14-kilodalton growth hormone fragment; angiogenesis; growth hormone; metastasis; plasminogen activator inhibitor-1; tumor growth; Human Growth Hormone; Plasminogen Activator Inhibitor 1; Mice; Humans; Animals; Cell Proliferation; Human Growth Hormone/metabolism; Melanoma; Catalysis; Molecular Biology; Spectroscopy; Computer Science Applications; Physical and Theoretical Chemistry; Organic Chemistry; Inorganic Chemistry; General Medicine
Abstract :
[en] The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Shaker, Baraah Tariq ; Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates ; Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
Ismail, Asmaa Anwar; Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates ; Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
Salih, Rawan ; Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates ; Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
Hadj Kacem, Hassen ; Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates ; Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
Rahmani, Mohamed; Department of Molecular Biology and Genetics, College of Medicine & Health Sciences, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates ; Center for Biotechnology, Khalifa University, Abu Dhabi P.O. Box 127788, United Arab Emirates
Struman, Ingrid ; Université de Liège - ULiège > GIGA > GIGA Cancer - Molecular Angiogenesis Laboratory
Bajou, Khalid; Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates ; Human Genetics & Stem Cells Research Group, Research Institute of Sciences & Engineering, University of Sharjah, Sharjah 27272, United Arab Emirates
Language :
English
Title :
The 14-Kilodalton Human Growth Hormone Fragment a Potent Inhibitor of Angiogenesis and Tumor Metastasis.
Publication date :
17 May 2023
Journal title :
International Journal of Molecular Sciences
ISSN :
1661-6596
eISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
This study was funded by the Office of Research and Graduate Studies, competitive research grant number: 18021154066, and targeted grant number: 21021450105 from the University of Sharjah, Sharjah, UAE.
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