Apoptosis is a form of programmed cell death in multicellular organisms. Specifically, apoptotic signals help to protect genomic integrity, and defective apoptosis may promote carcinogenesis. Inflammatory mediators present in the tumor environment may promote cancer progression and are promising targets for new biotherapy. Besides, the small groove of double helix B-DNA has become an important part of the development of new drugs. Because it is the site of non-covalent high sequence-specific interaction of a large number of small molecules. Small groove binders are characterized by a high level of sequence specificity. Moreover, they are still an interesting class of DNA ligands. DNA groove binders constitute an important class of derivatives in anticancer therapy.

Furthermore, DNA damage is recognized as a key factor in cancer development and progression. DNA damage can produce abnormal nucleotides or nucleotide fragments, resulting in one or two-strand breaks of the DNA chain. Meanwhile, DNA damage can change the nucleotide sequence and lead to the expression of dysfunctional proteins affecting normal cell physiology. Here, we will introduce a tetrahydroisoquinoline alkaloid with potent antitumor activity, Trabectedin (Ecteinascidin 743).

Trabectedin (Ecteinascidin 743) is a Tetrahydroisoquinoline Alkaloid with Antitumor Activity.

At first, Trabectedin (Ecteinascidin 743) is a tetrahydroisoquinoline alkaloid with potent antitumor activity. Nonetheless, Trabectedin binds to the minor groove of DNA, blocks transcription of stress-induced proteins. Trabectedin induces DNA backbone cleavage and cancer cells apoptosis and increases the generation of ROS in MCF-7 and MDA-MB-453 cells. Importantly, Trabectedin has the potential for soft tissue sarcoma and ovarian cancer research.

Secondly, Trabectedin with 10 nM for 24-72 hours causes cells to accumulate in the late S to G2 phase. Particularly, 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. Trabectedin induces cytotoxicity and apoptosis in both breast cancer cells in a time and concentration-dependent manner. Trabectedin significantly increased the expression levels of the death receptor pathway molecules, TRAIL-R1/DR4, TRAIL-R2/DR5, FAS/TNFRSF6, TNF RI/TNFRSF1A, FADD in MCF-7 cells. In MDA-MB-453 cells, Trabectedin induced the mitochondrial pathway related pro-apoptotic proteins Bax, Bad, Cytochrome c, Smac/DIABLO, and Cleaved Caspase-3 expressions. Obviously, it reduced the expression levels of anti-apoptotic proteins Bcl-2 and Bcl-XL in MDA-MB-453 cells.

Thirdly, Trabectedin with 30-50 μg/kg by iv every three days increases the antitumor effects in nude mice bearing MX-1 mammary carcinoma xenografts. Additionally, it is without increasing toxicity. Trabectedin reduces CCL2, CXCL8, CD68+ infiltrating macrophages, CD31+ tumor vessels in a xenograft mouse model of human myxoid liposarcoma (MLS). Trabectedin partial decreases PTX3.

Finally, Trabectedin (Ecteinascidin 743) is a tetrahydroisoquinoline alkaloid with potent antitumor activity.


Takahashi N, et al. Cancer Res. 2002 Dec 1;62(23):6909-15.