Killing Effect of Methionine Enkephalin on Melanoma in Vivo and in Vitro

Overview

Journal Oncol Rep

Specialty Oncology

Date 2017 Aug 30

PMID 28849104

Citations 7

Authors

Dong-Mei Wang

Xue Jiao

Nicolas P Plotnikoff

Noreen Griffin

Rui-Qun Qi

Xing-Hua Gao

Feng-Ping Shan

Affiliations

Soon will be listed here.

Abstract

Melanoma is a common cutaneous malignancy, that is also found in specific mucosal sites, and is associated with a poor prognosis. The aim of the present study was to investigate the cytotoxicity of methionine enkephalin (MENK) for B16 melanoma cells in vivo and in vitro. The results of the present study allowed our conclusion that MENK regulates the proliferation of B16 cells, causing cell cycle arrest in the G0/G1 phase and a decrease in the percentage of cells in the S and G2/M phases. Reverse transcription-quantitative polymerase chain reaction demonstrated that MENK increased opioid receptor expression in the B16 cells. Furthermore, the tumor volume and weight in the MENK-treated group were lower than those in the control group (NS) and MENK and naltrexone (NTX)-treated groups. MENK exerted both significant antitumor activity on the growth of B16 cells and a longer survival time in mice. The mice treated with MENK exhibited an increased ratio of CD4+ to CD8+ T cells as tested by flow cytometry (FCM), resulting in a ratio of 2.03 in the control group, 3.69 in the MENK-treated group, and 2.65 in the MENK and NTX group. Furthermore, a significant increase in plasma levels of IL-2, IFN-γ and TNF-α was revealed as assessed by ELISA. In conclusion, the results of the present study indicate that MENK has a cytotoxic effect on B16 melanoma cells in vitro and in vivo, and suggest a potential mechanism for these bioactivities. Therefore, we posit that MENK should be investigated, not only as a primary therapy for melanoma, but also as an adjuvant therapy in combination with chemotherapies.

Citing Articles

Enkephalins and Pain Modulation: Mechanisms of Action and Therapeutic Perspectives.

Garcia-Dominguez M Biomolecules. 2024; 14(8).

PMID: 39199314 PMC: 11353043. DOI: 10.3390/biom14080926.

Involvement of the Opioid Peptide Family in Cancer Progression.

Sanchez M, Rodriguez F, Covenas R Biomedicines. 2023; 11(7).

PMID: 37509632 PMC: 10377280. DOI: 10.3390/biomedicines11071993.

Wnt Signaling Pathway Collapse upon β-Catenin Destruction by a Novel Antimicrobial Peptide SKACP003: Unveiling the Molecular Mechanism and Genetic Activities Using Breast Cancer Cell Lines.

Selvarathinam K, Subramani P, Thekkumalai M, Vilwanathan R, Selvarajan R, Abia A Molecules. 2023; 28(3).

PMID: 36770598 PMC: 9920962. DOI: 10.3390/molecules28030930.

The Interplay between Tumour Microenvironment Components in Malignant Melanoma.

Amalinei C, Grigoras A, Lozneanu L, Caruntu I, Giusca S, Balan R Medicina (Kaunas). 2022; 58(3).

PMID: 35334544 PMC: 8953474. DOI: 10.3390/medicina58030365.

Scorpion Venom Antimicrobial Peptides Induce Caspase-1 Dependant Pyroptotic Cell Death.

Elrayess R, Mohallal M, Mobarak Y, Ebaid H, Haywood-Small S, Miller K Front Pharmacol. 2022; 12:788874.

PMID: 35082671 PMC: 8784870. DOI: 10.3389/fphar.2021.788874.

References

Fletcher J, Lalor S, Sweeney C, Tubridy N, Mills K . T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 2010; 162(1):1-11. PMC: 2990924. DOI: 10.1111/j.1365-2249.2010.04143.x. View

Zagon I, McLaughlin P . Endogenous opioid systems regulate growth of neural tumor cells in culture. Brain Res. 1989; 490(1):14-25. DOI: 10.1016/0006-8993(89)90425-3. View

Wang Q, Gao X, Yuan Z, Wang Z, Meng Y, Cao Y . Methionine enkephalin (MENK) improves lymphocyte subpopulations in human peripheral blood of 50 cancer patients by inhibiting regulatory T cells (Tregs). Hum Vaccin Immunother. 2014; 10(7):1836-40. PMC: 4186042. DOI: 10.4161/hv.28804. View

