Anti-cancer effects of benzimidazole derivative BNZ-111 on paclitaxel-resistant ovarian cancer.

Autor: Koh B; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Medicinal Chemistry & Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea., Ryu JY; Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea., Noh JJ; Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea., Hwang JR; Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea., Choi JJ; Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea., Cho YJ; Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea., Jang J; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea., Jo JH; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon 34134, Republic of Korea., Lee K; Bio and Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Medicinal Chemistry & Pharmacology, University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address: kwangho@krict.re.kr., Lee JW; Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. Electronic address: garden.lee@samsung.com.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Sep; Vol. 188, pp. 60-70. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.1016/j.ygyno.2024.06.011
Abstrakt: Objective: Ovarian cancer, a leading cause of cancer-related deaths in women, remains a formidable challenge, especially in the context of platinum-resistant disease. This study investigated the potential of the benzimidazole derivative BNZ-111 as a novel treatment strategy for platinum-resistant ovarian cancer.
Methods: The human EOC cell lines A2780, HeyA8, SKOV3ip1, A2780-CP20, HeyA8-MDR, and SKOV3-TR were treated with BNZ-111, and cell proliferation, apoptosis, and cell cycle were assessed.
Results: It demonstrated strong cytotoxicity in both chemo-sensitive and chemo-resistant epithelial ovarian cancer cell lines, inducing apoptosis and G2/M cell cycle arrest. In vivo experiments using orthotopic and patient-derived xenograft models showed significant tumor growth inhibition without apparent toxicity to vital organs. Unlike paclitaxel, BNZ-111 proved effective in paclitaxel-resistant cells, potentially by bypassing interaction with MDR1 and modulating β-3 tubulin expression to suppress microtubule dynamics.
Conclusion: BNZ-111, with favorable drug-like properties, holds promise as a therapeutic option for platinum-resistant ovarian cancer, addressing a critical clinical need in gynecologic oncology.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that they have no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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