GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism
Summary: Prostate cancer (PCa) is a serious health concern for men due to its high incidence and mortality rate. The first therapy typically adopted is androgen deprivation therapy (ADT). However, patient response to ADT varies, and 20–30% of PCa cases develop into castration-resistant prostate canc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422400467X |
| _version_ | 1797291714937880576 |
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| author | Rui Wang Qi Min Yongjian Guo Yuxin Zhou Xin Zhang Dechao Wang Yuan Gao Libin Wei |
| author_facet | Rui Wang Qi Min Yongjian Guo Yuxin Zhou Xin Zhang Dechao Wang Yuan Gao Libin Wei |
| author_sort | Rui Wang |
| collection | DOAJ |
| description | Summary: Prostate cancer (PCa) is a serious health concern for men due to its high incidence and mortality rate. The first therapy typically adopted is androgen deprivation therapy (ADT). However, patient response to ADT varies, and 20–30% of PCa cases develop into castration-resistant prostate cancer (CRPC). This article investigates the anti-PCa effect of a drug candidate named GL-V9 and highlights the significant mechanism involving the AKT-hexokinase II (HKII) pathway. In both androgen receptor (AR)-expressing 22RV1 cells and AR-negative PC3 cells, GL-V9 suppressed phosphorylated AKT and mitochondrial location of HKII. This led to glycolytic inhibition and mitochondrial pathway-mediated apoptosis. Additionally, GL-V9 inhibited AR activity in 22RV1 cells and disrupted the feedback activation of AKT signaling in condition of AR inhibition. This disruption greatly increased the anti-PCa efficacy of the AR antagonist bicalutamide. In conclusion, we present a novel anti-PCa candidate and combination drug strategies to combat CRPC by intervening in the AR-AKT-HKII signaling network. |
| first_indexed | 2024-03-07T19:41:44Z |
| format | Article |
| id | doaj.art-98cc6b6b33564ab7a7e0f8677841d4ed |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-07T19:41:44Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-98cc6b6b33564ab7a7e0f8677841d4ed2024-02-29T05:20:18ZengElsevieriScience2589-00422024-03-01273109246GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanismRui Wang0Qi Min1Yongjian Guo2Yuxin Zhou3Xin Zhang4Dechao Wang5Yuan Gao6Libin Wei7Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of ChinaNanjing University of Chinese Medicine, 138 Xianlin Rd, Nanjing 210023, the People’s Republic of China; Department of Oncology, Huai’an Second People’s Hospital, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huaian, the People’s Republic of ChinaJiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of ChinaJiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of ChinaJiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of ChinaJiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of ChinaPharmaceutical Animal Experiment Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of China; Corresponding authorJiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, the People’s Republic of China; Corresponding authorSummary: Prostate cancer (PCa) is a serious health concern for men due to its high incidence and mortality rate. The first therapy typically adopted is androgen deprivation therapy (ADT). However, patient response to ADT varies, and 20–30% of PCa cases develop into castration-resistant prostate cancer (CRPC). This article investigates the anti-PCa effect of a drug candidate named GL-V9 and highlights the significant mechanism involving the AKT-hexokinase II (HKII) pathway. In both androgen receptor (AR)-expressing 22RV1 cells and AR-negative PC3 cells, GL-V9 suppressed phosphorylated AKT and mitochondrial location of HKII. This led to glycolytic inhibition and mitochondrial pathway-mediated apoptosis. Additionally, GL-V9 inhibited AR activity in 22RV1 cells and disrupted the feedback activation of AKT signaling in condition of AR inhibition. This disruption greatly increased the anti-PCa efficacy of the AR antagonist bicalutamide. In conclusion, we present a novel anti-PCa candidate and combination drug strategies to combat CRPC by intervening in the AR-AKT-HKII signaling network.http://www.sciencedirect.com/science/article/pii/S258900422400467XClassification DescriptionMolecular biologyCell biologyCancer |
| spellingShingle | Rui Wang Qi Min Yongjian Guo Yuxin Zhou Xin Zhang Dechao Wang Yuan Gao Libin Wei GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism iScience Classification Description Molecular biology Cell biology Cancer |
| title | GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism |
| title_full | GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism |
| title_fullStr | GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism |
| title_full_unstemmed | GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism |
| title_short | GL-V9 inhibits the activation of AR-AKT-HK2 signaling networks and induces prostate cancer cell apoptosis through mitochondria-mediated mechanism |
| title_sort | gl v9 inhibits the activation of ar akt hk2 signaling networks and induces prostate cancer cell apoptosis through mitochondria mediated mechanism |
| topic | Classification Description Molecular biology Cell biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S258900422400467X |
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