Antrodin C Isolated from Antrodia Cinnamomea Induced Apoptosis through ROS/AKT/ERK/P38 Signaling Pathway and Epigenetic Histone Acetylation of TNFα in Colorectal Cancer Cells.
Yung-Yu HsiehKo-Chao LeeKung-Chuan ChengKam-Fai LeeYa-Ling YangHsin-Tung ChuTing-Wei LinChin-Chu ChenMeng-Chiao HsiehCheng-Yi HuangHsing-Chun KuoChih-Chuan TengPublished in: Antioxidants (Basel, Switzerland) (2023)
Treatment with antrodin C triggered the activation of extrinsic apoptosis pathways (TNFα, Bax, caspase-3, and -9), and also suppressed the expression of anti-apoptotic molecules Bcl-2 in HCT-116 cells in a time-dependent manner. Antrodin C also decreased cell proliferation and growth through the inactivation of cyclin D1/cyclin for the arrest of the cell cycle at the G1 phase. The activation of the ROS/AKT/ERK/P38 pathways was involved in antrodin-C-induced transcriptional activation, which implicates the role of the histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFα promoters. Immunohistochemical analyses revealed that antrodin C treatment significantly induced TNFα levels, whereas it decreased the levels of PCNA, cyclin D1, cyclin E, and MMP-9 in an in vivo xenograft mouse model. Thus, antrodin C induces cell apoptosis via the activation of the ROS/AKT/ERK/P38 signaling modules, indicating a new mechanism for antrodin C to treat CRC in vitro and in vivo.
Keyphrases
- cell cycle
- induced apoptosis
- signaling pathway
- cell proliferation
- cell cycle arrest
- pi k akt
- cell death
- endoplasmic reticulum stress
- rheumatoid arthritis
- oxidative stress
- epithelial mesenchymal transition
- dna methylation
- dna damage
- diabetic rats
- high glucose
- mouse model
- gene expression
- transcription factor
- reactive oxygen species
- endothelial cells