{"title":"Selective killing of castration-resistant prostate cancer cells by formycin A via the ATF4–CHOP axis","authors":"Tomoki Takei, Yuki Hamamura, Hiroshi Hongo, Etsu Tashiro, Masaya Imoto, Takeo Kosaka, Mototsugu Oya","doi":"10.1111/cas.16349","DOIUrl":null,"url":null,"abstract":"<p>Prostate cancer is initially androgen-dependent but often relapses to an androgen-independent state called castration-resistant prostate cancer (CRPC). Currently approved therapies have limited efficacy against CRPC, highlighting the need for novel therapeutic strategies. To address this need, we conducted a drug screen in our previously established aggressive CRPC cell model. We found that formycin A induced cell death in CRPC model cells but not in parental prostate cancer cells. In addition, formycin A upregulated death receptor 5 through the induction of endoplasmic reticulum stress, activating the “extrinsic” apoptosis pathway in CRPC model cells. Moreover, formycin A showed in vivo antitumor efficacy against CRPC xenografts in castrated nude mice. Thus, our findings highlight the potential of formycin A as a CRPC therapeutic.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 12","pages":"3997-4007"},"PeriodicalIF":4.5000,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.16349","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cas.16349","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Prostate cancer is initially androgen-dependent but often relapses to an androgen-independent state called castration-resistant prostate cancer (CRPC). Currently approved therapies have limited efficacy against CRPC, highlighting the need for novel therapeutic strategies. To address this need, we conducted a drug screen in our previously established aggressive CRPC cell model. We found that formycin A induced cell death in CRPC model cells but not in parental prostate cancer cells. In addition, formycin A upregulated death receptor 5 through the induction of endoplasmic reticulum stress, activating the “extrinsic” apoptosis pathway in CRPC model cells. Moreover, formycin A showed in vivo antitumor efficacy against CRPC xenografts in castrated nude mice. Thus, our findings highlight the potential of formycin A as a CRPC therapeutic.
期刊介绍：
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.
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