Departamento de Biología Celular, PharmaMar S.A., Colmenar Viejo, Madrid, Spain.
PLoS One. 2011 Apr 27;6(4):e19042. doi: 10.1371/journal.pone.0019042.
Irvalec is a marine-derived antitumor agent currently undergoing phase II clinical trials. In vitro, Irvalec induces a rapid loss of membrane integrity in tumor cells, accompanied of a significant Ca(2+) influx, perturbations of membrane conductivity, severe swelling and the formation of giant membranous vesicles. All these effects are not observed in Irvalec-resistant cells, or are significantly delayed by pretreating the cells with Zn(2+). Using fluorescent derivatives of Irvalec it was demonstrated that the compound rapidly interacts with the plasma membrane of tumor cells promoting lipid bilayer restructuration. Also, FRET experiments demonstrated that Irvalec molecules localize in the cell membrane close enough to each other as to suggest that the compound could self-organize, forming supramolecular structures that likely trigger cell death by necrosis through the disruption of membrane integrity.
Irvalec 是一种海洋来源的抗肿瘤剂，目前正在进行 II 期临床试验。在体外，Irvalec 可诱导肿瘤细胞迅速丧失膜完整性，同时伴随着显著的 Ca(2+)内流、膜电导率的改变、严重肿胀和巨大膜囊泡的形成。所有这些效应在 Irvalec 耐药细胞中均未观察到，或者在用 Zn(2+)预处理细胞后显著延迟。使用 Irvalec 的荧光衍生物证明，该化合物可迅速与肿瘤细胞膜相互作用，促进脂质双层重排。此外，FRET 实验表明，Irvalec 分子在细胞膜中彼此足够接近定位，表明该化合物可能自组装，形成超分子结构，可能通过破坏膜完整性导致细胞坏死而引发细胞死亡。
