Combination Therapy of Eurycomanone and Doxorubicin As Anticancer on T47D and MCF-7 Cell Lines

Abstract

Hanifah Yusuf, Denny Satria, Suryawati Suryawati, Marhami Fahriani

Doxorubicin (DOXO) is an anticancer that is often used clinically which induces cardiotoxicity in the patient. Therefore, finding a new compound that acts as co-chemotherapy is a current challenge. Eurycomanone (EURY) isolated from Eurycoma longifolia Jack have been shown to have anticancer activity in several studies. This study aimed to observe the effect of EURY, DOXO, and its combination on the cell cycle of T47D and MCF-7 breast cancer cell lines. Anticancer activities of EURY and DOXO were examined by MTT colorimetry assay. The effect of combination was analyzed by the Combination Index (CI) method using Compusyn software. The apoptotic activity was analyzed using flow cytometry. To determine CI, a fixed concentration ratio between EURY and DOXO was used from the IC50 value at concentrations (1/2; 1/4; 1/8; 1/16 of IC50). We found that EURY had IC50 values at 0.377μg/mL on T47D and 4.7μg/mL on MCF-7 cells, while DOXO had IC50 values 1.845μg/mL on T47D and 5.074μg/mL on MCF-7cells. The optimal combination of EURY and DOXO on T47D was at 1/16 IC50 EURY – 1/6 IC50 DOXO with CI of 0.3442, whereas on MCF-7 was at 1/16 IC50 of EURY – ½ IC50 DOXO with CI 0.0221. Apoptosis was significantly higher in MCF-7 cells treated with EURY alone than DOXO alone with p<0.001. On T47D cells, DOXO alone resulted in more cell death than EURY alone, although not statistically significant. Cell death was higher in both cancer lines when EURY and DOXO were combined compared to DOXO alone with p<0.05 in both comparisons.