Antagonistic Growth Inhibitory Effect of Caged Xanthones with Chemotherapeutic Agents against Human Cholangiocarcinoma KKU-M214 Cell Line

Abstract

Background and Objective : Cholangiocarcinoma (CCA) is a malignant tumor of cholangiocytes, characterized by a poor prognosis and poor response to conventional chemotherapeutic agents.  Our previous studies have demonstrated that isomorellin and isomorellinol inhibited cell growth, induced cell cycle arrest and apoptosis in KKU-100 and KKU-M156 cell lines.  The aim of this study is to examine the growth inhibitory effects of isomorellin, isomorellinol and cisplatin or their combinations on human KKU-M214 cell line.

Methods : KKU-M214 cells were treated with isomorellin, isomorellinol and cisplatin or their combinations and cell viability was determined using sulforhodamine B (SRB) assay.  The interactions between isomorellin or isomorellinol with cisplatin were analyzed by isobologram and combination index (CI) method of Chou-Talalay.

Results :  Concentration of isomorellin, isomorellinol and cisplatin were found to inhibit growth of KKU-M214 cell line in a dose-dependent manner with the IC₅₀ values of 0.61 ± 0.02, 1.12 ± 0.02 and 17.16 ± 0.06 µM, respectively.  The combinations of isomorellin/cisplatin and isomorellinol/cisplatin showed antagonistic effect (CI > 1).

Conclusion: The combination of isomorellin or isomorellinol with cisplatin showed an antagonistic effect on KKU-M214 cells.