ACT001 inhibits pituitary tumor growth by inducing autophagic cell death via MEK4/MAPK pathway
Lin Cai1, Ze-Rui Wu1, Lei Cao2
1Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Abstract:
ACT001, derived from traditional herbal medicine, is a novel compound with effective anticancer activity in clinical trials. However, little is known regarding its role in pituitary adenomas. Here, we demonstrated that ACT001 suppressed cell proliferation and induced cell death of pituitary tumor cells in vitro and in vivo. ACT001 was also effective in suppressing the growth of different subtypes of human pituitary adenomas. The cytotoxic mechanism ACT001 employed was mainly related to autophagic cell death (ACD), indicated by autophagosome formation and LC3-II accumulation. In addition, ACT001-mediated inhibitory effect decreased when either ATG7 was downregulated or cells were cotreated with autophagy inhibitor 3-methyladenine (3-MA). RNA-seq analysis showed that mitogen-activated protein kinase (MAPK) pathway was a putative target of ACT001. Specifically, ACT001 treatment promoted the phosphorylation of JNK and P38 by binding to mitogen-activated protein kinase kinase 4 (MEK4). Our study indicated that ACT001-induced ACD of pituitary tumor cells via activating JNK and P38 phosphorylation by binding with MEK4, and it might be a novel and effective anticancer drug for pituitary adenomas.
Insights
ACT001, a novel herbal compound, effectively inhibits pituitary tumor growth by inducing autophagic cell death (ACD). It targets the MAPK pathway, offering a potential new treatment for pituitary adenomas.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Pituitary adenomas are common tumors with limited treatment options.
- The therapeutic potential of ACT001, a novel herbal compound, in pituitary adenomas is largely unexplored.
Purpose of the Study:
- To investigate the efficacy and mechanism of ACT001 against pituitary adenomas.
- To explore ACT001's role in cell proliferation, cell death, and specific signaling pathways.
Main Methods:
- In vitro and in vivo studies using pituitary tumor cells.
- Assessment of cell proliferation, cell death, and autophagosome formation.
- RNA sequencing (RNA-seq) to identify molecular targets.
- Western blotting to analyze protein phosphorylation.
Main Results:
- ACT001 suppressed pituitary tumor cell proliferation and induced cell death in vitro and in vivo.
- ACT001 triggered autophagic cell death (ACD), evidenced by autophagosome formation and LC3-II accumulation.
- ACT001 activated the JNK and P38 pathways by binding to MEK4, suggesting MAPK pathway involvement.
Conclusions:
- ACT001 demonstrates significant anticancer activity against pituitary adenomas.
- The compound induces ACD in pituitary tumor cells via MEK4-mediated JNK and P38 phosphorylation.
- ACT001 represents a promising novel therapeutic agent for pituitary adenomas.
More Related Videos
09:51Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
Published on: June 30, 2023
07:15Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:31The Intrinsic Apoptotic Pathway
02:34Inhibition of Cdk Activity
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:23Abnormal Proliferation