ArticleBMC complementary and alternative medicine2013
Inhibition of Raf-MEK-ERK and hypoxia pathways by Phyllanthus prevents metastasis in human lung (A549) cancer cell line.
Article in BMC complementary and alternative medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Computational and Cytotoxicity Evaluation of Phyllanthus Urinaria-Derived Compounds as Potential Anti-Cervical Cancer Agents via HPV-16 E6 Oncoprotein Inhibition.International journal of molecular sciences · 2026Article
- Integrative transcriptomics and structure-based screening identifiesFrontiers in bioinformatics · 2026Article
- Meniran (RSC advances · 2025Article
- Impacts ofNarra J · 2024Article
- A Review: Mechanism ofEvidence-based complementary and alternative medicine : eCAM · 2021Review
- Isorhamnetin inhibited migration and invasion via suppression of Akt/ERK-mediated epithelial-to-mesenchymal transition (EMT) in A549 human non-small-cell lung cancer cells.Bioscience reports · 2019Article
- FLOT1 promotes tumor development, induces epithelial-mesenchymal transition, and modulates the cell cycle by regulating the Erk/Akt signaling pathway in lung adenocarcinoma.Thoracic cancer · 2019Article
- The synergistic effect of propofol and ulinastatin suppressed the viability of the human lung adenocarcinoma epithelial A549 cell line.Oncology letters · 2018Article
- A Review of the Phytochemistry and Pharmacology ofFrontiers in pharmacology · 2018Article
- Suppression of ERK1/2 and hypoxia pathways by four Phyllanthus species inhibits metastasis of human breast cancer cells.Journal of food and drug analysis · 2016Article
- Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma.Cell death & disease · 2016Article
- Caveolin-1 promotes Ewing sarcoma metastasis regulating MMP-9 expression through MAPK/ERK pathway.Oncotarget · 2016Article
- MiR-451 suppresses cell proliferation and metastasis in A549 lung cancer cells.Molecular biotechnology · 2015Article
- Thymoquinone inhibits proliferation and invasion of human nonsmall-cell lung cancer cells via ERK pathway.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Proteomic identification of novel differentiation plasma protein markers in hypobaric hypoxia-induced rat model.PloS one · 2014Article
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundLung cancer constitutes one of the malignancies with the greatest incidence and mortality rates with 1.6 million new cases and 1.4 million deaths each year. Prognosis remains poor due to deleterious development of multidrug resistance resulting in less than 15% lung cancer patients reaching five years survival. We have previously shown that Phyllanthus induced apoptosis in conjunction with its antimetastastic action. In the current study, we aimed to determine the signaling pathways utilized by Phyllanthus to exert its antimetastatic activities.
methodsCancer 10-pathway reporter array was performed to screen the pathways affected by Phyllanthus in lung carcinoma cell line (A549) to exert its antimetastatic effects. Results from this array were then confirmed with western blotting, cell cycle analysis, zymography technique, and cell based ELISA assay for human total iNOS. Two-dimensional gel electrophoresis was subsequently carried out to study the differential protein expressions in A549 after treatment with Phyllanthus.
resultsPhyllanthus was observed to cause antimetastatic activities by inhibiting ERK1/2 pathway via suppression of Raf protein. Inhibition of this pathway resulted in the suppression of MMP2, MMP7, and MMP9 expression to stop A549 metastasis. Phyllanthus also inhibits hypoxia pathway via inhibition of HIF-1α that led to reduced VEGF and iNOS expressions. Proteomic analysis revealed a number of proteins downregulated by Phyllanthus that were involved in metastatic processes, including invasion and mobility proteins (cytoskeletal proteins), transcriptional proteins (proliferating cell nuclear antigen; zinc finger protein), antiapoptotic protein (Bcl2) and various glycolytic enzymes. Among the four Phyllanthus species tested, P. urinaria showed the greatest antimetastatic activity.
conclusionsPhyllanthus inhibits A549 metastasis by suppressing ERK1/2 and hypoxia pathways that led to suppression of various critical proteins for A549 invasion and migration.
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