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

Kitiya Piboonprai; Phattharachanok Khumkhrong; Mattaka Khongkow; Teerapong Yata; Nijsiri Ruangrungsi; Chaisak Chansriniyom; Tawin Iempridee

doi:10.1016/j.bbrc.2018.04.175

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.

Authors

Kitiya Piboonprai¹, Phattharachanok Khumkhrong¹, Mattaka Khongkow¹, Teerapong Yata¹, Nijsiri Ruangrungsi², Chaisak Chansriniyom³, Tawin Iempridee⁴

Affiliations

¹ National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand.
² Department of Pharmacognosy, Faculty of Pharmacy, Rangsit University, Pathum Thani, Thailand.
³ Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
⁴ National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani, Thailand. Electronic address: [email protected].

PMID: 29705700
DOI: 10.1016/j.bbrc.2018.04.175

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