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

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.

SUBMITTER: Tan BL

PROVIDER: S-EPMC6241369 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Tan Bee Ling BL Norhaizan Mohd Esa ME Chan Lee Chin LC

Evidence-based complementary and alternative medicine : eCAM 20181105

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 ...[more]

PMID: 30519270

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Project description:The plant Manilkara zapota belongs to the family Sapotaceae and is commonly known as Chiku in Pakistan. Traditionally, M. zapota is used in pulmonary diseases, diarrhea, rheumatism, hemorrhage, and ulcers. There is no study available on the in vivo antiarthritic activity of M. zapota and its gold nanoparticles (AuNPs). The aim of this study is to evaluate the in vivo acute and sub-acute antiarthritic activity of aqueous extract of M. zapota and its biosynthesized gold nanoparticles (AuNPs). Plant-induced reduction method was used for the synthesis of AuNPs. The synthesized AuNPs were characterized via UV, FTIR, SEM, and zeta potential measurements and were optimized by screening various parameters including time, temperature, pH, and salt concentration. Arthritis in rats was induced by Freund's Complete Adjuvant (FCA) injection in hind paw. The antiarthritic effect was evaluated by the determination of paw volume, joint diameter, latency time, hematological, biochemical parameters, antioxidant biomarkers, TNF-α level, and radiological evaluation. The aqueous extract and nanoparticles significantly decreased the paw volume, joint diameter, and significantly increased latency time as compared to the FCA-induced arthritic group. They significantly normalized the hematological, biochemical parameters, and oxidative stress biomarkers in comparison to the arthritic group. They also significantly decreased the TNF-α level when assessed against the arthritic group. Radiological evaluation confirmed the antiarthritic effect of the aqueous extract and nanoparticles of M. zapota leaf extract. It is concluded that the aqueous extract and nanoparticles of M. zapota possess significant analgesic, antiarthritic, and anti-inflammatory activity. However, nanoparticles possess more pronounced antiarthritic activity as compared to the aqueous extract. Moreover, free radical scavenging action and TNF-α reduction showed a prominent role in their antiarthritic activity. Further, investigation is underway to identify the active phytochemical constituent responsible for the antiarthritic activity.

Dataset Information

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

Publications

<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.

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