Phyllanthus urinaria 's Inhibition of Human Osteosarcoma Xenografts Growth in Mice is Associated with Modulation of Mitochondrial Fission/Fusion Machinery

Sheng Teng Huang*, Chao Chun Huang, Jer Ming Sheen, Tsu Kung Lin, Pei Lin Liao, Wen Liang Huang, Pei Wen Wang, Chia Wei Liou, Jiin Haur Chuang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

14 Scopus citations

Abstract

Osteosarcoma is an aggressive bone cancer arising from primitive transformed cells of mesenchymal origin to form malignant osteoid. Phyllanthus urinaria (P. urinaria) is a widely used folk medicine in cancer treatment, however the mechanism of P. urinaria inhibited human osteosarcoma is unclear. The present study was aimed at investigating the antitumoral effects of an aqueous P. urinaria on human osteosarcoma in vivo and the related underlying mechanisms, mainly focusing on mitochondrial dynamic dysfunction. Our results showed that oral administration of P. urinaria to mice led to significant inhibition of tumor development without substantial changes to body weight or major organs. Histological examinations with H&E, Giemsa, and Masson trichrome stains confirmed inhibition of tumor growth by the P. urinaria treatment. Immunohistochemical staining of proliferation markers antigen KI-67 (Ki67) and proliferating cell nuclear antigen (PCNA), as well as a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated a decrease of tumor proliferation and an increase of apoptosis, which was associated with the modulation of B-cell lymphoma 2 (Bcl-2) family activating the caspase cascade in the P. urinaria-treated mice. The neovascularization marker cluster of differentiation 31 (CD31) was inhibited in P. urinaria-treated xenografts, implicating the potential anti-angiogenic effect of P. urinaria. P. urinaria treatment resulted in a significant decrease in the mitochondrial fusion proteins, including mitofusin 1/2 (Mfn1/2) and optic atrophy type 1 (Opa1), as well as an increase in the fission protein dynamin-related protein 1 (Drp1). The results of this study suggest mitochondrial dysfunction is associated with dynamic change that is involved in the apoptosis and anti-angiogenesis elicited by P. urinaria.

Original languageEnglish
Pages (from-to)1507-1523
Number of pages17
JournalAmerican Journal of Chinese Medicine
Volume44
Issue number7
DOIs
StatePublished - 01 10 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 World Scientific Publishing Company.

Keywords

  • Angiogenesis
  • Apoptosis
  • Mitochondrial Dynamics
  • Phyllanthus urinaria

Fingerprint

Dive into the research topics of 'Phyllanthus urinaria 's Inhibition of Human Osteosarcoma Xenografts Growth in Mice is Associated with Modulation of Mitochondrial Fission/Fusion Machinery'. Together they form a unique fingerprint.

Cite this