Renin angiotensin system deregulation as renal cancer risk factor (Review)

Sobczuk, Paweł; Szczylik, Cezary; Porta, Camillo; Czarnecka, Anna M.

doi:10.3892/ol.2017.6826

Cited by 44 publications

(73 citation statements)

References 77 publications

(112 reference statements)

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“…The prior published data have demonstrated an association between Ang II and cancer development (22,23). Penafuerte et al (24) revealed that Ang II is a major upstream regulator of cancer cachexia.…”

Section: Discussionmentioning

confidence: 99%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

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Abstract. Expression of angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is closely associated with the occurrence and development of cancer. Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the AT2R, to mediate a series of biological effects. Telmisartan, a specific AT1R blocker, has been reported to have potential as an anticancer drug for treating renal cancer. In the present study, whether telmisartan had an effect on non-small cell lung cancer (NSCLC) cell proliferation and migration was investigated. The Cell Counting kit-8 assay revealed that telmisartan significantly inhibited the growth of the NSCLC A549 cell line in a time-and dose-dependent manner. In a transwell assay, telmisartan significantly inhibited cellular invasion and migration. Furthermore, it was determined that the expression of the anti-apoptotic protein B-cell lymphoma was decreased, and that of the pro-apoptotic proteins caspase-3 and Bcl-associated X increased in the A549 cells treated with telmisartan. Additionally, levels of phosphorylated RAC serine/threonine-protein kinase (p-AKT), p-mechanistic target of rapamycin, p70-S6 kinase and cyclin D1 was decreased in the telmisartan-treated group. Therefore, the current study reveals that telmisartan-induced NSCLC apoptosis may be regulated via the phosphoinositide 3-kinase/AKT signaling pathway, which indicates that it may be a potential novel drug for clinical NSCLC treatment. IntroductionLung cancer, the most common type of cancer, has the highest morbidity rate among all types of malignancies worldwide (1,2), accounting for 30% of all incidences of cancer-associated mortality (3). In clinical practice, the two major types of lung cancer are small cell lung cancer (SCLC) and non-SCLC (NSCLC) (4), of which NSCLC accounts for ~80% of all lung cancer cases (5). Current therapies for NSCLC include chemotherapy, radiotherapy, targeted therapy and surgery, which are used alone or in combination (6). Despite the use of these therapies, the overall 5-year survival rate of NSCLC remains low, at 15% (7). Owing to the development of drug resistance and the severe side effects experienced by patients, effective and safe novel agents are required for the treatment of NSCLC (1).Angiotensin II (Ang II), a key biological peptide in the renin-angiotensin system, is a vasoconstrictor that controls cardiovascular function and renal homeostasis (8). Ang II receptor blockers (ARBs) are extensively used as anti-hypertensive drugs (9). Studies have reported that angiogenesis is essential for tumor progression and metastasis (10,11). Furthermore, studies have demonstrated that ARBs have the potential possibility to restrain the growth of several types of cancer cells (12,13). Ang II binds two receptor subtypes, the Ang II type 1 receptor (AT1R) and the Ang II type 2 receptor (AT2R), to mediate a series of biological effects (14). AT1R mediates the main functions of Ang II, including tumor growth and angiogenesis (15). Treatment with telmisartan, a spe...

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Section: Discussionmentioning

confidence: 99%

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Zhang

Wang

2018

Oncol Lett

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“…Taken together, this area has not been extensively studied and requires further investigation. Others have investigated whether blocking the RAS can either change the incidence of tumours or positively affect tumour treatment 79,80 . Given the large number of different tumours and tumour treatments, this is still an evolving area of investigation.…”

Section: Ace In the Immune Systemmentioning

confidence: 99%

Angiotensin-converting enzyme in innate and adaptive immunity

et al. 2018

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Angiotensin-converting enzyme (ACE) — a zinc-dependent dicarboxypeptidase with two catalytic domains — plays a major part in blood pressure regulation by converting angiotensin I to angiotensin II. However, ACE cleaves many peptides besides angiotensin I and thereby affects diverse physiological functions, including renal development and male reproduction. In addition, ACE has a role in both innate and adaptive responses by modulating macrophage and neutrophil function — effects that are magnified when these cells overexpress ACE. Macrophages that overexpress ACE are more effective against tumours and infections. Neutrophils that overexpress ACE have an increased production of superoxide, which increases their ability to kill bacteria. These effects are due to increased ACE activity but are independent of angiotensin II. ACE also affects the display of major histocompatibility complex (MHC) class I and MHC class II peptides, potentially by enzymatically trimming these peptides. Understanding how ACE expression and activity affect myeloid cells may hold great promise for therapeutic manipulation, including the treatment of both infection and malignancy.

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“…Performance specification of RAS thus comes to evolve in terms of pathways of metabolism and also of cell survival and cell death pathway evolution. The use of antihypertensive agents targeting RAS, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can alter the incidence of renal cell carcinoma and also prolong patient survival [13] . It is further in terms of incremental activation that targeting pharmaceutics performs the significant roles for further transformation and this within a global scenario of cancer lesion maintenance.…”

Section: Internal Membranesmentioning

confidence: 99%

Proponent Specificity as Targeting Evolutionary Traits in Ras Isoform Mutability in Carcinogenesis

2018

Med One

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Distributional and re-distributional patterns of compartmentalization of RAS isoforms are core, persistently active abnormalities that are central/additional phenomena within mutable molecular structure and dysfunction in carcinogenesis. In such terms, ongoing transformations attributes, both within the plasmalemma and the internal membrane compartments, potentiate transformation, as further illustrated by sequestration of mutational forms of RAS. The incremental adaptation response of injured cells further conforms with the resultant dimensions of cooperating networks, rather than as linear pathways; these network organizations induce groups of neoplastic cells to further augment the effector end-target predispositions toward pre-carcinogenesis and carcinogenesis. RAS formulation is hence primarily an effector initiator and maintenance-inducing role-pattern formulator in carcinogenesis, as reflected in central metabolic pathways of cell growth promotion and proliferation.

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Renin angiotensin system deregulation as renal cancer risk factor (Review)

Cited by 44 publications

References 77 publications

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Telmisartan inhibits NSCLC A549 cell proliferation and migration by regulating the PI3K/AKT signaling pathway

Angiotensin-converting enzyme in innate and adaptive immunity

Proponent Specificity as Targeting Evolutionary Traits in Ras Isoform Mutability in Carcinogenesis

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