Inhibition of NF-kappa B augments sensitivity to 5-fluorouracil/folinic acid in colon cancer

The Journal of Surgical Research
Rene VoborilS Mackay

Abstract

5-fluorouracil (5-FU), the most common antimetabolite used for the treatment of colorectal cancer, exerts its cytotoxic effects through the induction of apoptosis. Folinic acid potentiates the effect of 5-FU. Drug activity is currently limited as a result of inducible chemoresistance. Limited research suggests that the transcription factor nuclear factor kappa-B (NF-kappaB), which has antiapoptotic properties, may play a major role in inducible chemoresistance. SW48 colon cancer cells were used for all experiments. Cell growth was determined by cell proliferation assay. Apoptosis was assessed by measuring caspase 3 activity. Activation of NF-kappaB was ascertained by electrophoretic mobility shift assay, luciferase reporter assay, and Western blot analysis. Treatment with 5-FU (0.001-10 mm), not only inhibited growth and induced apoptosis but significantly activated NF-kappaB in SW48 cells. Folinic acid alone (0.01-100 mg/L) did not inhibit growth but improved the cytotoxic effect of 5-FU in a dose-dependent manner. Likewise, folinic acid alone did not activate NF-kappaB or induce apoptosis but enhanced 5-FU-mediated NF-kappaB activation and cell apoptosis. Transfection with adenovirus IkappaBalpha super-repressor strongly inhi...Continue Reading

References

Nov 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·R G MoranC Heidelberger
Apr 1, 1997·Nature Medicine·N Baldini
Sep 17, 1999·The Journal of Biological Chemistry·M Karin
Apr 29, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G J PetersH M Pinedo
Nov 9, 2000·Proceedings of the National Academy of Sciences of the United States of America·D S O'ConnorD C Altieri
Apr 30, 2002·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·N C TebbuttD Kerr
May 11, 2002·Nature Reviews. Cancer·Michael KarinZhi-Wei Li
Jun 27, 2002·Biochimica Et Biophysica Acta·G J PetersH M Pinedo
Feb 14, 2003·International Journal of Cancer. Journal International Du Cancer·Weiguang WangJames Cassidy

❮ Previous
Next ❯

Citations

Mar 31, 2007·Cancer Chemotherapy and Pharmacology·Karen W Barbour, Franklin G Berger
Aug 29, 2009·Molecules and Cells·Young-Sam ImJoong-Kook Choi
Aug 19, 2006·Expert Opinion on Investigational Drugs·Panagiotis A Konstantinopoulos, Athanasios G Papavassiliou
Apr 30, 2014·Journal of Experimental & Clinical Cancer Research : CR·Evandro Luís NieroGláucia Maria Machado-Santelli
Dec 13, 2005·The Journal of Surgical Research·Jing LiSteven N Hochwald
Jun 25, 2010·Nutrition and Cancer·Jens E SlagsvoldSvanhild A Schønberg
Oct 5, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Johanna C BendellDonald A Richards
May 17, 2005·Expert Review of Proteomics·Pier Giorgio RighettiSabina Carla Righetti
Nov 21, 2008·Clinical and Vaccine Immunology : CVI·Xiaoping ChenCharles E McCall
Jul 21, 2020·Journal of Food Biochemistry·Amirhossein DavoodvandiSadegh Jafarnejad
Jun 15, 2018·World Journal of Surgical Oncology·Ashley B WardShailesh Singh
Dec 1, 2019·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Silpa NarayananZhe-Sheng Chen
Apr 21, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jie YingYu Lu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

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.

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