2. Academic Validation
  3. Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway

Ilicicolin A Exerts Antitumor Effect in Castration-Resistant Prostate Cancer Via Suppressing EZH2 Signaling Pathway

  • Front Pharmacol. 2021 Oct 27:12:723729. doi: 10.3389/fphar.2021.723729.
Lang Guo 1,  Xiaowei Luo 2,  Ping Yang 3,  Yanting Zhang 2,  Jialuo Huang 4,  Hong Wang 4,  Yinfeng Guo 4,  Weifeng Huang 4,  Zhiqiang Chen 1,  Shusheng Wang 1,  Junjian Wang 5,  Jinping Lei 4,  Songtao Xiang 1,  Yonghong Liu 2 6
Affiliations

Affiliations

  • 1 Department of Urology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 2 Institute of Marine Drugs/Guangxi Key Laboratory of Marine Drugs, Guangxi University of Chinese Medicine, Nanning, China.
  • 3 Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
  • 4 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
  • 5 Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
  • 6 CAS 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, China.
PMID: 34776951 DOI: 10.3389/fphar.2021.723729
Abstract

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.

Keywords

androgen receptor; ascochlorin derivatives; castration-resistant prostate cancer (CRPC); enhancer of zeste homolog 2; enzalutamide.

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