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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 K.-H.Park S.Jang H.J.Hwang S.-Y.Shrestha A.Lee E.-S.Kwon Y.
Ewha Authors
권영주전경화황수연
SCOPUS Author ID
권영주scopus
Issue Date
2021
Journal Title
International Journal of Molecular Sciences
ISSN
1661-6596JCR Link
Citation
International Journal of Molecular Sciences vol. 22, no. 20
Keywords
CRPCDNA intercalatorTopoisomerase II inhibitor
Publisher
MDPI
Indexed
SCIE; SCOPUS 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 topoiso-merase 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. © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.
DOI
10.3390/ijms222011246
Appears in Collections:
약학대학 > 약학과 > Journal papers
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