Abstract
Cucurbitacins (Cucs) have been classified as signal transducer and activator of transcription 3 inhibitors. Kinase inhibition has been a validated drug target in multiple types of malignancies. B-RAF mutations are highly expressed in the melanoma. Our hypothesis is the Cucs can be a potential candidate to inhibit the signaling kinase pathway. The research presented is the evaluation of Cucs, as B-RAF and MEK1 kinase inhibitors. Virtual screening methods were employed to identify lead compounds. The hypothesis was tested on mutant B-RAF cell lines, A-375 and Sk-Mel-28 cell lines to determine the activity toward melanoma. A series of natural Cucs show an improved activity toward Sk-Mel-28 and A-375 cell lines. Cucs show potential inhibition for the total and phosphorylated ERK using ELISA kits. Cucs could be potential candidate for inhibiting cell growth.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Cell Line, Tumor
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Cell Survival / drug effects
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Cucurbitacins / chemistry
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Cucurbitacins / pharmacology*
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Cucurbitacins / therapeutic use
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Enzyme-Linked Immunosorbent Assay
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Humans
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MAP Kinase Kinase 1 / antagonists & inhibitors
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MAP Kinase Signaling System / drug effects
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Melanoma / drug therapy*
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Melanoma / enzymology
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Melanoma / pathology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Molecular Docking Simulation
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Molecular Structure
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein Kinase Inhibitors / therapeutic use
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Proto-Oncogene Proteins B-raf / antagonists & inhibitors
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Cucurbitacins
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BRAF protein, human
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Proto-Oncogene Proteins B-raf
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Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 1
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MAP2K1 protein, human