{"doi":"10.1002/pros.24336","title":"Diptoindonesin G antagonizes AR signaling and enhances the efficacy of antiandrogen therapy in prostate cancer","abstract":"BACKGROUND: The androgen receptor (AR) signaling pathway has been well demonstrated to play a crucial role in the development, progression, and drug resistance of prostate cancer. Although the current anti-androgen therapy could significantly benefit prostate cancer patients initially, the efficacy of the single drug usually lasts for a relatively short period, as drug resistance quickly emerges. METHODS: We have performed an unbiased bioinformatics analysis using the RNA-seq results in 22Rv1 cells to identify the cell response toward Dip G treatment. The RNA-seq results were validated by qRT-PCR. Protein levels were detected by western blot or staining. Cell viability was measured by Aquabluer and colony formation assay. RESULTS: Here, we identified that Diptoindonesin G (Dip G), a natural extracted compound, could promote the proteasome degradation of AR and polo-like kinase 1 (PLK1) through modulating the activation of CHIP E3 ligase. Administration of Dip G has shown a profound efficiency in the suppression of AR and PLK1, not only in androgen-dependent LNCaP cells but also in castration-resistant and enzalutamide-resistant cells in a CHIP-dependent manner. Through co-targeting the AR signaling, Dip G robustly improved the efficacy of HSP90 inhibitors and enzalutamide in both human prostate cancer cells and in vivo xenograft mouse model. CONCLUSIONS: Our results revealed that Dip G-mediated AR degradation would be a promising and valuable therapeutic strategy in the clinic.","journal":"The Prostate","year":2022,"id":294205,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":411938,"name":"Yifan Kong","orcid":"0000-0002-5650-8079","position":1,"is_corresponding":false},{"id":411941,"name":"Jinghui Liu","orcid":"0000-0002-9676-1538","position":2,"is_corresponding":false},{"id":979200,"name":"Xiongjian Rao","orcid":"0000-0001-5645-9994","position":3,"is_corresponding":false},{"id":411937,"name":"Chaohao Li","orcid":"0000-0001-5975-3937","position":4,"is_corresponding":false},{"id":651461,"name":"Kristine Donahue","orcid":"0000-0003-3248-7573","position":5,"is_corresponding":false},{"id":411940,"name":"Yanquan Zhang","orcid":"0000-0003-3527-9972","position":6,"is_corresponding":false},{"id":730677,"name":"Katelyn Jones","orcid":null,"position":7,"is_corresponding":false},{"id":747532,"name":"Qiongsi Zhang","orcid":"0000-0002-6234-5034","position":8,"is_corresponding":false},{"id":579437,"name":"Wei Xu","orcid":"0000-0003-3808-0045","position":9,"is_corresponding":false},{"id":411943,"name":"Xiaoqi Liu","orcid":"0000-0002-6613-1746","position":10,"is_corresponding":false},{"id":411939,"name":"Fengyi Mao","orcid":"0000-0001-7785-6606","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:30:57.469517Z","pmid":"35322879","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}