McLaughlin P, Zagon I . Modulation of human neuroblastoma transplanted into nude mice by endogenous opioid systems. Life Sci. 1987; 41(12):1465-72. DOI: 10.1016/0024-3205(87)90711-9. View

Wang D, Wang G, Yang J, Plotnikoff N, Griffin N, Han Y . Inhibition of the growth of human melanoma cells by methionine enkephalin. Mol Med Rep. 2016; 14(6):5521-5527. PMC: 5355750. DOI: 10.3892/mmr.2016.5941. View

Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M . Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med. 2007; 13(10):1173-5. PMC: 5114125. DOI: 10.1038/nm1651. View

Zagon I, McLaughlin P . Naltrexone modulates tumor response in mice with neuroblastoma. Science. 1983; 221(4611):671-3. DOI: 10.1126/science.6867737. View

Weir C, McNeill A, Hook S, Harvie M, La Flamme A, Le Gros G . Critical role of preproenkephalin in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2006; 179(1-2):18-25. DOI: 10.1016/j.jneuroim.2006.06.021. View

Quidville V, Segond N, Pidoux E, Cohen R, Jullienne A, Lausson S . Tumor growth inhibition by indomethacin in a mouse model of human medullary thyroid cancer: implication of cyclooxygenases and 15-hydroxyprostaglandin dehydrogenase. Endocrinology. 2004; 145(5):2561-71. DOI: 10.1210/en.2003-0915. View

10.

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

11.

Curtin J, Fridlyand J, Kageshita T, Patel H, Busam K, Kutzner H . Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005; 353(20):2135-47. DOI: 10.1056/NEJMoa050092. View

12.

Zagon I, Wu Y, McLaughlin P . Opioid growth factor inhibits DNA synthesis in mouse tongue epithelium in a circadian rhythm-dependent manner. Am J Physiol. 1994; 267(3 Pt 2):R645-52. DOI: 10.1152/ajpregu.1994.267.3.R645. View

13.

Li W, Chen W, Herberman R, Plotnikoff N, Youkilis G, Griffin N . Immunotherapy of cancer via mediation of cytotoxic T lymphocytes by methionine enkephalin (MENK). Cancer Lett. 2013; 344(2):212-22. DOI: 10.1016/j.canlet.2013.10.029. View

14.

Zagon I, McLaughlin P . Opioid antagonists inhibit the growth of metastatic murine neuroblastoma. Cancer Lett. 1983; 21(1):89-94. DOI: 10.1016/0304-3835(83)90087-3. View

15.

Shi V, Tran K, Patel F, Leventhal J, Konia T, Fung M . 100% Complete response rate in patients with cutaneous metastatic melanoma treated with intralesional interleukin (IL)-2, imiquimod, and topical retinoid combination therapy: results of a case series. J Am Acad Dermatol. 2015; 73(4):645-54. DOI: 10.1016/j.jaad.2015.06.060. View

16.

Hauser K, McLaughlin P, Zagon I . Endogenous opioids regulate dendritic growth and spine formation in developing rat brain. Brain Res. 1987; 416(1):157-61. DOI: 10.1016/0006-8993(87)91509-5. View

17.

Sassani J, Mc Laughlin P, Zagon I . The Yin and Yang of the Opioid Growth Regulatory System: Focus on Diabetes-The Lorenz E. Zimmerman Tribute Lecture. J Diabetes Res. 2016; 2016:9703729. PMC: 5039296. DOI: 10.1155/2016/9703729. View

18.

Xue M, Sun H, Cao Y, Wang G, Meng Y, Wang D . Mulberry leaf polysaccharides modulate murine bone-marrow-derived dendritic cell maturation. Hum Vaccin Immunother. 2015; 11(4):946-50. PMC: 4514181. DOI: 10.1080/21645515.2015.1011977. View

19.

Zagon I, Sassani J, Wu Y, McLaughlin P . The autocrine derivation of the opioid growth factor, [Met5]-enkephalin, in ocular surface epithelium. Brain Res. 1998; 792(1):72-8. DOI: 10.1016/s0006-8993(98)00123-1. View

20.

Zagon I, Sassani J, McLaughlin P . Reepithelialization of the human cornea is regulated by endogenous opioids. Invest Ophthalmol Vis Sci. 2000; 41(1):73-81. View