Anticancer activity of arborinine from Glycosmis parva leaf extract in human cervical cancer cells

Biochem Biophys Res Commun. 2018 Jun 12;500(4):866-872. doi: 10.1016/j.bbrc.2018.04.175. Epub 2018 May 1.

Abstract

Glycosmis parva is a small shrub found in Thailand. Ethyl acetate (EtOAc) extract from its leaves has been shown to exert anticancer effects in vitro; however, the compound responsible for this activity has not been isolated and characterized. In this study, we demonstrate that arborinine, a major acridone alkaloid in the EtOAc fraction, decreased proliferation and was strongly cytotoxic to HeLa cervical cancer cells without significantly affecting normal cells. The compound also inhibited tumor spheroid growth much more potently than chemotherapeutic drugs bleomycin, gemcitabine, and cisplatin. In addition, unlike cisplatin, arborinine activated caspase-dependent apoptosis without inducing DNA damage response. We further show that arborinine strongly suppressed cancer cell migration by downregulating expression of key regulators of epithelial-mesenchymal transition. Taken together, our data provide important insights into the molecular mechanism of arborinine's anticancer activity, supporting its potential use for treating cervical cancer.

Keywords: Arborinine; Cervical cancer; Epithelial-mesenchymal transition; Glycosmis parva.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / isolation & purification
  • Acridines / pharmacology*
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Bleomycin / pharmacology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Line, Transformed
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Dermis / cytology
  • Dermis / drug effects
  • Dermis / metabolism
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gemcitabine
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Plant Extracts / chemistry
  • Plant Leaves / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rutaceae / chemistry*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Spheroids, Cellular / pathology
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Acridines
  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • BCL2 protein, human
  • BCL2L1 protein, human
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Deoxycytidine
  • Bleomycin
  • arborinine
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7
  • Cisplatin
  • Gemcitabine