Study on anticancer effect of peptide molecule targeting nucleolin

Abstract

Cancer is a disease with a high mortality rate worldwide, and current conventional therapeutic strategies are still ineffective due to low selectivity to cancer cells. Therefore, more efficacious therapeutic methods are needed, such as targeted therapy, which targets specific genes and proteins directly related to cancer growth and survival. One of the promising markers for this targeted strategy, nucleolin (NCL) is highly expressed in cancer cells and its expression is correlated with a worse cancer prognosis. And also, cytoplasm NCL interacts with diverse mRNA and controls their translation due to the structural characteristic of its four RNA-binding domains. Especially, involvement in proliferation and apoptosis translation provides NCL proto-oncogenic and anti-apoptotic properties. Here we designed and synthesized a novel peptide molecule (AGM-330-CPP) that enables intracellular NCL targeting. By connecting an NCL targeting peptide (AGM-330) to the high-efficiency cell-penetrating peptide (CPP) via a bio-conjugation with maleimide, AGM-330-CPP can target intracellular NCL. Experimental data show that AGM-330-CPP significantly inhibited the viability of cancer cells by inducing programmed cell death, apoptosis. These results indicate that AGM-330-CPP could be a novel therapeutic agent for cancer treatment, targeting intracellular NCL.