Anti-Proliferative Activity of Standardized Methanol Extract of Coscinium fenestratum and Its Major Constituent, Berberine, Against Nasopharyngeal Carcinoma Cells

Maelinda      Daker; Voon      Yee Lin; Gabriel      Akyirem Akowuah; Chiam      Nyet Cheng; Patrick      Nwabueze Okechukwu

Abstract

Nasopharyngeal carcinoma (NPC), prevalent in Southeast Asia and Southern China, is a cancer that develops from the epithelium of the nasopharynx. Current treatments of NPC patients produce undesirable complications. There is growing interest in natural products with anti-proliferative potential to circumvent toxicity associated with synthetic anticancer drugs and radiation. This study evaluated the anti-proliferative activity of standardized methanol extract of Coscinium fenestratum and its major constituent, berberine against two cell lines used as a cell model for NPC. Using HPLC analysis, the content of berberine in the methanol extract of C. fenestratum stem was standardized to be 4.0 % w/w. C. fenestratum standardized methanol extract and berberine inhibited NPC cell proliferation in a concentration- and timedependent manner, determined using the MTS assay. NPC cells were relatively more sensitive than untransformed human skin keratinocyte when treated with both test substances. Cisplatin, a conventional drug, did not show this selectivity, killing the untransformed cells first before the NPC cells. Berberine displayed higher activity, suggesting the possibility that it is the bioactive component. Cell proliferation inhibition was verified by the decrease in Ki67 and PCNA proliferation markers. Growth kinetics was monitored dynamically using an impedance-based system. Flow cytometry analysis revealed that the inhibitory effect of berberine on cell cycle progression was through the arrest of the G1 phase. Morphological changes of NPC cell lines were observed microscopically. The morphological observation and altered growth kinetics were consistent with the cell proliferation and cell cycle progression experiments. This work showed the anti-proliferative properties of berberine, thus its potential use in the formula of natural remedies for the treatment of NPC.

Keywords: Berberine, cell proliferation, cisplatin, Coscinium fenestratum, nasopharyngeal carcinoma