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

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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-1effects on apoptosis and metastasis signaling pathways were studied using Western blotting and gene expression. CHM-1 induced G2/M arrest and apoptosis at an IC50 (3 μM) 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 ΔΨm 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 mM). CHM-1 inhibited the cell metastasis through the inhibition of MMP-2,-7, and -9.CHM-1also 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.

Original languageEnglish (US)
Pages (from-to)1637-1644
Number of pages8
JournalJournal of Orthopaedic Research
Volume27
Issue number12
DOIs
StatePublished - Dec 2009

Keywords

  • Antimetastasis
  • Apoptosis
  • CHM-1
  • Caspase cascade
  • Human osterogenic sarcoma U-2 OS cells

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