NDLI: A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo

Content Provider	PubMed Central
Author	Catalano, Stefania Leggio, Antonella Barone, Ines Marco, Rosaria De Gelsomino, Luca Campana, Antonella Rocco, Malivindi Panza, Salvatore Giordano, Cinzia Liguori, Alessia Daniela, Bonofiglio Liguori, Angelo Andò, Sebastiano
Copyright Year	2015
Abstract	The role of the obesity cytokine leptin in breast cancer progression has raised interest in interfering with leptin's actions as a valuable therapeutic strategy. Leptin interacts with its receptor through three different binding sites: I–III. Site I is crucial for the formation of an active leptin–leptin receptor complex and in its subsequent activation. Amino acids 39-42 (Leu-Asp-Phe-Ile- LDFI) were shown to contribute to leptin binding site I and their mutations in alanine resulted in muteins acting as typical antagonists. We synthesized a small peptide based on the wild-type sequence of leptin binding site I (LDFI) and evaluated its efficacy in antagonizing leptin actions in breast cancer using in vitro and in vivo experimental models. The peptide LDFI abolished the leptin-induced anchorage-dependent and -independent growth as well as the migration of ERα-positive (MCF-7) and -negative (SKBR3) breast cancer cells. These results were well correlated with a reduction in the phosphorylation levels of leptin downstream effectors, as JAK2/STAT3/AKT/MAPK. Importantly, the peptide LDFI reversed the leptin-mediated up-regulation of its gene expression, as an additional mechanism able to enhance the peptide antagonistic activity. The described effects were specific for leptin signalling, since the developed peptide was not able to antagonize the other growth factors' actions on signalling activation, proliferation and migration. Finally, we showed that the LDFI pegylated peptide markedly reduced breast tumour growth in xenograft models. The unmodified peptide LDFI acting as a full leptin antagonist could become an attractive option for breast cancer treatment, especially in obese women.
Related Links	http://dx.doi.org/10.1111/jcmm.12517
Ending Page	1132
Page Count	11
Starting Page	1122
File Format	PDF
ISSN	15821838
e-ISSN	15824934
Journal	Journal of Cellular and Molecular Medicine
Issue Number	5
Volume Number	19
Language	English
Publisher	BlackWell Publishing Ltd
Publisher Date	2015-05-01
Access Restriction	Open
Rights Holder	BlackWell Publishing Ltd
Subject Keyword	Molecular Medicine Cell Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo

BRCC2 inhibits breast cancer cell growth and metastasis in vitro and in vivo via downregulating AKT pathway

A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo

NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo

A novel bFGF antagonist peptide inhibits breast cancer cell growth.

Nef-M1, a CXCR4 Peptide Antagonist, Enhances Apoptosis and Inhibits Primary Tumor Growth and Metastasis in Breast Cancer

Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model

A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth.

A novel antiangiogenic peptide derived from hepatocyte growth factor inhibits neovascularization in vitro and in vivo

A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo

Similar Documents

A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo

BRCC2 inhibits breast cancer cell growth and metastasis in vitro and in vivo via downregulating AKT pathway

A Peptide Antagonist of the ErbB1 Receptor Inhibits Receptor Activation, Tumor Cell Growth and Migration In Vitro and Xenograft Tumor Growth In Vivo

NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo

A novel bFGF antagonist peptide inhibits breast cancer cell growth.

Nef-M1, a CXCR4 Peptide Antagonist, Enhances Apoptosis and Inhibits Primary Tumor Growth and Metastasis in Breast Cancer

Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model

A vasoactive intestinal peptide antagonist inhibits non-small cell lung cancer growth.

A novel antiangiogenic peptide derived from hepatocyte growth factor inhibits neovascularization in vitro and in vivo

A novel leptin antagonist peptide inhibits breast cancer growth in vitro and in vivo