Year: 2016
Type: article
Abstract: // Guoping Zhao 1, 6 , Aaron M. Neely 1 , Christian Schwarzer 3 , Huayi Lu 4 , Aaron G. Whitt 1 , Nicole S. Stivers 1 , Joseph A. Burlison 2 , Carl White 5 , Terry E. Machen 3 , Chi Li 1 1 Molecular Targets Program, University of Louisville, Louisville, KY 40202, USA 2 Structural Biology Program, James Graham Brown Cancer Center, Departments of Medicine, Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA 3 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA 4 Second Hospital of Jilin University, Changchun, Jilin Province, P.R. China 130041 5 Department of Physiology and Biophysics, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA 6 Institute of Technical Biology and Agriculture Engineering, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui Province, P.R. China 230031 Correspondence to: Chi Li, e-mail: [email protected] Keywords: homoserine lactone, Bcl-2, Bak, Bax, tumor Received: July 17, 2015 Accepted: December 22, 2015 Published: January 07, 2016 ABSTRACT Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule for bacterial communication. C12 has also been reported to induce apoptosis in various types of tumor cells. However, the detailed molecular mechanism of C12-triggerred tumor cell apoptosis is still unclear. In addition, it is completely unknown whether C12 possesses any potential therapeutic effects in vivo . Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in tumor cells through inducing mitochondrial membrane permeabilization independent of both pro- and anti-apoptotic Bcl-2 proteins. Importantly, C12 inhibits tumor growth in animals regardless of either pro- or anti-apoptotic Bcl-2 proteins. Furthermore, opposite to conventional chemotherapeutics, C12 requires paraoxonase 2 (PON2) to exert its cytotoxicity on tumor cells in vitro and its inhibitory effects on tumor growth in vivo . Overall, our results demonstrate that C12 inhibits tumor growth independent of both pro- and anti-apoptotic Bcl-2 proteins, and through inducing unique apoptotic signaling mediated by PON2 in tumor cells.
Source: Oncotarget
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: Johns Hopkins University, University of Louisville, Cystic Fibrosis Research, National Natural Science Foundation of China, National Institutes of Health, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Center for Research Resources
Awards: G190185007, Molecular Targets Phase III CoBRE, G2841885092, Regulation of apoptosis by Bcl-XL, Bak and Bax, G3337023614, G3655049467, Molecular mechanisms of action of macrolide antibiotics, G4761834745, NDC for the Optical Control of Biological Function, G543988770, Molecular Targets COBRE, G8155442978, G9000142129, G9000186460
OpenAlex ID: W2235965240