Plumbagin induces apoptosis in human Osteosarcoma through ROS generation, endoplasmic reticulum stress and mitochondrial apoptosis pathway

Chia Chia Chao, Sheng Mou Hou, Chieh Chen Huang, Chun Han Hou, Po Chun Chen, Ju Fang Liu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Osteosarcoma is the most common primary bone tumor that occurs in children and adolescents. Osteosarcoma has a poor prognosis and is often unresponsive to chemotherapy. Therefore, it remains a challenge to identify a novel strategy to effectively treat osteosarcoma. The present study demonstrated a novel opportunity in osteosarcoma treatment using the natural compound plumbagin. Plumbagin reduced cell viability in osteosarcoma cells but not normal bone cells, as determined by MTT assay and colony formation assay. Plumbagin induced cell apoptosis by mitochondrial dysfunction, which in turn promoted Ca2+ release and endoplasmic reticulum (ER)-stress, as determined by DAPI staining assay, DNA fragmentation assay, flow cytometry and western blotting analysis. In addition, plumbagin improved reactive oxygen species (ROS) generation, as determined by flow cytometry. Finally, these apoptotic cascades activated caspase-3 and caspase-9 to elicit apoptosis response. Our results demonstrated the anticancer effect of plumbagin by inducing cell apoptosis in osteosarcoma cells. In conclusion, plumbagin activated the apoptosis signaling pathway through eliciting ROS, ER stress, mitochondria dysfunction, and finally causing caspase activation. These results indicated that plumbagin may serve as potential antitumor drug by its multifunctional effects in osteosarcoma.

Original languageEnglish
Pages (from-to)5480-5488
Number of pages9
JournalMolecular Medicine Reports
Volume16
Issue number4
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Apoptosis
  • Endoplasmic reticulum stress
  • Osteosarcoma
  • Plumbagin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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