Screening of Natural Products for the Development of Anti-cancer Agents in Non-Small Cell Lung Cancer (NSCLC).

Abstract

Non-small cell lung cancer (NSCLC) is one of main causes of human deaths, because current therapeutic approaches have failed to improve survival rates of patient with NSCLC. To develop effective anti-cancer therapeutic strategies, constant efforts have been made. Natural products have served as one of a main sources for discovering novel anticancer drugs. It has been reported that about 60% of approved cancer chemotherapeutic agents were derived from natural products. In this research, we evaluated a number of natural products derived from various medicinal plants for their potential as anticancer chemopreventive and/or therapeutic drugs. The effects of natural products on proliferation, survival and apoptosis were assessed in NSCLC cells, premalignant, and normal human bronchial epithelial (HBE) cell lines. The MTT assay, anchorage-dependent and –independent colony formation assays and fluorescence-activated cell sorting (FACS) assays, and western blot analysis were used to analyze the proteins involved in cell survival and apoptosis. We also confirmed the in vivo inhibitory effects of a couple of natural products on the growh of H1299 NSCLC xenograft tumors established in NOD/SCID mice. The potential mechanisms, mediating the anti-cancer effects of a potent drug were assessed by using the RTK signaling antibody array kit and by using PCR, western blot and luciferase assays. Several natural products exhibited significant inhibitory effects on the proliferation of premalignant HBE and NSCLC cells with minor influence on normal HBE cells at similar concentrations. Among these products, a drug (compound 1) with these capacities effectively inhibited the IGF-IR signaling pathway by suppressing IGF-2 transcription. We also observed that compound 1 suppressed the growth of NSCLCL xenograft tumor in mice. In summary, our data elucidates the potential of compound 1 as an anticancer chemopreventive and/or therapeutic agent against NSCLC.