng, Jen-Chih Huo, Chieh Kao, Cheng-Li Shih, Li-Jane Chen, Jen-Kun Li, Chia-Yang Hour, Tzyh-Chyuan Chuu, Chih-Pin 

作者机构：Natl Yang Ming Chiao Tung Univ Inst Electroopt Engn Hsinchu 30010 Taiwan Taipei Vet Gen Hosp Dept Urol Taipei City 11217 Taiwan Natl Hlth Res Inst Inst Cellular & Syst Med Zhunan 35053 Miaoli County Taiwan Taipei Med Univ Ph D Program Canc Mol Biol & Drug Discovery Taipei City Taiwan Taoyuan Armed Forces Gen Hosp Dept Internal Med Taoyuan City 325208 Taiwan Triserv Gen Hosp Natl Def Med Ctr Dept Surg Div Colon & Rectal Surg Taipei City 114202 Taiwan Natl Hlth Res Inst Immunol Res Ctr Zhunan Miaoli Taiwan Triserv Gen Hosp Natl Def Med Ctr Dept Obstet & Gynecol Taipei City 114202 Taiwan Armed Forces Taoyuan Gen Hosp Dept Surg Div Urol Taoyuan Taiwan Natl Def Med Ctr Grad Inst Med Sci Taipei City 114202 Taiwan Natl Hlth Res Inst Inst Biomed Engn & Nanomed Zhunan 35053 Miaoli Taiwan Kaohsiung Med Univ Grad Inst Med Coll Med Kaohsiung 80708 Taiwan Kaohsiung Med Univ Hosp Dept Med Res Kaohsiung 80708 Taiwan Kaohsiung Med Univ Neurosci Res Ctr Kaohsiung 80708 Taiwan Kaohsiung Med Univ Coll Med Dept Biochem Kaohsiung 80708 Taiwan Kaohsiung Med Univ Hosp Dept Med Res Kaohsiung 80708 Taiwan China Med Univ PhD Program Aging Taichung 40402 Taiwan Natl Chung Hsing Univ Biotechnol Ctr Taichung 40227 Taiwan Natl Cent Univ Dept Life Sci Taoyuan City 320317 Taiwan 

出 版 物：《BMC CANCER》 (BMC Cancer)

年 卷 期：2025年第25卷第1期

页      面：1-12页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Taoyuan Armed Forces General Hospital 

主　　题：Caffeic acid phenethyl ester Prostate cancer Glycolysis G6PD Pyruvate Lactate 

摘      要：BackgroundCaffeic acid phenethyl ester (CAPE) is the main bioactive component of poplar type propolis. We previously reported that treatment with caffeic acid phenethyl ester (CAPE) suppressed the cell proliferation, tumor growth, as well as migration and invasion of prostate cancer (PCa) cells via inhibition of signaling pathways of AKT, c-Myc, Wnt and EGFR. We also demonstrated that combined treatment of CAPE and docetaxel altered the genes involved in glycolysis and tricarboxylic acid (TCA) cycle. We therefore suspect that CAPE treatment may interfere glucose metabolism in PCa *** Bioenergetics platform was applied to analyzed the extra cellular acidification rate (ECAR) and oxygen consumption rate (OCR) of PCa cells under CAPE treatment. UPLC-MSMS with Multiple Reaction Monitoring (MRM), PCR, and western blot were used to analyze the effects of CAPE on metabolites, genes, and proteins involved in glycolysis, TCA cycle and pentose phosphate pathway in PCa cells. Flow cytometry and ELISA were used to determine the level of reactive oxygen species in PCa cells being treated with *** Bioenergetics analysis revealed that ECAR, glycolysis, OCR, and ATP production were elevated in C4-2B cells under CAPE treatment. Protein levels of glucose-6-phosphate dehydrogenase (G6PD), phosphogluconate dehydrogenase (PGD), glutaminase (GLS), phospho-AMPK Thr172 as well as abundance of pyruvate, lactate, ribulose-5-phosphate, and sedoheptulose-7-phosphate were increased in CAPE-treated C4-2B cells. ROS level decreased 48 h after treatment with CAPE. Co-treatment of AMPK inhibitor with CAPE exhibited additive growth inhibition on PCa *** study indicated that PCa cells attempted to overcome the CAPE-induced stress by upregulation of glycolysis and G6PD but failed to impede the growth inhibition caused by CAPE. Concurrent treatment of CAPE and inhibitors targeting glycolysis may be effective therapy for advanced PCa.