Shikonin inhibits invasiveness of osteosarcoma through MMP13 suppression

Tumour Biol. 2015 Dec;36(12):9311-7. doi: 10.1007/s13277-015-3662-1. Epub 2015 Jun 24.

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumor, notorious for its metastasis. We have recently shown that shikonin, an effective constituent extracted from Chinese medicinal herb, induces necroptosis in OS cells. Nevertheless, the effects of low-dose shikonin on the invasiveness of OS cells are unknown. Here, we showed that shikonin dose-dependently decreased OS cell invasiveness in both scratch wound healing assay and transwell cell migration assay. Moreover, the direct target of shikonin on cell invasiveness was found to be matrix metalloproteinase (MMP)-13. Further, the inhibitory effects of shikonin on cell invasiveness were completely abolished in MMP13-overexpressing OS cells. Together, these data suggest that shikonin may suppress OS invasiveness through MMP13 suppression. Thus, our data highlight a previous unappreciated role for shikonin in suppressing OS cell metastasis.

Keywords: Matrix metalloproteinase (MMP)-13; Osteosarcoma (OS); Shikonin.

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Matrix Metalloproteinase 13 / biosynthesis*
  • Matrix Metalloproteinase 13 / genetics
  • Naphthoquinones / administration & dosage*
  • Neoplasm Invasiveness / genetics
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology

Substances

  • Naphthoquinones
  • shikonin
  • Matrix Metalloproteinase 13