Details

Autor(en) / Beteiligte

• Koh, Byumseok
• Ryu, Ji-Yoon
• Noh, Joseph J.
• Hwang, Jae Ryoung
• Choi, Jung-Joo
• Cho, Young-Jae
• Jang, Jiyoon
• Jo, Jeong Hyeon
• Lee, Kwangho
• Lee, Jeong-Won

Titel

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

Ist Teil von

• Gynecologic oncology, 2024-09, Vol.188, p.60-70

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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. [Display omitted] •The benzimidazole derivative BNZ-111 may be a novel treatment for ovarian cancer.•Disrupting tubulin polymerization is a mechanism of action through which BNZ-111 induces anti-cancer activity.•BNZ-111 demonstrates in vivo efficacy and potential for overcoming paclitaxel resistance.