Francesconi Oscar, Corzana Francisco, Kontogianni Georgia-Ioanna, Pesciullesi Giorgio, Gualdani Roberta, Supuran Claudiu T, Angeli Andrea, Kavasi Rafaela Maria, Chatzinikolaidou Maria, Nativi Cristina
Department of Chemistry, DICUS, University of Florence, via della Lastruccia, 3-13, Sesto Fiorentino, 50019Florence, Italy.
Departamento de Química, Centro de Investigación en Síntesis Química, Universidad de La Rioja, 26006Logroño, Spain.
ACS Pharmacol Transl Sci. 2022 Sep 13;5(11):1119-1127. doi: 10.1021/acsptsci.2c00114. eCollection 2022 Nov 11.
Osteosarcoma is a heterogeneous tumor intimately linked to its microenvironment, which promotes its growth and spread. It is generally accompanied by cancer-induced bone pain (CIBP), whose main component is neuropathic pain. The TRPA1 ion channel plays a key role in metastasis and is increasingly expressed in bone cancer. Here, a novel TRPA1 inhibitor is described and tested together with two other known TRPA1 antagonists. The novel lipoyl derivative has been successfully assessed for its ability to reduce human osteosarcoma MG-63 cell viability, motility, and gene expression of the CIBP pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A putative three-dimensional (3D) model of the inhibitor covalently bound to TRPA1 is also proposed. The in vitro data suggest that the novel inhibitor described here may be highly interesting and stimulating for new strategies to treat osteosarcomas.
骨肉瘤是一种与其微环境密切相关的异质性肿瘤，微环境促进其生长和扩散。它通常伴有癌症诱导的骨痛（CIBP），其主要成分是神经性疼痛。TRPA1离子通道在转移中起关键作用，并且在骨癌中表达增加。在此，描述了一种新型TRPA1抑制剂，并与其他两种已知的TRPA1拮抗剂一起进行测试。已成功评估了这种新型脂酰衍生物降低人骨肉瘤MG-63细胞活力、运动能力以及CIBP促炎细胞因子白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）基因表达的能力。还提出了抑制剂与TRPA1共价结合的三维（3D）模型推测。体外数据表明，本文所述的新型抑制剂可能对治疗骨肉瘤的新策略极具吸引力并具有启发性。
