Duku (Lansium domesticum) Leaves Extract Induces Cell Cycle Arrest and Apoptosis of HepG2 Cells via PI3K/Akt Pathways

Liver cancer is a type of malignant cancer that causes many deaths in the world. Efforts to find natural ingredients that can be used to treat liver cancer are very important. This study investigated the anticancer activity of ethanol extract of Duku (Lansium domesticum) leaves (LDE) through the cytotoxic activity, cell cycle inhibition mechanism and apoptosis influence through the PI3K/Akt pathways. Secondary metabolites of LDE were determined by common qualitative method. Cell cycle arrest was carried out by flow cytometer at inhibitory concentration 50 (IC50), while the apoptosis test was obtained using double staining method. The IC50 value was used to identifying the expression of PI3K/Akt genes. The analyzed results were proven LDE can induce HepG2 cell death which IC50 value of 19.93 ± 0.93 μg/mL (ethanol extract), 267.06 ± 3.24 μg/mL (ethyl acetate extract), and 216.47 ± 2.87 μg/mL (n-hexane extract). Cell cycle arrest activity in HepG2 cells which IC50 value of ethanol extract of LDE occurs in S phase. Observation of apoptosis occurrence was obtained getting apoptosis in cell line.  PI3K/Akt genes expression of ethanol extract of LDE was obtained using RT-PCR method. The bands density of PI3K/Akt at IC50 value treatment of 0.55 ± 0.02; 0.25 ± 0.01. The LDE was determined to contain secondary metabolites which can inhibit the growth of HepG2 cells through PI3K/Akt pathways. 
HIGHLIGHTS 
 
The ethanolic extract of Lansium domesticum leaves have the best cytotoxic activity against HepG2 cells line compared to ethyl acetate extract and n-hexane extract 
The ethanolic extract of Lansium domesticum leaves have anticancer activity against HepG2 cells line through cell cycle arrest and apoptosis induce 
The ethanolic extract of Lansium domesticum leaves can inhibit the expressions of PI3K/Akt/mTOR genes using RT-PCR 
 
GRAPHICAL ABSTRACT