Alpha-momorcharin (α-MMC) exerts effective anti-human breast tumor activities but has a narrow therapeutic window in vivo

Alpha-momorchatin (alpha-MMC), a ribosome inactivating protein (RIP) extracted from the seeds of Momordica charantia, exerts anti-tumor, antiviral, and anti-fungal activities. However, alpha-MMC has an obvious toxicity that limits its clinical application. We examined the effect of alpha-MMC on the inhibition of human breast cancer and assessed its general toxicity to find the therapeutic window in vivo for its potential clinical use. It was purified using column chromatography, and then injected into the xenograft nude mouse model induced by MDA-MB-231 and MCF-7. The antitumor efficacy was evaluated with T/C%. Next, the alpha-MMC was injected at a series of doses to Balb/C mice to assess its general toxicity. The MIT assay, the apoptosis test, and the cell cycle inhibition of alpha-MMC in human breast cancer cells were performed. In the xenografted tumors induced by MDA-MB-231 and MCF-7, alpha-MMC exerted an obvious inhibition effects on tumor growth at the dosage of 12 mg/kg and 0.8 mg/kg. For in vivo toxicity experiments of alpha-MMC in Balb/C mice, the minimal toxic dose of alpha-MMC was 1.2 mg/kg. Alpha-MMC induced apoptosis by increasing caspase3 activities, and the cell cycle was arrested at the G(0)/G(1) or G(2)/M phases. The measurements of IC50 were 15.07 mu g/mL, 33.66 mu g/mL, 42.94 mu g/mL for MDA-MB-231, MCF-7 and MDA-MB-453 respectively. Alpha-MMC exhibits anti-tumor effects in human breast cancer in vivo and in vitro. It inhibits breast cancer cells through the inhibition of tumor growth and induction of cell apoptosis. However, due to its obvious toxicity, alpha-MMC has a relatively narrow therapeutic window in vivo. (C) 2014 Elsevier B.V. All rights reserved.