Cytotoxicity, Cell Cycle Arrest, and Apoptosis Induction Activity of Ethyl-p-methoxycinnamate in Cholangiocarcinoma Cell.

Phunuch Muhamad,Wanna Chaijaroenkul,Kesara Na-Bangchang,Luxsana Panrit

doi:10.31557/apjcp.2020.21.4.927

Phunuch Muhamad, Wanna Chaijaroenkul + Show 2 more

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https://doi.org/10.31557/apjcp.2020.21.4.927

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Abstract

Objective:To investigate cytotoxic activity of ethyl-p-methoxycinnamate (EPMC) including its effect on p-glycoprotein (multidrug resistance-1: mdr-1 gene) in human cholangiocarcinoma cell. Methods:Cytotoxic activity of EPMC against human cholangiocarcinoma (CL-6), fibroblast (OUMS-36T-1F), and colon cancer (Caco-2) cell lines were assessed using MTT assay. Selectivity index (SI) was determined as the ratio of IC50 (concentration that inhibits cell growth by 50%) of EPMC in OUMS-36T-1F and that in CL-6 cell. Cell cycle arrest and apoptosis in CL-6 cells were investigated by flow cytometry and fluorescent microscopy. Effect of EPMC on mdr-1 gene expression in CL-6 and Caco-2 was determined by real-time PCR. Results:The median (95% CI) IC50 values of EPMC in CL-6, OUMS-36T-1F, and Caco-2 were 245.5 (243.1-266.7), 899.60 (855.8-966.3) and 347.0 (340.3-356.9) µg/ml, respectively. The SI value of the compound for the CL-6 cell was 3.70. EPMC at IC50 inhibited CL-6 cell division and induced apoptosis compared to untreated control. EPMC exposure did not induce mdr-1 gene expression in both CL-6 and Caco-2 cells. Conclusion:The results suggest the potential role of EPMC in cholangiocarcinoma with a low possibility of drug resistance induction.

Highlights

Cholangiocarcinoma is the bile duct malignancy, which the highest incidence has been reported in the population living in the North-Eastern region of Thailand (Kirstein and Vogel, 2016, Xia et al, 2015)
The potential anticancer activity of K. galanga L. crude extract has previously been reported in the CL-6 cell (Amuamuta et al, 2017; Mahavorasirikul et al, 2010)
The potency of activity of EPMC in CL-6 cell varied with concentrations as its IC25, IC50, and IC90 was 172.3, 245.5, and 498.3 μg/ml, respectively (Table 1)

Summary

Introduction

Cholangiocarcinoma is the bile duct malignancy, which the highest incidence has been reported in the population living in the North-Eastern region of Thailand (Kirstein and Vogel, 2016, Xia et al, 2015). (known as Proh-hom in Thai) exhibits several potential medicinal properties such as analgesic (Sulaiman et al, 2008), anti-inflammatory (Sulaiman, et al, 2008), carminative (Preetha et al, 2016) and sedative activities (Huang et al, 2008). Consumption of this plant promotes heat production that enhances recovery of sickness (Nishidono et al, 2017). Potential drug resistance induction by these compounds should be an issue of concern in the development of novel anticancer agents (Huang et al, 2018). The study aimed to investigate cytotoxic activity of EPMC in in various human cell lines and its effect on drug resistance

Materials and Methods

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Discussion