Novel quinolone CHM-1 induces apoptosis and inhibits metastasis in a human osterogenic sarcoma cell line

✍ Scribed by Shu-Chun Hsu; Jai-Sing Yang; Chao-Lin Kuo; Chyi Lo; Jing-Pin Lin; Te-Chun Hsia; Jen-Jyh Lin; Kuang-Chi Lai; Hsiu-Maan Kuo; Li-Jiau Huang; Sheng-Chu Kuo; W. Gibson Wood; Jing-Gung Chung

• Publisher: Elsevier Science
• Year: 2009
• Tongue: English
• Weight: 495 KB
• Volume: 27
• Category: Article
• ISSN: 0736-0266
• DOI: 10.1002/jor.20937

✦ Synopsis

Abstract

Novel 2‐phenyl‐4‐quinolone compounds have potent cytotoxic effects on different human cancer cell lines. In this study, we examined anticancer activity and mechanisms of 20‐fluoro‐6,7‐methylenedioxy‐2‐phenyl‐4‐quinolone (CHM‐1) in human osterogenic sarcoma U‐2 OS cells. CHM‐1‐induced apoptosis was determined by flow cytometric analysis, DAPI staining, Comet assay, and caspase inhibitors. CHM‐1‐inhibited cell migration and invasion was assessed by a wound healing assay, gelatin zymography, and a Transwell assay. The mechanisms of CHM‐1 effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM‐1 induced G2/M arrest and apoptosis at an IC~50~ (3 µ__M__) in U‐2 OS cells and caspase‐3, ‐8, and ‐9 were activated. Caspase inhibitors increased cell viability after exposure to CHM‐1. CHM‐1‐induced apoptosis was associated with enhanced ROS generation, DNA damage, decreased ΔΨ~m~ levels, and promotion of mitochondrial cytochrome c release. CHM‐1 stimulated mRNA expression of caspase‐3, ‐8, and ‐9, AIF, and Endo G. In addition, CHM‐1 inhibited cell metastasis at a low concentration (<3 µ__M__). CHM‐1 inhibited the cell metastasis through the inhibition of MMP‐2, ‐7, and ‐9. CHM‐1 also decreased the levels of MAPK signaling pathways before leading to the inhibition of MMPs. In summary, CHM‐1 is a potent inducer of apoptosis, which plays a role in the anticancer activity of CHM‐1. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1637–1644, 2009