Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice

Araújo, Wedson F.; Naves, Marcelo Andery; Ravanini, Juliana Naves; Schor, Nestor; Teixeira, Vicente P.C.

doi:10.1016/j.urolonc.2014.11.022

Cited by 32 publications

(39 citation statements)

References 44 publications

(45 reference statements)

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“…Furthermore, experimental studies have implicated a potential role of the renin‐angiotensin‐aldosterone system (which regulates BP) in the biological processes of cellular proliferation, inflammation, angiogenesis and tissue remodeling . Studies in mice have also provided preliminary evidence that blockade of the angiotensin II type 1 receptor attenuates the growth and metastatic potential of RCC …”

Section: Introductionmentioning

confidence: 99%

“…20 Studies in mice have also provided preliminary evidence that blockade of the angiotensin II type 1 receptor attenuates the growth and metastatic potential of RCC. 21 In the context of the above considerations, the aim of our study was to further explore the association between hypertension and cancer. We examined whether measured SBP and DBP were associated with the risk of incident cancer at all anatomical sites in the large and well-established European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, after taking into account obesity, smoking and other lifestyle and dietary factors (for both men and women) and indicators of sexual maturation and reproductive life (for women), which could be potential confounders or shared risk factors for cancer and hypertension.…”

Section: Introductionmentioning

confidence: 99%

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Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Christakoudi

Κακούρου

Markozannes

et al. 2019

Intl Journal of Cancer

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Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC‐participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow‐up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08–1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14–1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07–1.26) (SBP), HR = 1.31 (1.13–1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04–1.12) (SBP), HR = 1.09 (1.01–1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82–1.00) and lymphomas: HR = 0.97 (0.93–1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Christakoudi

Κακούρου

Markozannes

et al. 2019

Intl Journal of Cancer

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“…proved that candesartan dramatically decreased metastatic lung tumors by inhibiting tumor angiogenesis . Similarly, a recent report showed that RAS blockade decreased tumor proliferation and the metastatic potential of RCC in a murine metastatic model . Although RAS inhibitors, such as candesartan and the other ARB except telmisartan, showed no induction of cell cytotoxicity and apoptosis, only telmisartan showed cytotoxicity in urogenital cancer in vitro , as telmisartan has not only AT1R blockade, but also peroxisome proliferator‐activated receptor γ activation …”

Section: Ras In Urological Diseases (Table )mentioning

confidence: 91%

“…19 Similarly, a recent report showed that RAS blockade decreased tumor proliferation and the metastatic potential of RCC in a murine metastatic model. 94 Although RAS inhibitors, such as candesartan and the other ARB except telmisartan, showed no induction of cell cytotoxicity and apoptosis, only telmisartan showed cytotoxicity in urogenital cancer in vitro, as telmisartan has not only AT1R blockade, but also peroxisome proliferatoractivated receptor c activation. 95 Tatokoro et al carried out a phase II trial of combination treatment consisting of interferon-a, cimetidine, cyclooxygenase-2 inhibitor and RAS drugs in 51 patients with advanced RCC.…”

Section: Rccmentioning

confidence: 98%

Renin–angiotensin system blockade: Its contribution and controversy

et al. 2015

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Angiotensin II is a key biological peptide in the renin-angiotensin system that regulates blood pressure and renal hemodynamics, and extensive experimental studies have shown that angiotensin II promotes diverse fibrotic changes and induces neovascularization in several inflammatory diseases. It is known that angiotensin II can be controlled using renin-angiotensin system blockade when angiotensin II is the main factor inducing a particular disease, and renin-angiotensin system blockade has assumed a central role in the treatment of inflammatory nephritis, cardiovascular disorders and retinopathy. In contrast, renin-angiotensin system blockade was found to have not only these effects but also other functions, such as inhibition of cancer growth, angiogenesis and metastasis. Numerous studies have sought to elucidate the mechanisms and support these antitumor effects. However, a recent meta-analysis showed that renin-angiotensin system blockade use might in fact increase the incidence of cancer, so renin-angiotensin system blockade use has become somewhat controversial. Although the renin-angiotensin system has most certainly made great contributions to experimental models and clinical practice, some issues still need to be resolved. The present review discusses the contribution and controversy surrounding the renin-angiotensin system up to the present time.

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“…Renal cell carcinoma (RCC) represents the most common form of kidney cancer and its incidence has been increasing (Ho et al, 2013;Wang et al, 2013;Araújo et al, 2015). Additionally, kidney cancer is highly refractory to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Chronic Oxidative Stress Increases Resistance to Doxorubicin-Induced Cytotoxicity in Renal Carcinoma Cells Potentially Through Epigenetic Mechanism

2015

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Renal cell carcinoma is the most common form of kidney cancer and is highly resistant to chemotherapy. Although the role of oxidative stress in kidney cancer is known, the chemotherapeutic response of cancer cells adapted to chronic oxidative stress is not clear. Hence, the effect of oxidative stress on sensitivity to doxorubicin-induced cytotoxicity was evaluated using an in vitro model of human kidney cancer cells adapted to chronic oxidative stress. Results of MTT-and anchorage-independent growth assays and cell cycle analysis revealed significant decrease in sensitivity to doxorubicin in Caki-1 cells adapted to oxidative stress. Changes in the expression of genes involved in drug transport, cell survival, and DNA repair-dependent apoptosis further confirmed increased resistance to doxorubicin-induced cytotoxicity in these cells. Decreased expression of mismatch repair (MMR) gene MSH2 in cells exposed to oxidative stress suggests that loss of MMR-dependent apoptosis could be a potential mechanism for increased resistance to doxorubicin-induced cytotoxicity. Additionally, downregulation of HDAC1, an increase in the level of histone H3 acetylation, and hypermethylation of MSH2 promoter were also observed in Caki-1 cells adapted to chronic oxidative stress. DNA-demethylating agent 5-Aza-2dC significantly restored the expression of MSH2 and doxorubicin-induced cytotoxicity in Caki-1 cells adapted to chronic oxidative stress, suggesting the role of DNA hypermethylation in inactivation of MSH2 expression and consequently MMRdependent apoptosis in these cells. In summary, this study for the first time provides direct evidence for the role of oxidative stress in chemotherapeutic resistance in renal carcinoma cells potentially through epigenetic mechanism.

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Renin-angiotensin system (RAS) blockade attenuates growth and metastatic potential of renal cell carcinoma in mice

Cited by 32 publications

References 44 publications

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition

Renin–angiotensin system blockade: Its contribution and controversy

Chronic Oxidative Stress Increases Resistance to Doxorubicin-Induced Cytotoxicity in Renal Carcinoma Cells Potentially Through Epigenetic Mechanism

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