Deciphering the Mechanism of Action Involved in Enhanced Suicide Gene Colon Cancer Cell Killer Effect Mediated by Gef and Apoptin

Cancers
Blanca CáceresHouria Boulaiz

Abstract

Despite the great advances in cancer treatment, colorectal cancer has emerged as the second highest cause of death from cancer worldwide. For this type of tumor, the use of suicide gene therapy could represent a novel therapy. We recently demonstrated that co-expression of gef and apoptin dramatically inhibits proliferation of the DLD-1 colon cell line. In the present manuscript, we try to establish the mechanism underlying the enhanced induction of apoptosis by triggering both gef and apoptin expression in colon tumor cells. Scanning microscopy reveals that simultaneous expression of gef and apoptin induces the apparition of many "pores" in the cytoplasmic membrane not detected in control cell lines. The formation of pores induced by the gef gene and accentuated by apoptin results in cell death by necrosis. Moreover, we observed the presence of apoptotic cells. Performing protein expression analysis using western blot, we revealed an activation of mitochondrial apoptosis (increased expression of Pp53, cytochrome c, Bax, and caspase 9) and also the involvement of the extrinsic pathway through caspase 8activation. In conclusion, in this manuscript we demonstrate for the first time that the extrinsic pathway of apoptosis and pore...Continue Reading

References

Apr 14, 1999·Cell Death and Differentiation·A G Porter, R U Jänicke
Jun 1, 2002·Science·Harald Wajant
Feb 5, 2003·Experimental Cell Research·Sergey Ya ProskuryakovVladimir L Gabai
Jan 28, 2004·Cell·Nika N Danial, Stanley J Korsmeyer
Oct 4, 2005·The Journal of Clinical Investigation·Inna N LavrikPeter H Krammer
Jun 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Xuebin ZhangLee A Bulla
Jul 5, 2006·Molecular Cancer Therapeutics·Wan Seok YangChul-Woo Kim
Dec 5, 2006·Trends in Biochemical Sciences·Pierre Golstein, Guido Kroemer
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Oct 11, 2008·Cell Death and Differentiation·G KroemerUNKNOWN Nomenclature Committee on Cell Death 2009
Dec 1, 2009·Fish & Shellfish Immunology·Po-Chun ChenJiann-Ruey Hong
Mar 23, 2010·Lancet·David CunninghamNaureen Starling
Nov 10, 2011·Toxins·Assaf Shapira, Itai Benhar
Nov 23, 2011·Medical Oncology·Suna ZhouJiansheng Wang
Mar 17, 2012·Cell Death and Differentiation·G WickmanM F Olson
Jul 10, 2012·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Raúl OrtizAntonia Aranega
Sep 18, 2012·Cell Host & Microbe·Mirko BischofbergerF Gisou van der Goot
Nov 23, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaoping YangThomas W Flaig
Jun 5, 2013·Methods in Molecular Biology·S Burattini, E Falcieri
Jul 13, 2013·Cell Death & Disease·K BolandJ H M Prehn
Aug 8, 2013·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Houria BoulaizPrados Jose
Apr 4, 2015·Cold Spring Harbor Perspectives in Biology·David R McIlwainTak W Mak
Oct 22, 2015·Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre·Maitham A Khajah, Yunus A Luqmani
Jan 26, 2016·PloS One·Soshi SeikeMasahiro Nagahama
Jul 19, 2016·Expert Opinion on Therapeutic Patents·Saúl Abenhamar NavarroHouria Boulaiz
Aug 30, 2016·World Journal of Gastroenterology : WJG·Tao HuChi Hin Cho
Aug 31, 2016·World Journal of Gastrointestinal Oncology·Aman M Abraha, Ezra B Ketema
Jan 20, 2017·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Jessica Pahle, Wolfgang Walther
May 17, 2017·Oncoimmunology·Gautier StollGuido Kroemer
Jul 19, 2017·Trends in Cancer·Lorenzo Galluzzi, Guido Kroemer
Sep 2, 2017·Apoptosis : an International Journal on Programmed Cell Death·Monika SachetRudolf Oehler

❮ Previous
Next ❯

Citations

Jul 17, 2020·Frontiers in Cell and Developmental Biology·Waseem Akram MallaAshok Kumar Tiwari
Jan 22, 2021·Life Sciences·Esam Bashir Yahya, Amaal Mohammed Alqadhi
Jul 13, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Olga Cruz-LópezAna Conejo-García

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
optical microscopy
transfection
confocal microscopy
electrophoresis

Software Mentioned

ImageJ
Quantity One

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

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.

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.