N-(3-oxo-acyl) homoserine lactone induced germ cell apoptosis and suppressed the over-activated RAS/MAPK tumorigenesis via mitochondrial-dependent ROS in C. elegans

Apoptosis : an International Journal on Programmed Cell Death
Bin ChenGuoping Zhao

Abstract

As a quorum-sensing molecule for bacteria-bacteria communication, N-(3-oxododecanoyl)-homoserine lactone (C12) has been found to possess pro-apoptotic activities in various cell culture models. However, the detailed mechanism of how this important signaling molecule function in the cells of live animals still remains largely unclear. In this study, we systematically investigated the mechanism for C12-mediated apoptosis and studied its anti-tumor effect in Caenorhabditis elegans (C. elegans). Our data demonstrated that C12 increased C. elegans germ cell apoptosis, by triggering mitochondrial outer membrane permeabilization (MOMP) and elevating the reactive oxygen species (ROS) level. Importantly, C12-induced ROS increased the expression of genes critical for DNA damage response (hus-1, clk-2 and cep-1) and genes involved in p38 and JNK/MAPK signaling pathway (nsy-1, sek-1, pmk-1, mkk-4 and jnk-1). Furthermore, C12 failed to induce germ cell apoptosis in animals lacking the expression of each of those genes. Finally, in a C. elegans tumor-like symptom model, C12 significantly suppressed tumor growth through inhibiting the expression of RAS/MAPK pathway genes (let-23/EGFR, let-60/RAS, lin-45/RAF, mek-2/MEK and mpk-1/MAPK). Overall...Continue Reading

References

Apr 11, 1995·Proceedings of the National Academy of Sciences of the United States of America·M Hara, M Han
Jan 4, 1994·Proceedings of the National Academy of Sciences of the United States of America·J P PearsonE P Greenberg
Aug 2, 2000·Proceedings of the National Academy of Sciences of the United States of America·M R Parsek, E P Greenberg
Jan 4, 2001·Microbes and Infection·K P RumbaughA N Hamood
Feb 28, 2001·Proceedings of the National Academy of Sciences of the United States of America·A Aballay, F M Ausubel
Dec 19, 2001·Current Biology : CB·S AhmedA Gartner
Feb 23, 2002·Trends in Genetics : TIG·Nicholas JozaJosef M Penninger
Apr 4, 2003·The Journal of Biological Chemistry·Nanami Senoo-MatsudaNaoaki Ishii
Dec 20, 2003·Cell Death and Differentiation·L Stergiou, M O Hengartner
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Guillaume Lettre, Michael O Hengartner
May 27, 2006·Cell Death and Differentiation·L S SalinasR E Navarro
Aug 17, 2006·Genes & Development·Ekaterini A KritikouMichael O Hengartner
Aug 31, 2007·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shunchang WangLijun Wu
Jun 21, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Maxwell C K LeungJoel N Meyer
Dec 9, 2008·The Biochemical Journal·Michael P Murphy
Mar 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Swathi ArurTim Schedl
Jan 5, 2010·Free Radical Biology & Medicine·Magdalena L Circu, Tak Yee Aw
May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Alice T ShawTyler Jacks
Jan 10, 2012·Methods in Cell Biology·Ashley L CraigAnton Gartner
Jul 4, 2012·Journal of Biosciences·N R Jena
Sep 25, 2012·Nature Reviews. Cancer·Douglas C Wallace
Feb 26, 2013·Journal of the National Cancer Institute·Jean-Pierre GilletMichael M Gottesman
Apr 12, 2013·Oxidative Medicine and Cellular Longevity·Zhang YiranLiu Zongping
May 3, 2016·Saudi Pharmaceutical Journal : SPJ : the Official Publication of the Saudi Pharmaceutical Society·Abdelaziz Ghanemi
Apr 1, 2015·Molecular & Cellular Oncology·Emmanouil KyriakakisNektarios Tavernarakis

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
confocal microscopy
fluorescence microscopy

Software Mentioned

Pro Plus
Image

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

Cancer Metabolism

In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.