Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway
The Polycomb protein enhancer of zeste homolog 2 (EZH2) has critical roles in prostate cancer (PCa) progression and drug-resistance, which remains an obstacle for PCa treatment. Enzalutamide (ENZ) is a second-generation androgen receptor antagonist employed for treatment of metastatic castration-res...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.723729/full |
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| author | Lang Guo Xiaowei Luo Ping Yang Yanting Zhang Jialuo Huang Hong Wang Yinfeng Guo Weifeng Huang Zhiqiang Chen Shusheng Wang Junjian Wang Jinping Lei Songtao Xiang Yonghong Liu Yonghong Liu |
| author_facet | Lang Guo Xiaowei Luo Ping Yang Yanting Zhang Jialuo Huang Hong Wang Yinfeng Guo Weifeng Huang Zhiqiang Chen Shusheng Wang Junjian Wang Jinping Lei Songtao Xiang Yonghong Liu Yonghong Liu |
| author_sort | Lang Guo |
| collection | DOAJ |
| description | The Polycomb protein enhancer of zeste homolog 2 (EZH2) has critical roles in prostate cancer (PCa) progression and drug-resistance, which remains an obstacle for PCa treatment. Enzalutamide (ENZ) is a second-generation androgen receptor antagonist employed for treatment of metastatic castration-resistant prostate cancer A considerable proportion of tumors eventually develop resistance during treatment. Thus, agents that can overcome resistance to PCa are needed urgently. Ilicicolin A (Ili-A), an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, shows antiproliferative activity in human PCa cells, but its mechanism of action against Castration-resistant prostate cancer is not known. Herein, RNA-sequencing showed the EZH2 pathway to be involved in PCa proliferation. Ili-A at low doses reduced the protein level of EZH2, leading to transcriptional change. Interestingly, Ili-A suppressed the binding of EZH2 to promoter regions in AR/serine/threonine polo-like kinase-1/aurora kinase A. Moreover, Ili-A could enhance the anticancer activity of enzalutamide in CRPC cancer models. These data suggest that Ili-A could be used in combination with enzalutamide to treat CRPC. |
| first_indexed | 2024-12-21T07:01:31Z |
| format | Article |
| id | doaj.art-f1278381bae242628e1309588b1bab8e |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T07:01:31Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f1278381bae242628e1309588b1bab8e2022-12-21T19:12:12ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-10-011210.3389/fphar.2021.723729723729Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling PathwayLang Guo0Xiaowei Luo1Ping Yang2Yanting Zhang3Jialuo Huang4Hong Wang5Yinfeng Guo6Weifeng Huang7Zhiqiang Chen8Shusheng Wang9Junjian Wang10Jinping Lei11Songtao Xiang12Yonghong Liu13Yonghong Liu14Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInstitute of Marine Drugs/Guangxi Key Laboratory of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, ChinaDepartment of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaInstitute of Marine Drugs/Guangxi Key Laboratory of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaDepartment of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaInstitute of Marine Drugs/Guangxi Key Laboratory of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, ChinaCAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, ChinaThe Polycomb protein enhancer of zeste homolog 2 (EZH2) has critical roles in prostate cancer (PCa) progression and drug-resistance, which remains an obstacle for PCa treatment. Enzalutamide (ENZ) is a second-generation androgen receptor antagonist employed for treatment of metastatic castration-resistant prostate cancer A considerable proportion of tumors eventually develop resistance during treatment. Thus, agents that can overcome resistance to PCa are needed urgently. Ilicicolin A (Ili-A), an ascochlorin derivative isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, shows antiproliferative activity in human PCa cells, but its mechanism of action against Castration-resistant prostate cancer is not known. Herein, RNA-sequencing showed the EZH2 pathway to be involved in PCa proliferation. Ili-A at low doses reduced the protein level of EZH2, leading to transcriptional change. Interestingly, Ili-A suppressed the binding of EZH2 to promoter regions in AR/serine/threonine polo-like kinase-1/aurora kinase A. Moreover, Ili-A could enhance the anticancer activity of enzalutamide in CRPC cancer models. These data suggest that Ili-A could be used in combination with enzalutamide to treat CRPC.https://www.frontiersin.org/articles/10.3389/fphar.2021.723729/fullascochlorin derivativesenhancer of zeste homolog 2enzalutamidecastration-resistant prostate cancer (CRPC)androgen receptor |
| spellingShingle | Lang Guo Xiaowei Luo Ping Yang Yanting Zhang Jialuo Huang Hong Wang Yinfeng Guo Weifeng Huang Zhiqiang Chen Shusheng Wang Junjian Wang Jinping Lei Songtao Xiang Yonghong Liu Yonghong Liu Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway Frontiers in Pharmacology ascochlorin derivatives enhancer of zeste homolog 2 enzalutamide castration-resistant prostate cancer (CRPC) androgen receptor |
| title | Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway |
| title_full | Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway |
| title_fullStr | Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway |
| title_full_unstemmed | Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway |
| title_short | Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway |
| title_sort | ilicicolin a exerts antitumor effect in castration resistant prostate cancer via suppressing ezh2 signaling pathway |
| topic | ascochlorin derivatives enhancer of zeste homolog 2 enzalutamide castration-resistant prostate cancer (CRPC) androgen receptor |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.723729/full |
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