Title:Celastrol Inhibits the Proliferation and Induces Apoptosis of Colorectal Cancer Cells
via Downregulating NF-κB/COX-2 Signaling Pathways
Volume: 22
Issue: 10
Author(s): Hua Zhang, Xiaojin Zhao, Fajun Shang, Huan Sun, Xu Zheng and Jiabin Zhu*
Affiliation:
- Department of Neurosurgery, The Affiliated Renhe Hospital, China Three Gorges University, Yichang 443000, China
- Central
Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital,
Yichang 443003, China
Keywords:
Colorectal cancer, celastrol, cell proliferation, apoptosis, nuclear factor-κB, cyclooxygenase-2.
Abstract:
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.
Objective: To reveal the therapeutic effect and underlying mechanisms of celastrol on CRC cells.
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.
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-κB p65 and subsequently leading to cytoplasmic retention of p65 protein, thereby
inhibiting its nuclear translocation and transcription activities.
Conclusion: These findings indicate that celastrol is an effective inhibitor for CRC, regulating the NF-κB/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.
