Anti-Angiogenic Peptides for Cancer Therapeutics

Roşca, Elena; Koskimaki, Jacob E.; Rivera, Corban G.; Pandey, Niranjan B.; Tamiz, Amir P.; Popel, Aleksander S.

doi:10.2174/138920111796117300

Cited by 141 publications

(123 citation statements)

References 120 publications

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“…It has been systemically implicated in tumor therapy by reducing the number of newly-formed blood vessels (Rosca et al, 2011). Results from these clinical studies have proven the safety of this drug.…”

Section: Discussionmentioning

confidence: 99%

Endostatin inhibits hypertrophic scarring in a rabbit ear model

Ren

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Objective: The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation. Methods: Eight male New Zealand white rabbits were randomly assigned to two groups. Scar model was established by making six full skin defect wounds in each ear. For the intervention group, intraperitoneal injection of endostatin was performed each day after the wound healed (about 15 d post wounding). For the control group, equal volume of saline was injected. Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15, 21, 28, and 35 post wounding. Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding. Results: Macroscopically, scars of the control group were thicker than those of the intervention group. Significant differences between the two groups were observed on Days 21 and 35 (p<0.05). Scar thickness, measured by scar elevation index (SEI) at Day 35 post wounding, was significantly reduced in the intervention group (1.09±0.19) compared with the controls (1.36±0.28). Microvessel density (MVD) observed in the intervention group (1.73±0.94) was significantly lower than that of the control group (5.63±1.78) on Day 35. The distribution of collagen fibers in scars treated with endostatin was relatively regular, while collagen fibers in untreated controls were thicker and showed disordered alignment. Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin. Conclusions: Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation, possibly through reducing scar vascularization and angiogenesis. Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF), thereby controlling collagen production by fibroblasts. Blood vessel-targeted treatment may be a promising strategy for scar therapy.

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Section: Discussionmentioning

confidence: 99%

Endostatin inhibits hypertrophic scarring in a rabbit ear model

Ren

et al. 2013

J. Zhejiang Univ. Sci. B

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“…These suggest that modest but sustained increases in angiogenic inhibitors (angiostatin or endostatin) may be capable of significantly inhibiting tumor growth. Peptides have emerged as important therapeutics that is rigorously tested in angiogenesis-dependent diseases due to their low toxicity and high specificity (36). Since the discovery of endogenous proteins and protein fragments that inhibit microvessel formation (thrombospondin and endostatin), several peptides (including endostatin mimics and gelatinase inhibitory peptide CTTHWGFTLC) have shown promise in preclinical and clinical studies for cancer (23,37).…”

Section: Discussionmentioning

confidence: 99%

“…Since the discovery of endogenous proteins and protein fragments that inhibit microvessel formation (thrombospondin and endostatin), several peptides (including endostatin mimics and gelatinase inhibitory peptide CTTHWGFTLC) have shown promise in preclinical and clinical studies for cancer (23,37). Angiogenesis inhibitors, particularly polypeptides or endogenous peptides, may become the safest and least toxic therapy for diseases associated with abnormal angiogenesis (36,37). However, the use of peptides in vivo has largely been limited by their extremely short half-life.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide–Endostatin Mimic–Kringle 5 Protein

Wang

Yang

2014

Molecular Cancer Therapeutics

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Angiogenesis is required for tumor growth and metastasis, and targeting angiogenesis is a novel anticancer strategy. However, cancer development is a complex multistep process, and single antiangiogenic agents have limited therapeutic efficacy. Here, we report a triple fusion protein, namely CTT peptideendostatin mimic-kringle 5 (AARP), consisting of MMP-2/9-selective inhibitory peptide (CTT peptide) and well-known endogenous antiangiogenic agents (endostatin mimic and kringle 5), which can simultaneously target matrix metalloproteinases (MMP) and endothelial cells, blocking their actions. AARP was bacterially expressed, and biologic activity of purified AARP was assessed. AARP could significantly inhibit the enzymatic activity of MMP-2/9, proliferation, migration, and tube formation of endothelial cells in vitro. The antitumor activity of AARP was shown in a concentration-dependent manner when injected i.p. into immunodeficient mice bearing multidrug-resistant human epidermoid carcinomas (KB), and AARP is superior to clinical grade endostatin in inhibiting KB xenograft growth. In mouse models of Lewis lung carcinoma (LLC) and hepatoma H22, when given as a single dose, AARP is highly effective for reducing tumor growth, angiogenesis, and metastasis, and increasing survival time. AARP possessed significantly greater antiangiogenic activity than endostatin mimic, CTT peptide-kringle 5 (RK5) both in vitro and in vivo. Compared with conventional chemotherapeutic agents (cyclophosphamide and paclitaxel), AARP is also effective. More importantly, AARP is cytocompatible and no tissue toxicity could be observed after large dose administration. Taken together, our findings suggest AARP is a highly effective, safe, and more potent antiangiogenic agent for blocking tumor angiogenesis and metastasis, and warrants further testing for clinical applications.

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“…Peptides can be used as drugs, hormones, or immunization agents (vaccines) (Sah et al 2015). The biological effects include inhibition of tumor vasculature growth (angiogenesis), alterations in protein-protein interaction, changes in gene expression, and apoptosis, among others (Rosca et al 2011;Walensky et al 2004;Zheng et al 2011).…”

Section: Peptide-based Strategies For Cancermentioning

confidence: 99%

Anticancer Peptides: Prospective Innovation in Cancer Therapy

Gaspar

Castanho

2016

Host Defense Peptides and Their Potential as Therapeutic Agents

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Current cancer treatments require improvements in selectivity and efficacy. Surgery, radiation, and chemotherapy approaches result in patient's suffering over time due to the development of severe side-effects that simultaneously condition adherence to therapy. Biologically active peptides, in particular antimicrobial peptides (AMPs), are versatile molecules in terms of biological activities. The cytotoxic activities of several AMPs turn this group of molecules into an amazing pool of new templates for anticancer drug development. However, several unmet challenges limit application of peptides in cancer therapy. The mechanism(s) of action of the peptides need better description and understanding, and innovative targets have to be discovered and explored, facilitating drug design and development. In this chapter, we explore the natural occurring AMPs as potential new anticancer peptides (ACPs) for cancer prevention and treatment. Their modes of action, selectivity to tumor compared to normal cells, preferential targets, and applications, but also their weaknesses, are described and discussed.

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Anti-Angiogenic Peptides for Cancer Therapeutics

Cited by 141 publications

References 120 publications

Endostatin inhibits hypertrophic scarring in a rabbit ear model

Endostatin inhibits hypertrophic scarring in a rabbit ear model

Therapeutic Targeting of Angiogenesis with a Recombinant CTT Peptide–Endostatin Mimic–Kringle 5 Protein

Anticancer Peptides: Prospective Innovation in Cancer Therapy

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