Evaluation of 2‑methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma

Hrgovic,Igor; Kleemann,Johannes; Doll,Monika; Loquai,Carmen; Weid,Florian; Louwen,Frank; Zoeller,Nadja; Kippenberger,Stefan; Kaufmann,Roland; Meissner,Markus

doi:10.3892/mco.2021.2303

July-2021 Volume 15 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2021 Volume 15 Issue 1

Full Size Image

Article

Evaluation of 2‑methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma

Authors:
- Igor Hrgovic
- Johannes Kleemann
- Monika Doll
- Carmen Loquai
- Florian Weid
- Frank Louwen
- Nadja Zoeller
- Stefan Kippenberger
- Roland Kaufmann
- Markus Meissner
View Affiliations / Copyright

Affiliations: Department of Dermatology, Venereology and Allergology, Goethe University, D‑60590 Frankfurt, Germany, Department of Dermatology, University Medical Centre Mainz, D‑55131 Mainz, Germany, Department of Gynaecology and Obstetrics, Goethe University, D‑60590 Frankfurt, Germany
Article Number: 141
|
Published online on: May 23, 2021

https://doi.org/10.3892/mco.2021.2303
Expand metrics +

Abstract

Experimental findings indicated that 2‑methoxyestradiol (2‑ME), an endogenous metabolite of 17β‑estradiol, may exhibit anti‑tumorigenic properties in various types of tumour, such as melanoma and endometrial carcinoma. In patients with endometrial cancer, the serum levels of 2‑ME are decreased compared with those in healthy controls, and this finding has been associated with a poor outcome. The aim of the present study was to examine whether the serum levels of 2‑ME are decreased in patients with melanoma, and whether this decrease may be correlated with disease stage and, therefore, serve as a prognostic indicator. ELISA was used to detect serum levels of 2‑ME in patients with stage I‑IV malignant melanoma (MM). A cohort of 78 patients with MM was analysed, along with 25 healthy controls, among whom 15 were women in the second trimester of pregnancy (positive control). As expected, significantly elevated levels of serum 2‑ME were observed in pregnant control patients compared with those in patients with MM and healthy controls. There was no observed correlation between 2‑ME serum levels in patients with MM and disease stage, tumour thickness, lactate dehydrogenase or S100 calcium‑binding protein B levels. In addition, the 2‑ME levels of patients with MM did not differ significantly from those of normal healthy controls. Overall, the findings of the present study indicated that the 2‑ME serum levels in patients with MM were not decreased, and there was no correlation with early‑ or advanced‑stage disease. Therefore, in contrast to published results on endometrial cancer, endogenous serum 2‑ME levels in MM were not found to be correlated with tumour stage and did not appear to be a suitable prognostic factor in MM.

