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AK-I-190, a New Catalytic Inhibitor of Topoisomerase II with Anti-Proliferative and Pro-Apoptotic Activity on Androgen-Negative Prostate Cancer Cells
- Title
- AK-I-190, a New Catalytic Inhibitor of Topoisomerase II with Anti-Proliferative and Pro-Apoptotic Activity on Androgen-Negative Prostate Cancer Cells
- Authors
- Jeon, Kyung-Hwa; Park, Seojeong; Jang, Hae Jin; Hwang, Soo-Yeon; Shrestha, Aarajana; Lee, Eung-Seok; Kwon, Youngjoo
- Ewha Authors
- 권영주; 전경화; 황수연
- SCOPUS Author ID
- 권영주; 전경화; 황수연
- Issue Date
- 2021
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- ISSN
- 1422-0067
- Citation
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol. 22, no. 20
- Keywords
- topoisomerase II inhibitor; CRPC; DNA intercalator
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Castration-resistant prostate cancer (CRPC) is a clinical challenge in treatment because of its aggressive nature and resistance to androgen deprivation therapy. Topoisomerase II catalytic inhibitors have been suggested as a strategy to overcome these issues. We previously reported AK-I-190 as a novel topoisomerase II inhibitor. In this study, the mechanism of AK-I-190 was clarified using various types of spectroscopic and biological evaluations. AK-I-190 showed potent topoisomerase II inhibitory activity through intercalating into DNA without stabilizing the DNA-enzyme cleavage complex, resulting in significantly less DNA toxicity than etoposide, a clinically used topoisomerase II poison. AK-I-190 induced G1 arrest and effectively inhibited cell proliferation and colony formation in combination with paclitaxel in an androgen receptor-negative CRPC cell line. Our results confirmed that topoisomerase II catalytic inhibition inhibited proliferation and induced apoptosis of AR-independently growing prostate cancer cells. These findings indicate the clinical relevance of topoisomerase II catalytic inhibitors in androgen receptor-negative prostate cancer.
- DOI
- 10.3390/ijms222011246
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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