Inhibitors of Angiogenesis in Cancer Therapy – Synthesis and Biological Activity

Gensicka, Monika; Głowacka, Agnieszka; Dzierzbicka, Krystyna; Cholewiński, Grzegorz

doi:10.2174/0929867322666150904111442

Cited by 10 publications

(7 citation statements)

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“…Tumor angiogenesis is an essential process for cancer progression, as angiogenic vessels supply nutrients and oxygen to the tumor [23, 24]. Vascular endothelial cells (ECs) in the angiogenic process move toward the tumor and form new vessels [25, 26].…”

Section: Introductionmentioning

confidence: 99%

SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2

et al. 2016

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Tumor angiogenesis is a key feature of cancer progression, because a tumor requires abundant oxygen and nutrition to grow. Here, we demonstrate that SH003, a mixed herbal extract containing Astragalus membranaceus (Am), Angelica gigas (Ag) and Trichosanthes Kirilowii Maximowicz (Tk), represses VEGF-induced tumor angiogenesis both in vitro and in vivo. SH003 inhibited VEGF-induced migration, invasion and tube formation in human umbilical vein endothelial cells (HUVEC) with no effect on the proliferation. SH003 reduced CD31-positive vessel numbers in tumor tissues and retarded tumor growth in our xenograft mouse tumor model, while SH003 did not affect pancreatic tumor cell viability. Consistently, SH003 inhibited VEGF-stimulated vascular permeability in ears and back skins. Moreover, SH003 inhibited VEGF-induced VEGFR2-dependent signaling by blocking VEGF binding to VEGFR2. Therefore, our data conclude that SH003 represses tumor angiogenesis by inhibiting VEGF-induced VEGFR2 activation, and suggest that SH003 may be useful for treating cancer.

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Section: Introductionmentioning

confidence: 99%

SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2

et al. 2016

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“…Angiogenesis plays a key role in tumor growth and metastasis [15], and it is a multi-step process requiring coordinated endothelial functions, such as the activation of endothelial cells, degradation of the basement membrane, migration and proliferation of endothelial cells, elongation and branching of vessels, acquisition of pericytes, and ECM remodeling [49]. VEGF is a key factor in angiogenesis, and it is highly expressed in a wide variety of human cancers [12].…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic Activity of Coptis chinensis Franch. Water Extract in in vitro and ex vivo Angiogenesis Models

Kim¹,

Kim²,

Lee³

et al. 2017

Journal of Life Science

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Angiogenesis, the formation of new blood vessels, plays an important role in tumor growth and metastasis; therefore, it has become an important target in cancer therapy. Novel anticancer pharmaceutical products that have relatively few side effects or are non-cytotoxic must be developed, and such products may be obtained from traditional herbal medicines. Coptis chinensis Franch. is an herb used in traditional medicine for the treatment of inflammatory diseases and diabetes. However, potential antiangiogenic effects of C. chinensis water extract (CCFWE) have not yet been studied. The purpose of this study was to determine the antiangiogenic effect of CCFWE in order to evaluate its potential for an anticancer drug. We found that the treatment with CCFWE inhibited the major steps of the angiogenesis process, such as the endothelial cell proliferation, migration, invasion, and capillary-like tube formation in response to vascular endothelial growth factor (VEGF), and also resulted in the growth inhibition of new blood vessels in an ex vivo rat aortic ring assay. We also observed that CCFWE treatment arrested the cell cycle at the G0/G1 phase, preventing the G0/G1 to S phase cell cycle progression in response to VEGF. In addition, the treatment reduced the VEGF-induced activation of matrix metalloproteinases 2 and 9. Taken together, these findings indicate that CCFWE should be considered a potential anticancer therapy against pathological conditions where angiogenesis is stimulated during tumor development.

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“…Inhibition of angiogenesis, by targeting VEGF-VEGFR signaling, has revolutionised cancer therapy with improved outcomes in some previously untreatable cancers. Four major classes of VEGFI are currently used clinically, including monoclonal VEGF antibodies (bevacizumab), monoclonal VEGFR antibodies (ramucirumab), soluble decoy receptors (VEGF traps) (aflibercept) and small molecule VEGFR tyrosine kinase inhibitors (TKI) (sunitinib, cabozantinib, pazopanib, axitinib, vandetanib, regorafenib) (8,9) (figure 2). Since endothelial cells are physiologically quiescent, no adverse effects during anti-angiogenesis therapy were expected.…”

Section: Vegf Signaling As a Target For Anti-angiogenic And Anti-cancmentioning

confidence: 99%

Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition

et al. 2017

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Physiologically, vascular endothelial growth factors (VEGF) and their receptors (VEGFR) play a critical role in vascular development, neogenesis, angiogenesis, endothelial function and vascular tone. Pathologically, VEGF-VEGFR signaling induces dysregulated angiogenesis, which contributes to the growth and spread of tumors. The development of VEGF-VEGFR inhibitors (VEGFIs) has thus proven to be a valuable strategy in the management of a number of malignancies, yielding improved survival outcomes. Not surprisingly, VEGFIs are now standard of care as first-line monotherapy for some cancers and the scope of this class of drugs is growing. However with the promise of improved outcomes, VEGFIs also led to clinically relevant toxicities, especially hypertension and cardiovascular disease (CVD). As such, cancer patients treated with VEGFIs may have improved cancer outcomes, but at the cost of an increased risk of CVD. Indeed, dose intensity and protracted use of these drugs can be limited by cardiovascular side effects and patients may require dose reduction or drug withdrawal, thus compromising anti-cancer efficacy and survival. Here we summarize the vascular biology of VEGF-VEGFR signaling and discuss the cardiovascular consequences and clinical impact of VEGFIs. New insights into molecular mechanisms whereby VEGFIs cause hypertension and heart disease are highlighted.

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Inhibitors of Angiogenesis in Cancer Therapy – Synthesis and Biological Activity

Cited by 10 publications

References 0 publications

SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2

SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2

Antiangiogenic Activity of Coptis chinensis Franch. Water Extract in in vitro and ex vivo Angiogenesis Models

Recent Advances in Hypertension and Cardiovascular Toxicities With Vascular Endothelial Growth Factor Inhibition

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