Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights

Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights Publisher Pubmed

Chamani R¹ ; Asghari SM¹ ; Alizadeh AM² ; Eskandari S¹ ; Mansouri K³ ; Khodarahmi R³ ; Taghdir M⁴ ; Heidari Z¹ ; Gorji A⁵ ; Aliakbar A⁶ ; Ranjbar B⁴ ; Khajeh K⁷

Show Affiliations

1. Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
2. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran
3. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
4. Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
5. Epilepsy Research Center, University of Munster, Munster, Germany
6. Department of Chemistry, Faculty of Sciences, University of Guilan, Rasht, Iran
7. Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Source: Vascular Pharmacology Published:2015

Abstract

Although considerable effort has been devoted to understanding the molecular mechanism of endostatin's anti-cancer activity, the role of its Zn bound N-terminal loop has not been completely clarified. To investigate whether Zn binding or the N-terminal loop is involved in the anti-cancer properties of endostatin, we compared the structure and biological activity of a native Zn binding endostatin peptide (ES-Zn) with three variants: a Zn free variant (ES), a variant containing both a Zn binding site and a disulfide bond (ES-SSZn), and a variant including a disulfide loop but incapable of Zn binding (ES-SS). Spectroscopic studies indicated that ES-Zn and ES-SS consist of random coil and β structures, whereas ES-SSZn and ES fold into random coils. Theoretical analysis proposed that ES-Zn and ES-SS have a similar binding site to αVβ3 integrin. The anti-proliferative activity of endostatin was retained by all peptides except ES, and the in vitro anti-angiogenic property was preserved in ES-Zn and ES-SS. Remarkably, breast tumor growth and CD31 activity were inhibited more effectively by ES-SS than by ES-Zn. Therefore, a correlation exists between the N-terminal loop and anti-cancer properties of endostatin fragment and a disulfide loop may be more promising than a Zn binding loop for inhibiting tumor growth. © 2015 Elsevier Inc..

Related Docs

View other Related Docs

1. The Antiangiogenic and Antitumor Activities of the N-Terminal Fragment of Endostatin Augmented by Ile/Arg Substitution: The Overall Structure Implicated the Biological Activity, Biochimica et Biophysica Acta - Proteins and Proteomics (2016)

2. Effects of Exercise Training Together With Tamoxifen in Reducing Mammary Tumor Burden in Mice: Possible Underlying Pathway of Mir-21, European Journal of Pharmacology (2015)

3. Microrna-206, Let-7A and Microrna-21 Pathways Involved in the Anti-Angiogenesis Effects of the Interval Exercise Training and Hormone Therapy in Breast Cancer, Life Sciences (2016)

4. Encapsulation of Curcumin in Diblock Copolymer Micelles for Cancer Therapy, BioMed Research International (2015)

5. Glance Into Cancer Stem Cells, Journal of Kerman University of Medical Sciences (2016)

6. Tumor Suppression Effects of Myoepithelial Cells on Mice Breast Cancer, European Journal of Pharmacology (2015)

7. Therapeutic Effects of Dendrosomal Solanine on a Metastatic Breast Tumor, Life Sciences (2016)

8. Assessment of Cell Growth Inhibitory Effects of Myoepithelial Cells on Breast Carcinoma Cell Line, Journal of Zanjan University of Medical Sciences and Health Services (2016)

Experts (# of related papers)

View all Related Experts

Alimohammad Alizadeh (10)

Saeid Amanpour (1)

Style	Citing Format
MLA	Chamani R, et al.. "Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights." Vascular Pharmacology, vol. 72, no. , 2015, pp. 73-82.
APA	Chamani R, Asghari SM, Alizadeh AM, Eskandari S, Mansouri K, Khodarahmi R, Taghdir M, Heidari Z, Gorji A, Aliakbar A, Ranjbar B, Khajeh K (2015). Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights. Vascular Pharmacology, 72(), 73-82.
Chicago	Chamani R, Asghari SM, Alizadeh AM, Eskandari S, Mansouri K, Khodarahmi R, Taghdir M, et al.. "Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights." Vascular Pharmacology 72, no. (2015): 73-82.
Harvard	Chamani R et al. (2015) 'Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights', Vascular Pharmacology, 72(), pp. 73-82.
Vancouver	Chamani R, Asghari SM, Alizadeh AM, Eskandari S, Mansouri K, Khodarahmi R, et al.. Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights. Vascular Pharmacology. 2015;72():73-82.
BibTex	@article{ author = {Chamani R and Asghari SM and Alizadeh AM and Eskandari S and Mansouri K and Khodarahmi R and Taghdir M and Heidari Z and Gorji A and Aliakbar A and Ranjbar B and Khajeh K}, title = {Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights}, journal = {Vascular Pharmacology}, volume = {72}, number = {}, pages = {73-82}, year = {2015} }
RIS	TY - JOUR AU - Chamani R AU - Asghari SM AU - Alizadeh AM AU - Eskandari S AU - Mansouri K AU - Khodarahmi R AU - Taghdir M AU - Heidari Z AU - Gorji A AU - Aliakbar A AU - Ranjbar B AU - Khajeh K TI - Engineering of a Disulfide Loop Instead of a Zn Binding Loop Restores the Anti-Proliferative, Anti-Angiogenic and Anti-Tumor Activities of the N-Terminal Fragment of Endostatin: Mechanistic and Therapeutic Insights JO - Vascular Pharmacology VL - 72 IS - SP - 73 EP - 82 PY - 2015 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract