An intrinsic purine metabolite AICAR blocks lung tumour growth by targeting oncoprotein mucin 1 British Journal of Cancer

These data suggest that AICAR supplementation prevents sodium taurocholate-induced PALI in rats by increasing antioxidant activities in the liver. We explored the hypothesis that the molecular basis of AICAR in improving PALI is attributed to its anti-inflammatory capability. These observations confirm that AICAR treatment protects against PALI in sodium taurocholate-induced SAP rats, likely by inhibiting the inflammatory response in the liver. Approximately every 15 persons die of lung cancer in an hour in the US in 2022, accounting for 21% of all site cancer patients’ death hourly [38]. The death rate has dropped by three persons per hour compared to statistics in 2000 [39].

• The peptide received its name in the form of an abbreviation from the scientific name of a peptide extracted from the femoral muscle, which is called 5-aminoimidazole-4-carboxamidribofuranoside.
• It is suggested to play a role in the process of converting acetyl-CoA and malonyl-CoA, small molecules, into palmitate, a long-chain saturated fatty acid.
• Our RNA-seq data found no significant changes in PPARγ expression after AICAR treatment.
• Emerging evidence indicates that the activation of AMPK by AICAR attenuates high glucose-induced oxidative stress in rat cardiomyocytes (Shen et al., 2019).
• Although we are lacking in human clinical data, the existing evidence strongly points towards a net positive effect.
• Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by western blot.

However, the activity of AICAR on the cell growth and metastasis of prostate cancer has not been extensively studied. Herein we examine the effects of AICAR on the cell growth and metastasis of prostate cancer cells. Epithelial-mesenchymal transition (EMT)-related protein expression and AMPK/mTOR-dependent signaling axis were analyzed by https://www.ritmitica.it/new-study-reveals-effectiveness-of-sp-primobol-100/ western blot. In addition, we also tested the effect of AICAR on the chemosensitivity to docetaxel using MTT assay. Our results indicated that AICAR inhibits cell growth in prostate cancer cells, but not in non-cancerous prostate cells. These findings support AICAR as a potential therapeutic agent for the treatment of prostate cancer.

AICAR, short for 5-aminoimidazole-4-carboxamide ribonucleoside, is short peptide that plays a role in energy homeostasis and a number of metabolic pathways. AICAR plays a role in the regulation of insulin receptors and how muscle cells function with regards to insulin. AICAR is under active investigation for its cancer-fighting properties and for its ability to protect heart/cardiovascular tissue. Peptides are different, some accelerate the process of cell renewal, others increase immunity or optimize blood supply, improve vision or liver function, etc. Among them, there are those that increase metabolism and affect the muscles in the same way as playing sports for many hours.

AICAR was also posited to decrease the hepatic sterol regulatory element-binding protein 1c (SREBP-1c) and reduce fatty acid synthase (FAS) enzyme expression, reducing triglyceride synthesis in murine models’ livers. SREBP-1c is posited to be a protein apparently involved in lipid metabolism, primarily in liver tissues. It is a member of the SREBP family, which appears to be transcription factors that regulate the expression of genes required to synthesize cholesterol, fatty acids, and triglycerides. Therefore, it is possible that a decrease in SREBP-1c might lead to a reduction in fatty acid synthesis.

AICAR Research and Fertility

In all these tissues, it is considered to exert a potential net effect on lipogenesis and may inhibit cholesterol synthesis and ketogenesis. It may also modulate insulin secretion and skeletal muscle fatty acid oxidation with glucose uptake. Several energy deficit states may trigger the release of AMPK, like hypoxia or hypoglycemia. Besides AICAR targeting MUC1, our data suggest that AICAR also blocks JAK1 phosphorylation. A previous study showed that MUC1 interacts with STAT3 directly in breast cancer [30]. Our study is the first to report that AICAR treatment impairs MUC1 and JAK1 interaction.

Thus, in response to energy stress in the microenvironment of tumors, AMPK activation may lead to the reprogramming of cellular metabolism and elicits a metabolic checkpoint on the cell cycle through its action on mTORC1, p53 and other modulators for cell growth and survival. The ability to control inflammation could reduce the progression of vascular disease, including atherosclerosis. Research in rabbit models of atherosclerosis indicated that AICAR suppression vascular smooth muscle proliferation. This is not only an important component of cardiovascular disease, but is also one of the reasons that cardiac stents fail over time.

AICAR Prevents SAP-Induced Hepatic Inflammation in a Sodium Taurocholate-Induced SAP Rat Model

As you can clearly see, there’s an awful lot of speculation behind AICAR’s endurance-boosting benefits and not a lot of hard data in human subjects. The same holds for glucose oxidation as well, which is crucial for normal blood sugar levels. It first rose to prominence in the late 80s and early 90s as a form of heart protection during surgery via increased blood flow. It’s important to note that while AICAR has shown promise in various preclinical studies and animal models, its use in humans remains a subject of research and debate. AICAR is not approved for medical use in many countries, and its safety and efficacy in humans are not fully established.

The peptide received its name in the form of an abbreviation from the scientific name of a peptide extracted from the femoral muscle, which is called 5-aminoimidazole-4-carboxamidribofuranoside. AICAR provides an almost 50% increase in stamina and the rate of consumption of fats (lipids), which are known to serve as a fuel energy source. All animal research complied with protocols approved by the Institutional Animal Care and Use committees (IACUC) from BIDMC, Yale University, and UCF. EGFR T790M-L858R (EGFR TL)/CCSP-rtTA bi-transgenic mice and tetO-Cre transgenic mice were previously described [63]. To induce EGFR TL expression, 6-week-old female mice were fed a doxycycline (Dox) diet (Envigo) continuously for 0–14 weeks (EG0, EG1, EG2, EG10, EG14). Among these mice, one group fed a Dox diet for 8 weeks was followed by a regular diet for 2 weeks (EG8OFF2).

Pierce protease and phosphatase inhibitor mini tablets (Lot #WD319834, Cat #A32959) were from Thermo Fisher Scientific and utilised for protein extraction. No, athletes cannot get a TUE for AICAR because it is not approved for use in humans anywhere in the world. AICAR is not available as a medication, so your doctor should not prescribe it for you under any circumstance. Numerous doping detection methods (here, here, here, here, and here) have not only established a baseline for endogenous AICAR production, but can also detect high levels of AICAR long after you’ve given your blood sample.

One reason for this decrease was the administration of widespread tyrosine kinase inhibitors (TKIs) that block mutant EGFR signalling as the first-line therapy in patients harbouring EGFR mutations [40,41,42]. In a preclinical setting, introducing mutant EGFR into mouse alveolar epithelial cells induces malignant phenotypes comparable to human lung adenocarcinoma. It demonstrates objective responses to EGFR induction or inactivation with changed protein expression for phosphorylated (p-EGFR) and total EGFR [43, 44]. Even though most patients respond well to these EGFR TKIs with prolonged survival, non-specific tissue distribution has limited their application. Consequently, the actual osimertinib concentration in lung tumours is below the effective dose by lysosomal sequestration with cysteine proteases, leading to acquired drug resistance [47, 48]. Compared to inactivating EGFR by osimertinib, degrading oncoprotein is becoming an alternative strategy for anticancer therapy that might decrease the incidence of drug resistance [49,50,51].