Inhibition of the growth of human melanoma cells by methionine enkephalin

Abstract

Melanoma is an aggressive cancer, the incidence of which is increasing worldwide. Limited therapies are currently available, particularly following metastasis. The aim of the present study was to investigate the inhibiting effect of methionine enkephalin (MENK) on human melanoma via opioid receptors. The results of the present study revealed that MENK markedly regulates the proliferation of A375 cells, causing cell cycle arrest in G0/G1 phase and a decrease in the percentage of cells in S and G2/M phases. Reverse transcription-quantitative polymerase chain reaction demonstrated that MENK treatment increased opioid receptor expression in A375 cells. Furthermore, the expression level of survivin, an inhibitory apoptotic protein, was 1.1% of the level in the control group in the MENK group following 48 h of treatment. In conclusion, the results of the present study revealed, to the best of our knowledge for the first time, that MENK may inhibit growth and induce apoptosis of A375 cells, and describes a potential mechanism underlying these effects. Therefore, MENK should be investigated as a primary therapy for human melanoma cancer and as an adjuvant to other chemotherapies. Further studies are required to develop an optimal strategy for the use of MENK for the treatment of human cancers.

The novel mechanism of anticancer effect on gastric cancer through inducing G0/G1 cell cycle arrest and caspase-dependent apoptosis in vitro and in vivo by methionine enkephalin

“…Published data suggest that MENK also has an antiviral role during influenza 36 and HIV infections. 37 Moreover, MENK has significant immunotherapeutic activity against tumors in vivo, including ovarian, 21 pancreatic, 38 and head–neck cancers, 39 and can inhibit or delay tumor cell proliferation directly in vitro through cell apoptosis and/or cell cycle arrest, as reported in studies examining human melanoma, 10 triple-negative breast cancer, 24 and hepatoblastoma cancer cells. 40 The results from all these studies support these bioactivities mediated by OGFr ligation.…”

“… 5 The OGF not only has neuroendocrine 9 and immune regulation activity, but also has direct antitumor activity following binding to opioid receptors. 2 , 6 , 10 – 18 Naltrexone (NTX), an opioid receptor antagonist, can inhibit the effects of MENK during co-incubation, supporting its role in the bioactivity of MENK. 2 Data from previously published results from our laboratory indicated that MENK, in a dose-dependent manner, can inhibit tumor growth in vivo and in vitro.…”

“… 2 Data from previously published results from our laboratory indicated that MENK, in a dose-dependent manner, can inhibit tumor growth in vivo and in vitro. These studies have focused on human melanoma cancer, 10 human pancreatic cancer, 19 human ovarian cancer, 20 , 21 thyroid follicular cell-derived cancers, 22 human hepatocellular cancer, 23 and triple-negative breast cancer. 24 Our team has also demonstrated that MENK can inhibit human melanoma cancer cell growth by inducing cell apoptosis and cell cycle arrest in G0/G1 phase.…”

“… 24 Our team has also demonstrated that MENK can inhibit human melanoma cancer cell growth by inducing cell apoptosis and cell cycle arrest in G0/G1 phase. 10 …”

Killing effect of methionine enkephalin on melanoma in vivo and in vitro

“…In our previous study, we demonstrated that MENK alone or in combination with IL-2 or IFN-γ, respectively strengthened the pathway between dendritic cells (DCs) and CD4 + T cells, and induced maturation of DCs with higher production of IL-12 ( 26 ). MENK was found to inhibit the growth and induce apoptosis of A375 cells ( 27 ). In the present study, we made the unique discovery that MENK not only can inhibit the proliferation and metastasis of B16 cells directly, but also can indirectly kill B16 cells by stimulating lymphocyte subsets and cytokine secretion to achieve the therapeutic goal.…”