The Effect of Statins in Colorectal Cancer Is Mediated Through the Bone Morphogenetic Protein Pathway

Kodach, Liudmila L.; Bleuming, Sylvia A.; Peppelenbosch, Maikel P.; Hommes, Daniël W.; Brink, Gijs R. van den; Hardwick, James C.H.

doi:10.1053/j.gastro.2007.08.021

Cited by 69 publications

(66 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A screen of 30 000 compounds for their ability to enhance BMP2 expression for eventual use to enhance bone formation identified two statins as the two most active compounds 25. We have subsequently shown that the actions of statins in CRC depend on their ability to upregulate BMP2 expression and activate the BMP pathway 24. Interestingly, the BMP2 gene is silenced by promoter hypermethylation in a large proportion of gastric cancers,26 but whether this also occurs in CRCs is unknown.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

Kodach

Jacobs

Voorneveld

et al. 2011

Gut

123

119

View full text Add to dashboard Cite

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway Kodach, L.; Jacobs, R.J.; Voorneveld, P.W.; Wildenberg, M.E.; Verspaget, H.W.; van Wezel, T.; Morreau, H.; Hommes, D.W.; Peppelenbosch, M.P.; van den Brink, G.R.; Hardwick, J.C.H. Published in: Gut DOI:10. 1136/gut.2011.237495 Link to publication Citation for published version (APA):Kodach, L. L., Jacobs, R. J., Voorneveld, P. W., Wildenberg, M. E., Verspaget, H. W., van Wezel, T., ... Hardwick, J. C. H. (2011). Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway. Gut, 60(11), 1544-1553. DOI: 10.1136/gut.2011 General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.

show abstract

Section: Introductionmentioning

confidence: 97%

“…In vitro studies show that statins inhibit cellular proliferation and induce apoptosis in CRC cells and in animal models 23 24. A screen of 30 000 compounds for their ability to enhance BMP2 expression for eventual use to enhance bone formation identified two statins as the two most active compounds 25.…”

Section: Introductionmentioning

confidence: 99%

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

Kodach

Jacobs

Voorneveld

et al. 2011

Gut

123

119

View full text Add to dashboard Cite

show abstract

“…Lastly, patients on chronic therapy with entirely distinct drug classes, e.g. selective serotonin reuptake inhibitors (SSRIs) or simvastatin-type cholesterol-lowering pharmaceuticals, are likewise at significantly lower risk of developing colorectal cancer (Kodach et al, 2007;Xu et al, 2006).…”

Section: Potential Relevance To Red/processed Meat Consumptionmentioning

confidence: 99%

Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association

Hammerling

Laurila

Grafström

et al. 2015

Critical Reviews in Food Science and Nutrition

View full text Add to dashboard Cite

Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

show abstract

“…CRC cell lines were analyzed for their content in the bone morphogenetic factor 2 (BMP2), in relation to their sensitivity to statins. It was found that cells expressing high levels of the protein in response to statins (SAOS2, HCT116, DLD1) were much more sensitive to apoptosis induction than cells (HT--29, SW480) in which the BMP pathway was not activated by statins [86].…”

Section: 24--colon Cancermentioning

confidence: 99%

Statins: Perspectives in cancer therapeutics

Corcos

Jossic-Corcos

2013

Digestive and Liver Disease

View full text Add to dashboard Cite

Virtually any cell type in a mammalian organism uses Acetyl CoA to yield mevalonate, through the activity of the 3--hydroxy--3--methyl--glutaryl--CoA (HMG--CoA) reductase enzyme and, ultimately, cholesterol. Statins have long and quite successfully been used as cholesterol lowering drugs. They reversibly inhibit the HMG--CoA reductase activity, which is rate limiting in the early steps of the cholesterol synthesis pathway. In addition to these effects, it has also been amply shown that statins may efficiently trigger cancer cell apoptosis, making them a plausible therapeutic option for the treatment of cancer. Whether statins may prevent from cancer occurrence is a matter of debate and an unanswered question, but no doubt experimental models have clearly demonstrated the potential of statins as direct cytotoxic agents, which can reduce tumor development or metastasis spreading, even more so when combined to cytotoxic drugs. Until now, however, only few data in humans support the idea that statins could rightfully enter the contingent of anticancer drugs. Nevertheless, at times where cancer cells metabolism is getting very much revisited, the mevalonate pathway has recently been reported as truly oncogenic, bringing upfront the attractive possibility to see mevalonate pathway blunting agents, such as statins, join the wealth of anticancer drugs.

show abstract

The Effect of Statins in Colorectal Cancer Is Mediated Through the Bone Morphogenetic Protein Pathway

Cited by 69 publications

References 34 publications

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

Statins augment the chemosensitivity of colorectal cancer cells inducing epigenetic reprogramming and reducing colorectal cancer cell 'stemness' via the bone morphogenetic protein pathway

Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association

Statins: Perspectives in cancer therapeutics

Contact Info

Product

Resources

About