2-Deoxyglucose induces cell cycle arrest and apoptosisin colorectal cancer cells independent of its glycolysis inhibition

Nutrition and Cancer
Pratik MuleyHemachand Tummala

Abstract

2-Deoxyglucose (2DG) is an anticancer drug with excellent safety profile. Because of its higher dose requirements, its potential is yet to translate into a monotherapy. However, recently, 2DG has been tested as an adjunct in established chemotherapeutic regimens. 2DG enhanced the potency of several chemotherapeutic agents but not all. The rationale selection of known chemotherapeutic agents to use with 2DG is hampered because of the lack of complete understanding of mechanism behind 2DG anticancer effects. Although, 2DG is a well-known glycolytic inhibitor, which inhibits the key glycolytic enzyme hexokinase, its anticancer effects cannot be fully explained by this simplistic mechanism alone. In this article, we have shown for the first time that 2DG induced a transient expression of p21 and a continuous expression of p53 in colorectal cancer cells (SW620). The treatment also caused cell cycle arrest at G0/G1 phase and induced apoptosis through the mitochondrial pathway. The effects of 2DG on p21 and p53 protein levels were totally independent of its inhibitory effect on either hexokinase or ATP levels. Results from this study provides key insights into novel molecular mechanisms of 2DG and directs rational selection of other a...Continue Reading

References

Oct 31, 2000·International Journal of Cancer. Journal International Du Cancer·I NaruseM Mori
Mar 6, 2002·The Journal of Biological Chemistry·Zhiyong HanJames H Wyche
Apr 5, 2003·Cancer Cell·Osamu Tetsu, Frank McCormick
Jun 20, 2003·Cell Proliferation·Katrien VermeulenZwi N Berneman
Jun 15, 2007·Toxicologic Pathology·Susan Elmore
Jul 14, 2007·Antioxidants & Redox Signaling·Metin KurtogluTheodore J Lampidis
Nov 14, 2008·Proceedings of the National Academy of Sciences of the United States of America·Markus RalserHans Lehrach
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Apr 23, 2009·Molecular Oncology·Linda Strandberg IhrlundMaria C Shoshan
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Mar 5, 2011·The Journal of Biological Chemistry·Takeharu SakamotoMotoharu Seiki
Aug 16, 2011·Clinical & Experimental Metastasis·Joseph L SottnikDouglas H Thamm
Mar 21, 2012·Cancer Research·Gang ChengBalaraman Kalyanaraman
Oct 16, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Venkata Reddy Bandugula, Rajendra Prasad N
Nov 17, 2012·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Madita ReutterCarsten Gründker
Nov 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marie BénéteauJean-Ehrland Ricci
Apr 10, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·M J Duffy

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence activated cell sorter

Software Mentioned

CellFIT
SigmaPlot®
ImageJ

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.