SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

Zhang, Huiming; He, Shikun; Spee, Christine; Ishikawa, Keijiro; Hinton, David R.

doi:10.1016/j.cyto.2015.06.019

Cited by 45 publications

(40 citation statements)

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“…Notably, VEGFR2 plays a key role in the VEGF/VEGFR2 pathway in regards to angiogenesis and tumor growth [24, 25]. Recent researches show that VEGF regulates VEGFR2 by forming directly physical interaction with VEGFR2 [23, 26–31] and/or induces the phosphorylation of VEGFR2 [27–32]. There are many studies related to downstream targets of VEGFR2, such as the PI3K/Akt pathway [33].…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way

Xie

Liu

et al. 2016

BMC Cancer

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BackgroundThe study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers.MethodsInhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins.ResultsBoth tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin.ConclusionsTanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2921-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way

Xie

Liu

et al. 2016

BMC Cancer

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“…Retinal pigment epithelial cells express and secrete VEGF, which is the main source of VEGF in the retina . Loss of RPE cells causes atrophy of choriocapillaris ,.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of RPE cells causes atrophy of choriocapillaris ,. Hypoxia stimulated the expression and secretion of VEGF by RPE cells via the accumulation of HIF‐1α protein in the cells …”

Section: Discussionmentioning

confidence: 99%

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Hypoxia‐induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia‐inducible factors‐1α protein

Lai

Rosen

et al. 2016

Clinical Exper Ophthalmology

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“…In a work developed by Igura et al [149], resveratrol was shown to inhibit proliferation, migration and tube formation in BAECs, although the exact molecular mechanism of action was not studied. Zhang et al [150] verified that resveratrol significantly inhibited HIF-1a and VEGF expression, under hypoxia conditions. Another study performed by Cullberg et al [151] also verified the ability of resveratrol to inhibit key factors in hypoxia conditions in human adipose tissue, specifically it was observed that resveratrol inhibited VEGF expression.…”

Section: Antiangiogenic Potential Of Phenolic Compoundsmentioning

confidence: 99%

Antiangiogenic compounds: well-established drugs versus emerging natural molecules

et al. 2018

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a b s t r a c tAngiogenesis is the natural and physiologic process of growing blood vessels from pre-existing ones. Pathological angiogenesis occurs when the precise balance of all the molecular pathways that regulate angiogenesis is disrupted, and this process is a critical step in many diseases, including cancer. A limited number of antiangiogenic synthetic drugs have been developed. However, due to toxicity and side effects issues, the search for alternative to existing drugs is ongoing. In this sense, natural molecules obtained from plants or macrofungi, have demonstrated extraordinary potential in the treatment of angiogenesisrelated pathologies, specially taking into consideration its absence or very low toxicity, when compared to synthetic drugs. Using natural compounds as potential angiogenesis modulators is thus a promising field of research, supporting the creation of novel therapies able to reduce the use of drugs and associated side effects. In this review, the current status of antiangiogenic drugs and the wide variety of natural extracts and molecules with antiangiogenic capacities, as well as the angiogenesis molecular pathways and therapeutic targets, are presented. Finally, the challenges that need to be overcome in order to increase the use of natural compounds for clinical purposes are discussed.

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SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

Cited by 45 publications

References 11 publications

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way

Hypoxia‐induced vascular endothelial growth factor secretion by retinal pigment epithelial cells is inhibited by melatonin via decreased accumulation of hypoxia‐inducible factors‐1α protein

Antiangiogenic compounds: well-established drugs versus emerging natural molecules

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