NSAID inhibition of GI cancer growth: clinical implications and molecular mechanisms of action

The American Journal of Gastroenterology
Syeda S HusainAndrzej S Tamawski

Abstract

Epidemiological studies suggest that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of and mortality from colorectal, gastric, and esophageal cancers. The precise mechanisms by which NSAIDs exert their chemopreventive effects are not fully explained, but likely involve inhibition of cyclo-oxygenase, the enzyme that converts arachidonic acid to prostaglandins. Two isoforms of this enzyme, cyclo-oxygenase 1 (COX-1) and COX-2, have been identified. COX-2 is absent in normal mucosa but is overexpressed in colonic, gastric, and esophageal cancers, as well as their precursor lesions. The inhibition of COX-2 through either pharmacological agents or gene deletion results in suppression of colonic polyp formation. NSAIDs reduce colonic, gastric, and esophageal cancer cell growth, in part, by inducing apoptosis. However, the antineoplastic effects of NSAIDs may be partly independent of their ability to inhibit COX-2. The mechanisms involved in the antineoplastic actions of NSAIDs include inhibition of angiogenesis (essential for delivery of oxygen and nutrients to a growing tumor), induction of apoptosis (which is usually reduced in cancer cells) by stimulation of proapoptotic genes, and direct inhi...Continue Reading

References

Jan 1, 1978·Journal of Chronic Diseases·H A IsomäkiU Joutsenlahti
May 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·O J PlesciaK Grinwich
Apr 1, 1992·Carcinogenesis·P A Craven, F R DeRubertis
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·T Hla, K Neilson
Aug 9, 1991·Science·K W KinzlerD McKechnie
Nov 1, 1991·The Journal of Pediatrics·F M GiardielloS R Hamilton
Dec 15, 1991·Annals of Internal Medicine·J RigauJ M Bordas
Dec 15, 1991·The New England Journal of Medicine·M J ThunC W Heath
Mar 6, 1991·Journal of the National Cancer Institute·L RosenbergS Shapiro
Dec 15, 1989·Biochemical and Biophysical Research Communications·C Yokoyama, T Tanabe
Nov 18, 1989·BMJ : British Medical Journal·A Paganini-HillB E Henderson
Dec 1, 1986·The American Journal of Surgical Pathology·R C Haggitt, B J Reid
Jan 1, 1986·Epidemiologic Reviews·C P HowsonE L Wynder
Feb 1, 1983·Proceedings of the Society for Experimental Biology and Medicine·D M Form, R Auerbach
Sep 1, 1983·Diseases of the Colon and Rectum·J S ThompsonP E Hodgson
Sep 1, 1983·Journal of Surgical Oncology·W R Waddell, R W Loughry
Oct 1, 1995·Gastroenterology·T LiuP R Holt
Sep 7, 1995·The New England Journal of Medicine·E GiovannucciF E Speizer
Apr 1, 1995·Gastroenterology·J LadenheimM B Omary
Nov 1, 1994·Digestive Diseases and Sciences·A D MüllerI H Wasserman
Aug 15, 1994·Annals of Internal Medicine·E GiovannucciW C Willett
Jan 20, 1994·Nature·J Vane
Mar 1, 1994·Epidemiology·D M Schreinemachers, R B Everson
Aug 15, 1993·Cancer·O SuhN J Petrelli
May 6, 1993·The New England Journal of Medicine·F M GiardielloG J Offerhaus
Feb 17, 1993·Journal of the National Cancer Institute·G GridleyJ F Fraumeni
Jun 2, 1993·Journal of the National Cancer Institute·E R GreenbergR Haile
Jun 2, 1993·Journal of the National Cancer Institute·J E Muscat, E L Wynder
Jun 19, 1993·International Journal of Cancer. Journal International Du Cancer·D M ParkinJ Ferlay
Apr 1, 1996·Gastroenterology·R N DuBoisA J Entingh
Oct 1, 1995·Cancer·E M Funkhouser, G B Sharp
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·W KutcheraS M Prescott

❮ Previous
Next ❯

Citations

Jun 13, 2003·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·A C DrakeM G Dunlop
Aug 17, 2006·Journal of Gastroenterology and Hepatology·Haim ShirinEmilia M Sordillo
Sep 21, 2002·BMJ : British Medical Journal·Roger Jones
Feb 10, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Anna E PrizmentKristin E Anderson
Jan 30, 2016·Inorganic Chemistry·Emilia PăunescuPaul J Dyson
Sep 6, 2003·ANZ Journal of Surgery·Giuseppe GarceaDavid P Berry
Apr 20, 2007·Chemical Biology & Drug Design·Marko MarjanovićMarijeta Kralj
Jun 28, 2016·Digestive Diseases and Sciences·Elena PiazueloAngel Lanas
May 6, 2014·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Natalia KhalafHashem B El-Serag
Mar 12, 2009·Veterinary Pathology·S J BaekA M Legendre
Nov 7, 2017·Medicinal Chemistry Research : an International Journal for Rapid Communications on Design and Mechanisms of Action of Biologically Active Agents·Bini MathewRobert C Reynolds
Jan 6, 2005·World Journal of Gastroenterology : WJG·Dong-Sheng HuangHai-Yang Xie
Jan 11, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Balamurugan Kuppusamy, Howard A Young
Aug 13, 2009·Digestive Diseases and Sciences·Ping YangXiao-Ting Wu
Jul 14, 2010·Journal of Gastroenterology and Hepatology·Takashi KawaiAkira Yamashina
Mar 2, 2018·The Open Medicinal Chemistry Journal·Bini MathewRobert C Reynolds
May 5, 2011·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·Lei Sun, Shiying Yu
Dec 24, 2002·The Journal of Pharmacy and Pharmacology·Tat Khuen Lee, Ieva Stupans
Oct 5, 2011·Alimentary Pharmacology & Therapeutics·A P ThriftD C Whiteman
Mar 3, 2009·Annals of the New York Academy of Sciences·Antonella CusimanoMelchiorre Cervello
Oct 9, 2004·International Journal of Cancer. Journal International Du Cancer·Susanne Dihlmann, Magnus von Knebel Doeberitz
May 24, 2006·World Journal of Gastroenterology : WJG·Yun Dai, Wei-Hong Wang
Apr 20, 2018·Future Medicinal Chemistry·Bini MathewRobert C Reynolds
May 29, 2018·Journal of Enzyme Inhibition and Medicinal Chemistry·Adel S El-AzabMagda A-A El-Sayed
Sep 25, 2017·Bioorganic & Medicinal Chemistry Letters·Bini MathewRobert C Reynolds

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adenomatous Polyposis Coli

Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.

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

Angiogenesis Inhibitors to Treat Cancer

Cancer treatments including angiogenesis inhibitors prevent tumor cells from receiving nutrients and oxygen. Here is the latest research on angiogenesis inhibitors for the treatment of cancer.

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.

Atrophic Gastritis

Atrophic Gastritis is a process where gastric glandular cells are lost and replaced with firbous tissues, as a result of chronic inflammation. Learn more about Atrophic Gastritis here.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.