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Manilkara zapota  (L.) P. Royen, called sapodilla, or locally known as  ciku , belongs to the family  Sapotaceae . We found that  Manilkara zapota  leaf water extract has cytotoxic effect against human hepatocellular carcinoma (HepG2) cell line in our earlier study. Therefore, this study aimed to explore the anticancer properties of  Manilkara zapota  leaf water extract in HepG2 cells. We also aimed to unravel yet undiscovered mechanisms and identified several expressed genes whose functions in cytotoxicity activity of  Manilkara zapota  leaf water extract in HepG2 cells have not been well-studied. The apoptosis and intracellular reactive oxygen species (ROS) activities were analyzed using Annexin V-propidium iodide staining and dichlorodihydrofluorescein diacetate, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were assessed using Enzyme-Linked Immunosorbent Assay. The associated molecular pathways were evaluated by quantitative real-time PCR. Overall analyses revealed that  Manilkara zapota  leaf water extract can increase percentage of early apoptotic cells, induce the formation of ROS, upregulate c-Jun N-terminal kinase 1 ( JNK1 ) and inducible nitric oxide synthase ( iNOS ), and reduce  Akt1  and vascular endothelial growth factor A ( VEGFA ) transcriptional activities. Our data suggest that  Manilkara zapota  leaf water extract can suppress the growth of HepG2 cells via modulation of  ERK1/2 / Akt1 / JNK1  transcriptional expression.

evidence-based complementary and alternative medicine

<i>Manilkara zapota</i> (L.) P. Royen Leaf Water Extract Induces Apoptosis in Human Hepatocellular Carcinoma (HepG2) Cells via ERK1/2/Akt1/JNK1 Signaling Pathways

Manilkara zapota (L.) P. Royen Leaf Water Extract Induces Apoptosis in Human Hepatocellular Carcinoma (HepG2) Cells via ERK1/2/Akt1/JNK1 Signaling Pathways