Back to Search
Start Over
Exploiting Honokiol-induced ER stress CHOP activation inhibits the growth and metastasis of melanoma by suppressing the MITF and β-catenin pathways
- Source :
- Cancer letters. 442
- Publication Year :
- 2018
-
Abstract
- There is increasing global incidence of highly metastatic melanoma and therapeutic strategies like those focusing on the downstream beta-catenin/MITF axis of invading melanoma cells are urgently needed. Targeting endoplasmic reticulum (ER) stress can promote cancer cell death and inhibit epithelial mesenchymal transition (EMT) in metastatic tumors. This study aimed to determine if Honokiol could promote ER stress-dependent apoptosis and regulate metastatic melanoma. The therapeutic efficacy of Honokiol was assessed using the highly metastatic melanoma xenograft mouse model for peritoneal metastasis and evaluated by computed tomography imaging. The ER stress marker, Calpain-10, delineated a novel proteolytic cleavage enzyme, while CHOP/GADD153-regulated apoptosis was used for gene silencing to determine the role of the β-catenin/MITF axis in melanoma cells. The results showed that Honokiol effectively decreased peritoneal dissemination and organ metastasis via ER stress activation and EMT marker inhibition. Knockdown Calpain-10 or CHOP/GADD153 blocked all of the biological effects in Honokiol-induced β-catenin/MITF cleavage, ERSE or TCF/LEF luciferase activity, and β-catenin kinase activity. These findings suggest that Honokiol can significantly thwart the progression of highly metastatic melanoma using the β-catenin/MITF axis via prompt Calpain-10 and CHOP/GADD153 regulated cascades.
- Subjects :
- 0301 basic medicine
Honokiol
Male
Cancer Research
Skin Neoplasms
Mice, Nude
CHOP
Lignans
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Movement
Cell Line, Tumor
medicine
Animals
Humans
Epithelial–mesenchymal transition
Kinase activity
Melanoma
Wnt Signaling Pathway
Peritoneal Neoplasms
beta Catenin
Cell Proliferation
Mice, Inbred BALB C
Microphthalmia-Associated Transcription Factor
Calpain
Biphenyl Compounds
Cyclin-Dependent Kinase 2
Microphthalmia-associated transcription factor
medicine.disease
Endoplasmic Reticulum Stress
Antineoplastic Agents, Phytogenic
Xenograft Model Antitumor Assays
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Unfolded protein response
Transcription Factor CHOP
Subjects
Details
- ISSN :
- 18727980
- Volume :
- 442
- Database :
- OpenAIRE
- Journal :
- Cancer letters
- Accession number :
- edsair.doi.dedup.....b112cfd0c7a911e36bed6fb6d12847f4