Manilkara zapota (L.) P. Royen Leaf Water Extract Induces Apoptosis in Human Hepatocellular Carcinoma (HepG2) Cells via ERK1/2/Akt1/JNK1 Signaling Pathways. (5th November 2018)

• Record Type: Journal Article
• Authors: Tan, Bee Ling; Norhaizan, Mohd Esa; Chan, Lee Chin
• Other Names: Kucuk Omer Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2018(2018)
• Publication Date: 2018-11-05
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2018/7826576
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : 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.