Abstract

Alpha-momorcharin (α-MMC) is a ribosome-inactivating protein (RIP) with antitumor and antiviral activities. α-MMC has a tumoricidal effect on choriocarcinoma, which is a malignant trophoblast-derived tumor that can arise during any type of gestation. To develop the therapeutic potential of α-MMC, we performed surface site-specific modification by covalent attachment of a 20 kDa amino derivative poly(ethylene glycol), which is (mPEG)2-Lys-NHS. We evaluated the potency of α-MMC and the PEGylated α-MMC as potential anti-metastatic drugs to combat this disease. We conducted a quantitative 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide  (MTT) test, adhesion assay, wound healing assay, matrigel invasion assay and gelatin zymography to test the cell viability and proliferation, cell adhesion, migration and invasiveness, and the activities of matrix metalloproteinases (MMPs) on JAR cells after protease treatment. We found that native and PEGylated α-MMC significantly inhibited the growth of choriocarcinoma JAR cells in a dose- and time- dependent manner. Zymography showed that they both potently attenuated the activity of matrix-metalloproteinase-2 (MMP-2), which is associated with decreased cell movement potential. The in vitro migration and invasion assays confirmed these results. The inhibitory effect of α-MMC and its PEGylated conjugates on the metastatic stage of human choriocarcinoma JAR cells suggests a possible novel role for RIPs such as α-MMC in tumor progression.

Key words: Alpha-momorcharin (α-MMC), choriocarcinoma, migration and invasion, matrix-metalloproteinase-2 (MMP-2), Alpha-momorcharin PEGylated anti-tumor activity (PEG-α-MMC).