Two Active Compounds from Caesalpinia sappan L. in Combination with Cisplatin Synergistically Induce Apoptosis and Cell Cycle Arrest on WiDr Cells

Abstract

Purpose: The aim of this study is to observe the synergistic effect of two active compounds of secang, brazilin and brazilein, combined with cisplatin on WiDr colon cancer cells. Methods: Cytotoxic activities of brazilin (Bi) and brazilein (Be) in single and in combination with cisplatin (Cisp) were examined by MTT assay. Synergistic effect was analyzed by combination index (CI) parameter. Apoptosis and cell cycle profiles were observed by using flow cytometry. Results: The result of MTT assay showed that IC50 value of brazilin and brazilein on WiDr cancer cells were 41 µM and 52 µM respectively. The combination of ½ IC50 of Bi-Cisp reduced cells viability up to 64% and showed synergistic effect with CI value less than 1 (CI = 0.8). The combinations of ½ IC50 of Be-Cisp also reduced cells viability up to 78% and showed synergistic effect (CI=0.65). Combination of Bi-Cisp and Be-Cisp induced apoptosis higher than the single treatments. Further analysis on the cell cycle progression showed that single treatment of ½ IC50 of Be and Bi induced S-phase and G2/M-phase accumulation, while combination of Be-Cisp and Bi-Cisp enhanced S-phase accumulation. Conclusion: Both combination of Bi-Cisp and Be-Cisp showed synergistic effect on WiDr cells through induction of apoptosis and halted the cell cycle progression, thus, WiDr cells growth were significantly reduced.

Keywords: Brazilin, Brazilein, Caesalpinia sappan, L., Cisplatin, Synergistic effect, WiDr cells