Potent USP10/13 antagonist spautin-1 suppresses melanoma growth via ROS-mediated DNA damage and exhibits synergy with cisplatin.

Journal of Cellular and Molecular Medicine
Jia GuoHong Liu

Abstract

Malignant melanoma is one of the most invasive tumours. However, effective therapeutic strategies are limited, and overall survival rates remain low. By utilizing transcriptomic profiling, tissue array and molecular biology, we revealed that two key ubiquitin-specific proteases (USPs), ubiquitin-specific peptidase10 (USP10) and ubiquitin-specific peptidase10 (USP13), were significantly elevated in melanoma at the mRNA and protein levels. Spautin-1 has been reported as a USP10 and USP13 antagonist, and we demonstrated that spautin-1 has potent anti-tumour effects as reflected by MTS and the colony formation assays in various melanoma cell lines without cytotoxic effects in HaCaT and JB6 cell lines. Mechanistically, we identified apoptosis and ROS-mediated DNA damage as critical mechanisms underlying the spautin-1-mediated anti-tumour effect by utilizing transcriptomics, qRT-PCR validation, flow cytometry, Western blotting and immunofluorescence staining. Importantly, by screening spautin-1 with targeted or chemotherapeutic drugs, we showed that spautin-1 exhibited synergy with cisplatin in the treatment of melanoma. Pre-clinically, we demonstrated that spautin-1 significantly attenuated tumour growth in a cell line-derived xenog...Continue Reading

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Oct 24, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yiran Han, C Chris Yun
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Jun 4, 2021·Cancer Management and Research·Baoxue DuanXiaoyu Yang

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Methods Mentioned

BETA
ubiquitination
Assay
transfection
electrophoresis
fluorescence microscopy
xenograft
xenografts
flow cytometry

Software Mentioned

FlowJo10
Calcusyn
FlowJo
ModFit
GraphPad Prism
QuantStudio3 Real Time PCR System

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis