Dataset Information

Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.

ABSTRACT: Natural products are a rich resource for the discovery of therapeutic substances. By directly using 504 fine fractions from isolated traditional Chinese medicine plants, we performed a transgenic zebrafish based screen for anti-angiogenesis substances. One fraction, DYVE-D3, was found to inhibit the growth of intersegmental vessels in the zebrafish vasculature. Bioassay-guided isolation of DYVE-D3 indicates that the flavonoid kaempferol was the active substance. Kaempferol also inhibited the proliferation and migration of HUVECs in vitro. Furthermore, we found that kaempferol suppressed angiogenesis through inhibiting VEGFR2 expression, which can be enhanced by FGF inhibition. In summary, this study shows that the construction of fine fraction libraries allows efficient identification of active substances from natural products.

SUBMITTER: Liang F

PROVIDER: S-EPMC4597183 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.

Liang Fang F Han Yuxiang Y Gao Hao H Xin Shengchang S Chen Shaodan S Wang Nan N Qin Wei W Zhong Hanbing H Lin Shuo S Yao Xinsheng X Li Song S

Scientific reports 20151008

Natural products are a rich resource for the discovery of therapeutic substances. By directly using 504 fine fractions from isolated traditional Chinese medicine plants, we performed a transgenic zebrafish based screen for anti-angiogenesis substances. One fraction, DYVE-D3, was found to inhibit the growth of intersegmental vessels in the zebrafish vasculature. Bioassay-guided isolation of DYVE-D3 indicates that the flavonoid kaempferol was the active substance. Kaempferol also inhibited the pro ...[more]

PMID: 26446489

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Project description:Non?small cell lung cancer (NSCLC) accounts for over 80% of all diagnosed lung cancer cases. Lung cancer is the leading cause of cancer?related deaths worldwide. Most NSCLC cells overexpress vascular endothelial growth factor?A (VEGF?A) which plays a pivotal role in tumour angiogenesis. Anti?angiogenic therapies including VEGF?A neutralisation have significantly improved the response rates, progression?free survival and overall survival of patients with NSCLC. However, the median survival of these patients is shorter than 18 months, suggesting that NSCLC cells secrete VEGF?independent angiogenic factors, which remain unknown. We aimed to explore these factors in human NSCLC cell lines, A549, Lu99 and EBC?1 using serum?free culture, to which only EBC?1 cells could adapt. By mass spectrometry, we identified 1,007 proteins in the culture supernatant derived from EBC?1 cells. Among the identified proteins, interleukin?8 (IL?8), macrophage migration inhibitory factor (MIF), galectin?1, midkine (MK), IL?18, galectin?3, VEGF?A, hepatoma?derived growth factor (HDGF), osteopontin (OPN), connective tissue growth factor (CTGF) and granulin (GRN) are known to be involved in angiogenesis. Tube formation, neutralisation and RNA interference assays revealed that VEGF?A and HDGF function as angiogenic factors in EBC?1 cells. To confirm whether VEGF?A and HDGF also regulate angiogenesis in the other NSCLC cell lines, we established a novel culture method. NSCLC cells were embedded in collagen gel and cultured three?dimensionally. Tube formation, neutralisation and RNA interference assays using the three?dimensional (3D) culture supernatant showed that VEGF?A and HDGF were not angiogenic factors in Lu99 cells. By gene microarray in EBC?1 and Lu99 cells, we identified 61 mRNAs expressed only in Lu99 cells. Among these mRNAs, brain?derived neurotrophic factor (BDNF), fibroblast growth factor?2 (FGF?2) and FGF?5 are known to be involved in angiogenesis. Tube formation and neutralisation assays clarified that FGF?2 functions as an angiogenic factor in Lu99 cells. These results indicate that HDGF enhances VEGF?dependent angiogenesis and that FGF?2 is a VEGF?independent angiogenic factor in human NSCLC cells.

Dataset Information

Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.

Publications

Kaempferol Identified by Zebrafish Assay and Fine Fractionations Strategy from Dysosma versipellis Inhibits Angiogenesis through VEGF and FGF Pathways.

Similar Datasets

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