Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.
Medical University of Warsaw, 1 Banacha Street, 02-097 Warsaw, Poland.
Eur J Pharmacol. 2024 Sep 5;978:176751. doi: 10.1016/j.ejphar.2024.176751. Epub 2024 Jun 17.
The BM7 compound, a bromo derivative of methyl 6-acetyl-5-hydroxy-2-methyl-1-benzofuran-3-carboxylate, was previously identified as cytotoxic to human leukaemia cells (K562 and HL60) and human cervical cancer (HeLa), while showing no toxicity to non-cancerous primary endothelial cells (HUVEC). In this study, we present the first demonstration of BM7's anticancer efficacy in vivo using a mouse chronic myeloid leukaemia xenograft model. Administered intraperitoneally in a mixture of 10% Solutol HS 15/10% ethanol, BM7 exhibited no visible toxicity and significantly reduced tumor weight, comparable to standard drugs imatinib and hydroxyurea. Further supporting its anticancer potential, a multi-model in vitro study involving seven human cancer cell lines revealed the most promising responses in colon cancer (SW480, SW620, HCT116), liver cancer (HEPG2), and breast adenocarcinoma (MDA-MB-231) cells. BM7 demonstrated multifaceted anticancer mechanisms, inducing apoptosis while elevating reactive oxygen species (ROS) levels and suppressing interleukin-6 (IL-6) release in these cell lines. These findings position BM7 as a candidate of significant interest for cancer therapy. Its ability to not only induce apoptosis but also modulate cellular processes such as ROS levels and immune responses, specifically IL-6 suppression, makes BM7 a versatile and promising agent for further exploration in the realm of cancer treatment.
BM7 化合物是甲基 6-乙酰基-5-羟基-2-甲基-1-苯并呋喃-3-羧酸酯的溴代衍生物,先前被鉴定为对人白血病细胞(K562 和 HL60)和人宫颈癌(HeLa)具有细胞毒性,而对非癌细胞原代内皮细胞(HUVEC)没有毒性。在这项研究中,我们首次展示了 BM7 在体内使用小鼠慢性髓性白血病异种移植模型的抗癌功效。以 10%Solutol HS/10%乙醇混合物的形式腹腔给药,BM7 没有表现出明显的毒性,并且显著降低了肿瘤重量,与标准药物伊马替尼和羟基脲相当。进一步支持其抗癌潜力的是一项涉及七种人类癌细胞系的多模式体外研究,结果表明结肠癌(SW480、SW620、HCT116)、肝癌(HEPG2)和乳腺癌腺癌(MDA-MB-231)细胞对 BM7 的反应最有希望。BM7 表现出多方面的抗癌机制,在这些细胞系中诱导细胞凋亡,同时提高活性氧(ROS)水平并抑制白细胞介素-6(IL-6)的释放。这些发现使 BM7 成为癌症治疗的一个重要候选药物。它不仅能诱导细胞凋亡,还能调节细胞过程,如 ROS 水平和免疫反应,特别是抑制白细胞介素-6(IL-6),这使 BM7 成为癌症治疗领域进一步探索的一种多功能、有前途的药物。