Tyr-Gly-Gly-Phe-Met-OH (Met-Enkephalin) is an endogenous opioid that acts as the δ opioid receptor with an EC50 value of 1.03nM[1]. Tyr-Gly-Gly-Phe-Met-OH can induce changes in macrophage function, stimulate the phagocytic activity of macrophages, and enhance the production of cytokines by macrophages[2]. Tyr-Gly-Gly-Phe-Met-OH can serve as a biomarker for stress-induced changes in the brain in mouse models[3].
In vitro, Tyr-Gly-Gly-Phe-Met-OH treatment (0.1nM) for 24h combined with IFN-γ caused an increase in IL-6 release from the cultured murine macrophages[4]. Tyr-Gly-Gly-Phe-Met-OH (0.1nM; 1h) enhanced the H2O2 release in macrophages pretreated with 25nM phorbol myristate acetate (PMA) [5]. Treatment with 12.5mg/ml Tyr-Gly-Gly-Phe-Met-OH for 48 hours significantly inhibited the proliferation of B16 cells and induced cell cycle arrest[6].
In vivo, Tyr-Gly-Gly-Phe-Met-OH treatment via intraperitoneal injection at a dose of 10mg/kg/day for 28 days significantly reduced the tumor volume in mice with the xenograft of MG-63 cells, without affecting body weight [7]. Tyr-Gly-Gly-Phe-Met-OH treatment (20mg/kg/day; i.p.) for 21 days inhibited tumor growth by enhancing the immunogenicity and recognition of MC38 cells in colorectal tumor-bearing mice and efficiently suppressed the mRNA expression of genes encoding inflammatory cytokines in the tumor tissues of mice [8].
References:
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[2]Zhao D, Plotnikoff N, Griffin N, et al. Methionine enkephalin, its role in immunoregulation and cancer therapy[J]. International immunopharmacology, 2016, 37: 59-64.
[3] Nabeshima T, Katoh A, Wada M, et al. Stress-induced changes in brain Met-enkephalin, Leu-enkephalin and dynorphin concentrations[J]. Life sciences, 1992, 51(3): 211-217.
[4] Kowalski J, Makowiecka K, Belowski D, et al. Augmenting effect of methionine-enkephalin on interleukin-6 production by cytokine-stimulated murine macrophages[J]. Neuropeptides, 2000, 34(3-4): 187-192.
[5] Stanojević S, Vujić V, Mitić K, et al. Methionine-enkephalin modulation of hydrogen peroxide (H2O2) release by rat peritoneal macrophages involves different types of opioid receptors[J]. Neuropeptides, 2008, 42(2): 147-158.
[6] Wang D M, Jiao X, Plotnikoff N P, et al. Killing effect of methionine enkephalin on melanoma in vivo and in vitro[J]. Oncology Reports, 2017, 38(4): 2132-2140.
[7] Huang H, Wang X, Zhang S, et al. In vitro and in vivo killing effects of methionine enkephalin on osteosarcoma[J]. International Immunopharmacology, 2023, 125: 111226.
[8] Wang X, Li S, Yan S, et al. Methionine enkephalin inhibits colorectal cancer by remodeling the immune status of the tumor microenvironment[J]. International Immunopharmacology, 2022, 111: 109125.