Lycorine inhibits melanoma cell migration and metastasis mainly through reducing intracellular levels of β‐catenin and matrix metallopeptidase 9

Metastatic melanoma accounts for 60% of death for skin cancer. Although great efforts have been made to treat the disease in recent decades, effective drugs against metastatic melanoma are lack. We found that lycorine significantly suppressed melanoma cell migration and invasion in vitro, and decreased the metastasis of melanoma cells to lung tissues in mice by reducing intracellular levels of β‐catenin protein through degradation of the protein via the ubiquitin–proteasome pathway. Our findings support the notion that targeting the oncogenic β‐catenin signaling by lycorine is a new option to inhibit melanoma cell metastasis. AbstractMetastatic melanoma accounts for 60% of death for skin cancer. Although great efforts have been made to treat the disease, effective drugs against metastatic melanoma still lack at the clinical setting. In the current study, we found that lycorine, a small molecule of isoquinoline alkaloid, significantly suppressed melanoma cell migration and invasion in vitro, and decreased the metastasis of melanoma cells to lung tissues in tumor ‐bearing mice, resulting in significant prolongation of the survival of the mice without obvious toxicity. Molecular mechanistic studies revealed that lycorine significantly reduced intracellular levels of β‐catenin protein through degradation of the protein via the ubiquitin–proteasome pathw ay, and decreased the expression of β‐catenin downstream prometastatic matrix metallopeptidase 9 and Axin2 gen...

Source: Journal of Cellular Physiology - November 22, 2018 Category: Cytology Authors: Pan Zhang, Mengli Zhang, Di Yu, Wenming Liu, Lin Hu, Bin Zhang, Quansheng Zhou, Zhifei Cao Tags: ORIGINAL RESEARCH ARTICLE Source Type: research