View Figures

View References

1	Barnes B, Kraywinkel K, Nowossadeck E, Schönfeld I, Starker A, Wienecke A and Wolf U: Bericht zum Krebsgeschehen in Deutschland 2016. Robert Koch-Institut, Berlin, 2016.
2	Malissen N and Grob JJ: Metastatic melanoma: Recent therapeutic progress and future perspectives. Drugs. 78:1197–1209. 2018.PubMed/NCBI View Article : Google Scholar
3	Amin MB, Edge S, Greene F, Byrd DR, Brookland RK, Washington MK, Gershenwald JE, Compton CC, Hess KR, Sullivan DC (eds), et al: AJCC Cancer Staging Manual. Springer International Publishing, New York, NY, 2017.
4	Mocellin S, Zavagno G and Nitti D: The prognostic value of serum S100B in patients with cutaneous melanoma: A meta-analysis. Int J Cancer. 123:2370–2376. 2008.PubMed/NCBI View Article : Google Scholar
5	Karagiannis P, Fittall M and Karagiannis SN: Evaluating biomarkers in melanoma. Front Oncol. 4(383)2014.PubMed/NCBI View Article : Google Scholar
6	Perez-Sepulveda A, Espana-Perrot PP, Norwitz ER and Illanes SE: Metabolic pathways involved in 2-methoxyestradiol synthesis and their role in preeclampsia. Reprod Sci. 20:1020–1029. 2013.PubMed/NCBI View Article : Google Scholar
7	Shen Z, Wu Y, Chen X, Chang X, Zhou Q, Zhou J, Ying H, Zheng J, Duan T and Wang K: Decreased maternal serum 2-methoxyestradiol levels are associated with the development of preeclampsia. Cell Physiol Biochem. 34:2189–2199. 2014.PubMed/NCBI View Article : Google Scholar
8	Parada-Bustamante A, Valencia C, Reuquen P, Diaz P, Rincion-Rodriguez R and Orihuela PA: Role of 2-methoxyestradiol, an endogenous estrogen metabolite, in health and disease. Mini Rev Med Chem. 15:427–438. 2015.PubMed/NCBI View Article : Google Scholar
9	Huang XX, Wang RX, Lin Q, Chen W, Pan Y, Wang SQ, Weng ZL and Huang WP: Inhibitory effects of 2-methoxyestradiol on cell growth and invasion in human bladder cancer T-24 cells. Pharmazie. 72:87–90. 2017.PubMed/NCBI View Article : Google Scholar
10	Zhe N, Chen S, Zhou Z, Liu P, Lin X, Yu M, Cheng B, Zhang Y and Wang J: HIF-1α inhibition by 2-methoxyestradiol induces cell death via activation of the mitochondrial apoptotic pathway in acute myeloid leukemia. Cancer Biol Ther. 17:625–634. 2016.PubMed/NCBI View Article : Google Scholar
11	Massaro RR, Faiao-Flores F, Rebecca VW, Sandri S, Alves-Fernandes DK, Pennacchi PC, Smalley KS and Maria-Engler SS: Inhibition of proliferation and invasion in 2D and 3D models by 2-methoxyestradiol in human melanoma cells. Pharmacol Res. 119:242–250. 2017.PubMed/NCBI View Article : Google Scholar
12	Kato S, Sadarangani A, Lange S, Delpiano AM, Vargas M, Brañes J, Carvajal J, Lipkowitz S, Owen GI and Cuello MA: 2-methoxyestradiol mediates apoptosis through caspase-dependent and independent mechanisms in ovarian cancer cells but not in normal counterparts. Reprod Sci. 15:878–894. 2008.PubMed/NCBI View Article : Google Scholar
13	Ricker JL, Chen Z, Yang XP, Pribluda VS, Swartz GM and Van Waes C: 2-methoxyestradiol inhibits hypoxia-inducible factor 1alpha, tumor growth, and angiogenesis and augments paclitaxel efficacy in head and neck squamous cell carcinoma. Clin Cancer Res. 10:8665–8673. 2004.PubMed/NCBI View Article : Google Scholar
14	El Naga RN, El-Demerdash E, Youssef SS, Abdel-Naim AB and El-Merzabani M: Cytotoxic effects of 2-methoxyestradiol in the hepatocellular carcinoma cell line HepG2. Pharmacology. 84:9–16. 2009.PubMed/NCBI View Article : Google Scholar
15	Solum EJ, Akselsen OW, Vik A and Hansen TV: Synthesis and pharmacological effects of the anti-cancer agent 2-methoxyestradiol. Curr Pharm Des. 21:5453–5466. 2015.PubMed/NCBI View Article : Google Scholar
16	Zhao H, Jiang Y, Liu Y, Yun C and Li L: Endogenous estrogen metabolites as biomarkers for endometrial cancer via a novel method of liquid chromatography-mass spectrometry with hollow fiber liquid-phase microextraction. Horm Metab Res. 47:158–164. 2015.PubMed/NCBI View Article : Google Scholar
17	Dobos J, Timar J, Bocsi J, Burián Z, Nagy K, Barna G, Peták I and Ladányi A: In vitro and in vivo antitumor effect of 2-methoxyestradiol on human melanoma. Int J Cancer. 112:771–776. 2004.PubMed/NCBI View Article : Google Scholar
18	Newman SP, Leese MP, Purohit A, James DR, Rennie CE, Potter BV and Reed MJ: Inhibition of in vitro angiogenesis by 2-methoxy- and 2-ethyl-estrogen sulfamates. Int J Cancer. 109:533–540. 2004.PubMed/NCBI View Article : Google Scholar

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Evaluation of 2‑methoxyestradiol serum levels as a potential prognostic marker in malignant melanoma

This article is mentioned in:

Abstract

Figure 1

Related Articles