Evaluation of role of telmisartan in combination with 5-fluorouracil in gastric cancer cachexia

Sukumaran, Shreesha; Patel, Hetal; Patel, Bhoomika M.

doi:10.1016/j.lfs.2016.04.029

Cited by 17 publications

(5 citation statements)

References 46 publications

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“…Our results revealed that a slightly higher dose of telmisartan also markedly suppressed the growth of subcutaneous CCA tumors in athymic nude mice. These data ( in vivo study) suggest that the use of telmisartan in CCA treatment may be effective in combination therapy with other anticancer drugs ( 38 ).…”

Section: Discussionmentioning

confidence: 93%

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Samukawa

Fujihara

Oura

et al. 2017

International Journal of Oncology

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Cholangiocarcinoma (CCA) is at an advanced stage at the time of its diagnosis, and developing a more effective treatment of CCA would be desirable. Angiotensin II type 1 (AT1) receptor blocker (ARB), telmisartan may inhibit cancer cell proliferation, but the mechanisms by which telmisartan affects various cancers remain unknown. In this study, we evaluated the effects of telmisartan on human CCA cells and to assess the expression of microRNAs (miRNAs). We studied the effects of telmisartan on CCA cells using two cell lines, HuCCT-1 and TFK-1. In our experiments, telmisartan inhibited the proliferation of HuCCT-1 and TFK-1 cells. Additionally, telmisartan induced G0/G1 cell cycle arrest via blockade of the G0 to G1 cell cycle transition. Notably, telmisartan did not induce apoptosis in HuCCT-1 cells. This blockade was accompanied by a strong decrease in cell cycle-related protein, especially G1 cyclin, cyclin D1, and its catalytic subumits, Cdk4 and Cdk6. Telmisartan reduced the phosphorylation of EGFR (p-EGFR) and TIMP-1 by using p-RTK and angiogenesis array. Furthermore, miRNA expression was markedly altered by telmisartan in HuCCT-1. Telmisartan inhibits tumor growth in CCA xenograft model in vivo. In conclusion, telmisartan was shown to inhibit human CCA cell proliferation by inducing cell cycle arrest.

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Section: Discussionmentioning

confidence: 93%

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Samukawa

Fujihara

Oura

et al. 2017

International Journal of Oncology

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“…In transwell assays, telmisartan significantly inhibited the invasion and migration of A549. Telmisartan is a specific AT1R blocker, which has the strongest binding affinity for AT1R in ARBs (16,33). It has previously been reported that Ang II can potentiate breast cancer cell migration (25).…”

Section: Discussionmentioning

confidence: 99%

“…AT1R mediates the main functions of Ang II, including tumor growth and angiogenesis (15). Treatment with telmisartan, a specific AT1R blocker, leads to apoptosis and the inhibition of cell cycle progression in cancer cells (16,17). It has been reported that telmisartan has anti-proliferative activity in prostate and renal cell cancer (18,19); however, there are few relevant reports on the anti-proliferative activity of telmisartan in NSCLC cells (20).…”

Section: Introductionmentioning

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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“…46 Angiotensin receptor blockers can also be used in the treatment of cachexia. Thus, one of this compounds, Telmisartan, can be used as an add-on therapy with 5-fluorouracil, 47 or cisplatin, 48 or other traditional chemotherapeutic agents. Telmisartan inhibits TNF-α-induced IL-6 expression at the transcriptional level through the activation of PPAR-γ.…”

Section: Drugs Acting On Other Metabolic Targetsmentioning

confidence: 99%

Therapeutic strategies against cancer cachexia

Argilés¹,

López‐Soriano²,

Stemmler³

et al. 2019

Eur J Transl Myol

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Cancer cachexia has two main components: anorexia and metabolic alterations. The main changes associated with the development of this multi-organic syndrome are glucose intolerance, fat depletion and muscle protein hypercatabolism. The aim of this paper is to review the more recent therapeutic approaches designed to counteract the wasting suffered by the cancer patient with cachexia. Among the most promising approaches we can include the use of ghrelin agonists, beta-blockers, beta-adrenergic agonists, androgen receptor agonists and anti-myostatin peptides. The multi-targeted approach seems essential in these treatments, which should include the combination of both nutritional support, drugs and a suitable program of physical exercise, in order to ameliorate both anorexia and the metabolic changes associated with cachexia. In addition, another very important and crucial aspect to be taken into consideration in the design of clinical trials for the treatment of cancer cachexia is to staging cancer patients in relation with the degree of cachexia, in order to start as early as possible this triple approach in the course of the disease, even before the weight loss can be detected.

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Evaluation of role of telmisartan in combination with 5-fluorouracil in gastric cancer cachexia

Cited by 17 publications

References 46 publications

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest

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

Therapeutic strategies against cancer cachexia

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