GLP-1 receptor agonist as treatment for cancer as well as diabetes: beyond blood glucose control

Nomiyama, Takashi; Yanase, Toshihiko

doi:10.1080/17446651.2016.1191349

Cited by 4 publications

(3 citation statements)

References 73 publications

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“…The potential links between obesity and carcinogenesis are exemplified by the finding that GLP-1R agonists can inhibit cancer development as well as type-2 diabetes mellitus. Cancer is one of the main causes of death in patients with type-2 diabetes ( Nomiyama and Yanase, 2016 ; Yorifuji et al, 2016 ). GLP-1 agonists can promote cell apoptosis in some tumors and cell lines, thus exhibiting anti-cancer activity, in some cases by inhibiting glycogen synthase kinase-3 (GSK-3) ( Koehler et al, 2011 ).…”

Section: Obesity and Cancermentioning

confidence: 99%

Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

2018

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Existing explanations of obesity-associated cancer emphasise direct mutagenic effects of dietary components or hormonal imbalance. Some of these hypotheses are reviewed briefly, but recent evidence suggests a major role for chronic inflammation in cancer risk, possibly involving dietary content. These ideas include the inflammation-induced activation of the kynurenine pathway and its role in feeding and metabolism by activation of the aryl hydrocarbon receptor (AHR) and by modulating synaptic transmission in the brain. Evidence for a role of the kynurenine pathway in carcinogenesis then provides a potentially major link between obesity and cancer. A second new hypothesis is based on evidence that serine proteases can deplete cells of the tumour suppressors Deleted in Colorectal Cancer (DCC) and neogenin. These enzymes include mammalian chymotryptic proteases released by pro-inflammatory neutrophils and macrophages. Blood levels of chymotrypsin itself increase in parallel with food intake. The mechanistically similar bacterial enzyme subtilisin is widespread in the environment, animal probiotics, meat processing and cleaning products. Simple public health schemes in these areas, with selective serine protease inhibitors and AHR antagonists and could prevent a range of intestinal and other cancers.

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Section: Obesity and Cancermentioning

confidence: 99%

Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

2018

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“…The mechanism-of-action of GLP-1 on cancer is still under elucidation, as we described in a previous review 24 . Although some data have shown a risk of carcinogenesis from GLP-1R agonist use, there is no evidence in randomized controlled trials that GLP-1R agonists increase cancer onset or death.…”

Section: Discussionmentioning

confidence: 98%

Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression

Shigeoka

Nomiyama

Kawanami

et al. 2020

J of Diabetes Invest

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Aims/Introduction Incretin therapy is a common treatment for type 2 diabetes mellitus. We have previously reported an anti‐prostate cancer effect of glucagon‐like peptide‐1 receptor (GLP‐1R) agonist exendin‐4. The attenuation of cell proliferation in the prostate cancer cell line was dependent on GLP‐1R expression. Here, we examined the relationship between human prostate cancer severity and GLP‐1R expression, as well as the effect of forced expression of GLP‐1R using a lentiviral vector. Materials and Methods Prostate cancer tissues were extracted by prostatectomy and biopsy. GLP‐1R was overexpressed in ALVA‐41 cells using a lentiviral vector (ALVA‐41‐GLP‐1R cells). GLP‐1R expression was detected by immunohistochemistry and quantitative polymerase chain reaction. Cell proliferation was examined by growth curves and bromodeoxyuridine incorporation assays. Cell cycle distribution and regulators were examined by flow cytometry and western blotting. In vivo experiments were carried out using a xenografted model. Results GLP‐1R expression levels were significantly inversely associated with the Gleason score of human prostate cancer tissues. Abundant GLP‐1R expression and functions were confirmed in ALVA‐41‐GLP‐1R cells. Exendin‐4 significantly decreased ALVA‐41‐GLP‐1R cell proliferation in a dose‐dependent manner. DNA synthesis and G1‐to‐S phase transition were inhibited in ALVA‐41‐GLP‐1R cells. SKP2 expression was decreased and p27Kip1 protein was subsequently increased in ALVA‐41‐GLP‐1R cells treated with exendin‐4. In vivo experiments carried out by implanting ALVA‐41‐GLP‐1R cells showed that exendin‐4 decreased prostate cancer growth by activation of GLP‐1R overexpressed in ALVA41‐GLP‐1R cells. Conclusions Forced expression of GLP‐1R attenuates prostate cancer cell proliferation by inhibiting cell cycle progression in vitro and in vivo. Therefore, GLP‐1R activation might be a potential therapy for prostate cancer.

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“…The impact of GLP-1R agonists such as semaglutide extends beyond diabetes control: they play a multifaceted role in regulating blood glucose levels by reducing hunger, moderating food intake, and managing body weight [36]. Notably, GLP-1R agonists inhibit cancer progression in some malignant tumors [37][38][39][40].…”

Section: The Treatment Complexitiesmentioning

confidence: 99%

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

Ibrahim,

Arabi

et al. 2024

Cancer Metastasis Rev

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Glucagon-like peptide-1 receptor (GLP-1R) agonists have garnered significant attention for their therapeutic potential in addressing the interconnected health challenges of diabetes, obesity, and cancer. The role of GLP-1R in type 2 diabetes mellitus (T2DM) is highlighted, emphasizing its pivotal contribution to glucose homeostasis, promoting β-cell proliferation, and facilitating insulin release. GLP-1R agonists have effectively managed obesity by reducing hunger, moderating food intake, and regulating body weight. Beyond diabetes and obesity, GLP-1R agonists exhibit a multifaceted impact on cancer progression across various malignancies. The mechanisms underlying these effects involve the modulation of signaling pathways associated with cell growth, survival, and metabolism. However, the current literature reveals a lack of in vivo studies on specific GLP-1R agonists such as semaglutide, necessitating further research to elucidate its precise mechanisms and effects, particularly in cancer. While other GLP-1R agonists have shown promising outcomes in mitigating cancer progression, the association between some GLP-1R agonists and an increased risk of cancer remains a topic requiring more profound investigation. This calls for more extensive research to unravel the intricate relationships between the GLP-1R agonist and different cancers, providing valuable insights for clinicians and researchers alike.

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GLP-1 receptor agonist as treatment for cancer as well as diabetes: beyond blood glucose control

Cited by 4 publications

References 73 publications

Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

Obesity and Cancer: Existing and New Hypotheses for a Causal Connection

Activation of overexpressed glucagon‐like peptide‐1 receptor attenuates prostate cancer growth by inhibiting cell cycle progression

The effect of GLP-1R agonists on the medical triad of obesity, diabetes, and cancer

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