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Curated Journal Articles on Mesothelioma

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma

Oncotarget 2017 February 7 [Epub ahead of print] [Link]

Pellegrini L, Xue J1 Larson D, Pastorino S, Jube S, Forest KH, Saad-Jube ZS, Napolitano A, Pagano I, Negi VS, Bianchi ME, Morris P, Pass HI, Gaudino G, Carbone M, Yang H

Abstract

Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts. Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease

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