Targeting Mcl-1 Degradation by Bergenin Inhibits Tumorigenesis of Colorectal Cancer Cells.
Yu GanXiaoying LiShuangze HanLi ZhouWei LiPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Myeloid leukemia 1 (Mcl-1) is frequently overexpressed in human malignancies and emerged as a promising drug target. In this study, we verified the inhibitory effect of bergenin on colorectal cancer cells both in vivo and in vitro. In an in vitro setting, bergenin significantly reduced the viability and colony formation and promoted apoptosis of CRC cells dose-dependently. Bergenin decreased the activity of Akt/GSK3β signaling and enhanced the interaction between FBW7 and Mcl-1, which eventually induced Mcl-1 ubiquitination and degradation. Using the HA-Ub K48R mutant, we demonstrated that bergenin promotes Mcl-1 K48-linked polyubiquitination and degradation. In vivo studies showed that bergenin significantly reduced tumor size and weight without toxicity to vital organs in mice. Overall, our results support the role of bergenin in inhibiting CRC cells via inducing Mcl-1 destruction, suggesting that targeting Mcl-1 ubiquitination could be an alternative strategy for antitumor therapy.
Keyphrases
- cell cycle arrest
- induced apoptosis
- signaling pathway
- endoplasmic reticulum stress
- oxidative stress
- cell death
- endothelial cells
- pi k akt
- bone marrow
- metabolic syndrome
- cancer therapy
- high glucose
- dendritic cells
- stem cells
- diabetic rats
- immune response
- skeletal muscle
- pluripotent stem cells
- induced pluripotent stem cells
- replacement therapy