Celastrol Inhibits the Proliferation and Induces Apoptosis of Colorectal Cancer Cells via Downregulating NF-κB/COX-2 Signaling Pathways

Author(s):

Hua Zhang, Xiaojin Zhao, Fajun Shang, Huan Sun, Xu Zheng and Jiabin Zhu*   Pages 1921 - 1932 ( 12 )

Abstract:

<p>Background: Colorectal cancer (CRC) is the third-ranked malignant tumor in the world that contributes to the death of a major population of the world. Celastrol, a bioactive natural product isolated from the medicinal plant Tripterygium wilfordii Hook F, has been proved to be an effective anti-tumor inhibitor for multiple tumors. <p> Objective: To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells. <p> Methods: CCK-8 and clonogenic assay were used to analyze the cell proliferation in CRC cells. Flow cytometry analysis was conducted to assess the cell cycle and cell apoptosis. Wound-healing and cell invasion assay were used to evaluate the migrating and invasion capability of CRC cells. The potential antitumor mechanism of celastrol was investigated by qPCR, western blot, and confocal immunofluorescence analyses. <p> Results: Celastrol effectively inhibited CRC cell proliferation by activating caspase-dependent cell apoptosis and facilitating G1 cell cycle arrest in a dose-dependent manner, as well as cell migration and invasion by downregulating the MMP2 and MMP9. Mechanistic protein expression revealed that celastrol suppressed the expression of COX-2 by inhibiting the phosphorylation of NF-&#954;B p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby inhibiting its nuclear translocation and transcription activities. <p> Conclusion: These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-&#954;B/COX-2 pathway, leading to the inhibition of cell proliferation characterized by cell cycle arrest and caspase-dependent apoptosis, providing a potential alternative therapeutic agent for CRC patients.</p>

Keywords:

Colorectal cancer, celastrol, cell proliferation, apoptosis, nuclear factor-&#954;B, cyclooxygenase-2.

Affiliation:

Department of anus & intestine surgery, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000, Department of Gastroenterology, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000, Department of Neurosurgery, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000, Department of Neurosurgery, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000, Department of Neurosurgery, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000, Department of Neurosurgery, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000

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