Trabectedin (Ecteinascidin 743) has potent antitumor activity and the potential for soft tissue sarcoma and ovarian cancer research. Trabectedin inhibits cell growth of MX-1, MCF7 and MCF7/DXR cells with IC50 values of 0.1 nM, 1.5 nM and 3.7 nM, respectively.

ROS:0.1 nM(MX-1 cells), ROS:1.5 nM(MCF7 cells), ROS:3.7 nM(MCF7/DXR cells)

In MCF7 cells, Trabectedin (10 nM; 24-72 hours) results in cell accumulation in late S to G2 phase[1]. Trabectedin induces cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. In MDA-MB-453 cells, the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions are induced by 4.2-, 3.6-, 4.8-, 4.5-, and 4.4-fold, and the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL are reduced by 4.8- and 5.2-fold. In MCF-7 cells, the expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, and FADD are significantly increased by 2.6-, 3.1-, 1.7-, 11.2- and 4.0-fold by Trabectedin treatment[2]. Trabectedin selectively inhibits the production of CCL2, CXCL8, IL-6, VEGF, and PTX3 by myxoid liposarcoma (MLS) primary tumor cultures and/or cell lines[3].

In female athymic nude mice, Trabectedin (30-50 μg/kg; intravenous injection; every three days) increased the antitumor effects in nude mice bearing MX-1 mammary carcinoma xenografts without increasing toxicity[1]. In a xenograft mouse model of human myxoid liposarcoma (MLS), Trabectedin reduced CCL2, CXCL8, CD68+ infiltrating macrophages, CD31+ tumor vessels, and partial decreased PTX3[3].