The Effects of Piperlongumine on NF-κB p65 in TNF-α Induced Inflammatory Response in HeLa Cells
Date Issued
2014
Date
2014
Author(s)
Hong, Bo-En
Abstract
Natural compounds are small molecules extracted from organisms. Many natural compounds from herbals have the properties of anti-inflammation and anti-cancer and they may be covalent drugs according to their structures. The natural compound, piperlongumine, is a small molecule from the Piper species plant, Piper longum. Piperlongumine has been shown to kill certain cancer cells but not the normal cells; furthermore, piperlongumine has the activities for anti-platelet. The extracts of Piper longum also have the ability for anti-inflammation, and piperlongumine is a component of the extracts. However, the anti-inflammatory mechanism of piperlongumine is still unknown. NF-κB is a transcription factor that can activate many genes required for the cell proliferation including inducing secretion of interleukins from leukocytes to increase the activities of cell growth. Therefore, NF-κB is a key regulator of the cell proliferation. The NF-κB hyper-activation can lead to chronic inflammation and diseases such as the cancers. We analyzed the structure of piperlongumine and predicted that piperlongumine may be a covalent drug. Piperlongumine can be attacked by the cysteine residues of some proteins through Michael addition to form the covalent bonds. We used a new methodology to generate anti-piperlongumine polyclonal antibody for target identification, and found that the NF-κB can be modified by piperlongumine after piperlongumine treatment in the cells. In the TNF-α (tumor necrosis factor-α) induced NF-κB activation model, we found that the NF-κB translocation from the cytoplasm to the nucleus can be inhibited in cervical cancer cells. Therefore, we predicted that modifications of some cysteine residues on NF-κB can affect the NF-κB translocation and activation.
Subjects
piperlongumine
共價藥物
麥可加成反應
NF-κB
SDGs
Type
thesis
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