Inhibition of NF-kappaB sensitizes human pancreatic carcinoma cells to apoptosis induced by etoposide (VP16) or doxorubicin

Oncogene
A ArltH Schäfer

Abstract

The transcription factor NF-kappaB has anti-apoptotic properties and may confer chemoresistance to cancer cells. Here, we describe human pancreatic carcinoma cell lines that differ in the responsiveness to the topoisomerase-2 inhibitors VP16 (20 microM) and doxorubicin (0.3 microM): Highly sensitive T3M4 [corrected] and PT45-P1 cells, and Capan-1 and A818-4 cells that were almost resistant to both anti cancer drugs. VP16, but not doxorubicin, transiently induced NF-kappaB activity in all cell lines, whereas basal NF-kappaB binding was nearly undetectable in T3M4 [corrected] and PT45-P1 cells, but rather high in Capan-1 and A818-4 cells, as demonstrated by gel-shift and luciferase assays. Treatment with various NF-kappaB inhibitors (Gliotoxin, MG132 and Sulfasalazine), or transfection with the IkappaBalpha super-repressor, strongly enhanced the apoptotic effects of VP16 or doxorubicin on resistant Capan-1 and 818-4 cells. Our results indicate that under certain conditions the resistance of pancreatic carcinoma cells to chemotherapy is due to their constitutive NF-kappaB activity rather than the transient induction of NF-kappaB by some anti-cancer drugs. Blockade of basal NF-kappaB activity by well established drugs efficiently r...Continue Reading

References

Apr 1, 1996·The Journal of Experimental Medicine·H L PahlP A Baeuerle
Nov 14, 1997·Proceedings of the National Academy of Sciences of the United States of America·W SchmiegelE V Jensen
Apr 16, 1998·The Journal of Clinical Investigation·C WahlR M Schmid
May 15, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·C HellerbrandD A Brenner
Sep 28, 1998·Biochimica Et Biophysica Acta·P S Kingma, N Osheroff
Oct 24, 1998·The Journal of Biological Chemistry·G Kothny-WilkesT Schwarz
Oct 31, 1998·Brain Research. Molecular Brain Research·A SalminenT Suuronen
Aug 24, 1999·Molecular and Cellular Biology·K A SheppardT Collins
Dec 22, 1999·Oncogene·M Barkett, T D Gilmore
Jan 8, 2000·Acta Psychiatrica Scandinavica·C Y LiuH C Liu

❮ Previous
Next ❯

Citations

May 29, 2010·Amino Acids·Thiruvengadam Arumugam, Craig D Logsdon
Dec 1, 2007·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·Bryan HolcombC Max Schmidt
Mar 12, 2004·Cancer Letters·Florian R Greten, Michael Karin
Apr 23, 2003·Archives of Biochemistry and Biophysics·Maud AndriolloPascale Guiraud
Jun 5, 2003·Journal of Pediatric Surgery·Jeffrey S UppermanHenri R Ford
Aug 29, 2003·The Journal of Surgical Research·Bridget N FahyRichard J Bold
Jul 12, 2002·Drug Discovery Today·Burkhard Haefner
Nov 17, 2001·Current Opinion in Pharmacology·J Robert
Apr 2, 2005·Nature Reviews. Cancer·Chikashi Nakanishi, Masakazu Toi
Jan 18, 2006·Cell Death and Differentiation·S Janssens, J Tschopp
Dec 21, 2006·Journal of the National Cancer Institute·Thiruvengadam ArumugamCraig D Logsdon
Oct 9, 2012·Cancer Research·Ratika SrivastavaEduardo Davila
Jun 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thiruvengadam ArumugamCraig D Logsdon
Apr 1, 2009·Future Medicinal Chemistry·P Veeraraghavan RamachandranC Max Schmidt
Mar 14, 2014·Pancreas·Tomoya ShamotoHiromitsu Takeyama
Apr 29, 2009·Digestive Diseases and Sciences·Yoichi MatsuoSushovan Guha
Sep 17, 2015·International Journal of Cancer. Journal International Du Cancer·Yiwen BuDeliang Cao
May 1, 2007·Expert Opinion on Therapeutic Targets·Jen Jen Yeh, Channing J Der

❮ Previous
Next ❯

Related Concepts

Related Feeds

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