Abstract Title:

Exploiting Honokiol-induced ER stress CHOP activation inhibits the growth and metastasis of melanoma by suppressing the MITF andβ-catenin pathways.

Abstract Source:

Cancer Lett. 2019 Feb 1 ;442:113-125. Epub 2018 Nov 1. PMID: 30391358

Abstract Author(s):

Chien-Shan Chiu, Cheng-Han Tsai, Ming-Shun Hsieh, Shih-Chuan Tsai, Yee-Jee Jan, Wan-Yu Lin, De-Wei Lai, Sheng-Mao Wu, Hsiang-Yuan Hsing, Jack L Arbiser, Meei-Ling Sheu

Article Affiliation:

Chien-Shan Chiu


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 theβ-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.

Study Type : Animal Study, In Vitro Study

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