AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review

Thus, we have found a new compound to block MUC1-CT in lung cancer cells that might apply to many other types of cancers. The anticancer effects of AICAR are mediated by the activation of AMPK and reduction of mTOR signaling 31. AICAR have been reported to enhance the efficacy of conventional chemotherapeutic agents in the treatment of local and metastatic nasopharyngeal carcinoma (NPC) 32. AMPK activators such as AICAR provide a therapeutic strategy for hematological malignancies 33, 34. First, AICAR can induce apoptosis in B-cell chronic lymphocytic leukemia cells 35 and kill chronic myelogenous leukemia (CML) cells through PKC-dependent induction of autophagic cell death 36.

• By dampening inflammatory pathways, it mitigates the risk of plaque formation and arterial blockages 6.
• Although its precise cause remains elusive, dysfunction of the retinal pigment epithelium (RPE) and dysregulation of complement have been implicated in its pathogenesis.
• Thus, the effects of acute exercise on MnSOD and OSCP deacetylation may vary across different experimental models and organisms.
• Krabbe disease (KD) is an inherited neurological disorder caused by the deficiency of galactocerebrosidase activity resulting in accumulation of psychosine, which leads to energy depletion, loss of oligodendrocytes, induction of gliosis, and inflammation by astrocytes in CNS.
• The supernatant was replaced with fresh culture medium containing TNF-α, AICAR and metformin.

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Documented in vitro assays usually focus on a specific compound or a specific parameter using a relatively large sample size (11–13,17). It highlights NAD+’s involvement in cellular energy production, DNA repair, and sirtuin activation, which contribute to improved metabolic efficiency, energy levels, and cognitive function. AICAR and NAD+ potential benefits for diabetes management and overall health are also discussed, emphasizing its significance in promoting longevity and well-being. Explore the benefits of AICAR Nasal Spray Peptide in this blog, and its role in enhancing cellular energy by activating the AMPK pathway. Discover potential health benefits, including improved metabolic function, cardiovascular health, neuroprotection, and anti-inflammatory effects, making it a promising therapeutic tool in the future for various health conditions. When AMPK is activated by AICAR, it influences several inflammatory pathways, leading to a reduction in inflammation.

AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD

Furthermore, AICAR enhances lipid metabolism by increasing fatty acid oxidation, which helps lower triglyceride levels and prevent the accumulation of harmful lipids in the bloodstream. This process aids in maintaining a healthy lipid profile, crucial for cardiovascular health 5. By mimicking exercise effects, AICAR offers therapeutic potential for individuals unable to engage in physical activity, supporting cardiovascular health and metabolic disease management. Concurrently, by enhancing fatty acid oxidation, AMPK reduces lipid accumulation, contributing to lower body fat levels. These metabolic adjustments make AICAR a promising candidate for treating metabolic disorders such as diabetes and obesity. The ovarian cycle is characterized by repeating patterns of cellular proliferation and differentiation that accompany follicular development as well as ovulation under the appropriate gonadotropin stimulation.

We also studied the effect of AICAR and NAM treatment on the differentiation potential of MSCs after a long-term in vitro culture using adipogenic and osteogenic induction media. We observed that higher levels of matrix mineralization were achieved following treatment with AICAR and NAM. Noticeably, the treatment of cells with simultaneous AICAR+NAM significantly increased the calcium deposition (Fig.4a). Moreover, the expression of the markers of osteogenesis—Runx-2, osteopontin, and ALP—was enhanced in AICAR+NAM-, AICAR only-, and NAM only-treated cells compared to the untreated cells (Fig. 4b).

A comparison of the potency of alternative schedules of administration of the modalities AICAR and X-rays revealed that the most effective kill of PC3 clonogens was achieved when treatments were administered simultaneously (Figure 2A). After simultaneous administration, AICAR enhanced the clonogenic kill of PC3 cells induced by a range of doses (1 to 4 Gy) of radiation (Figure 2B). The surviving fractions following radiation treatment at a dose of 2 Gy (SF2) were 0.45 ± 0.03, 0.30 ± 0.02 and 0.25 ± 0.04 for 0, 0.5 and 1 mM AICAR, respectively, giving dose enhancement ratios (DER) of 1.86 ± 0.15 and 2.09 ± 0.31 for 0.5 and 1 mM AICAR, respectively. Moreover, combination index analysis (Figure 2C) indicated that at all toxicity levels, the combination of AICAR and radiation resulted in a greater than additive enhancement of clonogenic kill of PC3 cells, indicated by CI values less than 1. The anti-diabetic drug metformin may sensitize cells to radiation by acting as an AMPK activator. We observed that the enhancing effect of 0.5 mM AICAR on clonogenic killing activity of radiation was similar to that of 5 mM metformin (Figure 2D).

Figure 1.

Our data calls for high-throughput screening of various cancer cell lines in combination treatment with AICAR, JAK, or EGFR inhibitors. Intratumoral and intertumoral heterogeneity in MUC1 expression across https://micontactoweb.com/steroids-understanding-their-use-and-impact-77/ diverse types of lung cancer will challenge the strategy of applying AICAR in targeting MUC1-expressing cells. Our study was also limited to MUC1–JAK1 interaction in the same type of lung cancer cells.