New meta-analysis shows no cancer risk with angiotensin-receptor blockers

Mearns, Bryony M.

doi:10.1038/nrcardio.2011.41

Cited by 2 publications

(4 citation statements)

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“…This antiproliferative effect was observed with high doses of AT1 blockers that are not clinically relevant and may have serious side effects, such as hypotension and kidney failure. Recently published meta-analyses had confusing results on the risk of cancer among AT1 blocker-treated patients (Sipahi et al, 2010;Mearns, 2011). Accordingly, we assessed the effect of clinically relevant doses of candesartan on the progression of prostate cancer using a xenograft model in nude mice.…”

Section: Discussionmentioning

confidence: 99%

“…One of the major targets of these analyses was the angiotensin II receptor type 1 blockers (ARBs), which are commonly prescribed for the management of cardiovascular diseases. The results of these analyses were controversial, with some suggesting a causal link between cancer (Sipahi et al, 2010) and ARBs, whereas others dispute such a link (Mearns, 2011). To further complicate the matter, there is a plethora of experimental evidence that suggests a possible beneficial role of ARBs in the management of multiple types of cancer, especially urogenital cancers (Miyajima et al, 2002;Kosaka et al, 2007;Takahashi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, a number of meta-analyses investigating a possible link between cancer incidence and cardiovascular disease drugs have been published (Sipahi et al, 2010;Mearns, 2011). One of the major targets of these analyses was the angiotensin II receptor type 1 blockers (ARBs), which are commonly prescribed for the management of cardiovascular diseases.…”

Section: Introductionmentioning

confidence: 99%

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Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

Alhusban

Al-Azayzih

Goc

et al. 2014

J Pharmacol Exp Ther

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Angiotensin II receptor type 1 blockers (ARBs), widely used antihypertensive drugs, have also been investigated for their anticancer effects. The effect of ARBs on prostate cancer in experimental models compared with meta-analysis data from clinical trials is conflicting. Whereas this discrepancy might be due to the use of supratherapeutic doses of ARBs in cellular and animal models as compared with the clinical doses used in human trials, further investigation of the effects of clinical doses of ARBs on prostate cancer in experimental models is warranted. In the current study, we sought to determine the effects of candesartan on prostate cancer cellular function in vitro and tumor growth in vivo, and characterize the underlying mechanisms. Our analysis indicated that clinically relevant doses of candesartan significantly inhibited growth of PC3 cell tumor xenografts in mice.Interestingly, the same concentrations of candesartan actually promoted prostate cancer cellular function in vitro, through a modest but significant inhibition in apoptosis. Inhibition of tumor growth by candesartan was associated with a decrease in vascular endothelial growth factor (VEGF) expression in tumors and inhibition of tumor angiogenesis, but normalization of tumor vasculature. Although candesartan did not impair PC3 cell viability, it inhibited endothelialbarrier disruption by tumor-derived factors. Furthermore, candesartan significantly inhibited expression of VEGF in PC3 and DU145 cell lines independent of angiotensin II type 2 receptor, but potentially via angiotensin II type 1 receptor inhibition. Our findings clearly demonstrate the therapeutic potential of candesartan for prostate cancer and establish a link between ARBs, VEGF expression, and prostate tumor angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

Alhusban

Al-Azayzih

Goc

et al. 2014

J Pharmacol Exp Ther

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“…Our study further demonstrates that the RAS potentially plays a role in CRC and that the use of well-studied RAS-directed therapies, such as ACEIs, ARBs, and renin inhibitors, may be of benefit for adjunctive treatment of CRC. It is worth mentioning that many trials have been run to determine if RAS blockers can cause cancer and the evidence is overwhelmingly against any relation between RAS blockers and increased risk of cancer in general [103][104][105][106]. ACE gene expression was marginally significantly reduced in the CRC tumor samples, i.e., it was significant on its own, but not with the multiple comparison correction.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer

Mehranfard

Pérez

Rodríguez

et al. 2021

J Renin Angiotensin Aldosterone Syst

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Hypothesis/Introduction. Recent studies suggest involvement of the renin-angiotensin system (RAS) in cancers, including colorectal cancer (CRC). This study focuses on the association of genes encoding 17 proteins related to the RAS within a Japanese male CRC population. Materials and Methods. Quantitative expression of the RNA of these 17 genes in normal and cancerous tissues obtained using chip arrays from the public functional genomics data repository, Gene Expression Omnibus (GEO) application, was compared statistically. Results. Expression of four genes, AGT (angiotensinogen), ENPEP (aminopeptidase A) MME (neprilysin), and PREP (prolyl endopeptidase), was significantly upregulated in CRC specimens. Expression of REN (renin), THOP (thimet oligopeptidase), NLN (neurolysin), PRCP (prolyl carboxypeptidase), ANPEP (aminopeptidase N), and MAS1 (Mas receptor) was downregulated in CRC specimens. Conclusions. Presuming gene expression parallel protein expression, these results suggest that increased production of the angiotensinogen precursor of angiotensin (ANG) peptides, with the reduction of the enzymes that metabolize it to ANG II, can lead to accumulation of angiotensinogen in CRC tissues. Downregulation of THOP, NLN, PRCP, and MAS1 gene expression, whose proteins contribute to the ACE2/ANG 1-7/Mas axis, suggests that reduced activity of this RAS branch could be permissive for oncogenicity. Components of the RAS may be potential therapeutic targets for treatment of CRC.

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New meta-analysis shows no cancer risk with angiotensin-receptor blockers

Cited by 2 publications

References 1 publication

Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

Clinically Relevant Doses of Candesartan Inhibit Growth of Prostate Tumor Xenografts In Vivo through Modulation of Tumor Angiogenesis

Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer

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