Kaempferol Inhibits Angiogenesis and VEGF Expression Through Both HIF Dependent and Independent Pathways in Human Ovarian Cancer Cells

Luo, Haitao; Rankin, Gary O.; Liu, Lingzhi; Daddysman, Matthew K.; Jiang, Bing-Hua; Chen, Yi Charlie

doi:10.1080/01635580802666281

Cited by 168 publications

(142 citation statements)

References 43 publications

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“…Regardless, these results suggest that antilymphatics may be best given in conjunction with other compounds that prevent tumor growth. Previous work has shown that kaempferol consumption has been associated with reduced risk of developing many cancers (38)(39)(40) and has also been shown to reduce VEGF expression in human cancer cell lines (41,42). To our knowledge, this study is the first to report VEGFR inhibition and antilymphatic activity for kaempferol.…”

Section: Discussionmentioning

confidence: 62%

An In Vivo Antilymphatic Screen in Zebrafish Identifies Novel Inhibitors of Mammalian Lymphangiogenesis and Lymphatic-Mediated Metastasis

Astin

Jamieson

Eng

et al. 2014

Molecular Cancer Therapeutics

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The growth of new lymphatic vessels (lymphangiogenesis) in tumors is an integral step in the metastatic spread of tumor cells, first to the sentinel lymph nodes that surround the tumor and then elsewhere in the body. Currently, no selective agents designed to prevent lymphatic vessel growth have been approved for clinical use, and there is an important potential clinical niche for antilymphangiogenic agents. Using a zebrafish phenotype-based chemical screen, we have identified drug compounds, previously approved for human use, that have antilymphatic activity. These include kaempferol, a natural product found in plants; leflunomide, an inhibitor of pyrimidine biosynthesis; and cinnarizine and flunarizine, members of the type IV class of calcium channel antagonists. Antilymphatic activity was confirmed in a murine in vivo lymphangiogenesis Matrigel plug assay, in which kaempferol, leflunomide, and flunarizine prevented lymphatic growth. We show that kaempferol is a novel inhibitor of VEGFR2/3 kinase activity and is able to reduce the density of tumorassociated lymphatic vessels as well as the incidence of lymph node metastases in a metastatic breast cancer xenograft model. However, in this model, kaempferol administration was also associated with tumor deposits in the pancreas and diaphragm, and flunarizine was found to be tumorigenic. Although this screen revealed that zebrafish is a viable platform for the identification and development of mammalian antilymphatic compounds, it also highlights the need for focused secondary screens to ensure appropriate efficacy of hits in a tumor context. Mol Cancer Ther; 13(10); 2450-62. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 62%

An In Vivo Antilymphatic Screen in Zebrafish Identifies Novel Inhibitors of Mammalian Lymphangiogenesis and Lymphatic-Mediated Metastasis

Astin

Jamieson

Eng

et al. 2014

Molecular Cancer Therapeutics

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“…Some researchers report that kaempferol is a chemical that is used as an anti-angiogenesis in ovarian cancer therapy (Luo et al 2009). These chemical compounds contained in plant Cayratia trifolia L (Domin) as a test to prove the progression of a cancer cell.…”

Section: Discussionmentioning

confidence: 99%

“…The chemicals contained by Cayratia trifolia is stilbenes (such as: piceid, resveratrol, viniferin, and ampelopsin), kaempferol, quercetin (Kumar et al 2011). Some researchers report that kaempferol is a chemical that is used as an anti-angiogenesis in ovarian cancer therapy (Luo et al 2009). In malignant cancer in the gland structures are organized as colorectal epithelium.…”

Section: Introductionmentioning

confidence: 99%

EFFECT OF Cayratia trifolia L (Domin) EXTRACT ON REDUCED EXPRESSION OF MATRIX METALLOPROTEINASE-9 (MMP–9) AND VASCULAR ENDOTHELIAL GROWTH FACTOR –A (VEGF-A) IN WHITE RATS WITH BREAST CANCER

Dewi¹,

Sudiana²

2017

FMI

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ABSTRAKAngka kejadian kanker payudara setiap tahun mengalami peningkatan, salah satu upaya untuk mengatasi kanker payudara adalah dengan terapi anti-angiogenesis yang berfungsi untuk menghambat pertumbuhan dan metastasis dari sel kanker, proses angiogenesis dan metastasis pada sel kanker sangat berhubungan dengan ekspresi ABSTRACT The number of cancer cases in every year has increased. One effort in reducing breast cancer cases is by using anti-angiogenesis which could prevent the growth and metastasis of cancer cells. Xxx the process of angiogenesis and metastasis in cancer cells are associated with the expression of Matrixmetalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor (VEGF). To reduce metastasis in cancer cells, it can be performed by giving plant extracts Cayratiatrifolia L (Domin), containing the active compound

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“…15 Kaempferol is also effective in inhibiting angiogenesis and inducing apoptosis in ovarian cancer cells. [16][17][18][19] In human studies, a significant 40% decrease in incidence of ovarian cancer was found for individuals with the highest quintile of kaempferol intake as compared with those in the lowest quintile. 20 Despite promising preclinical results, the utility of such compounds for chemoprevention in humans has met with only limited success, largely due to inefficient systemic delivery and limited bioavailability of promising agents.…”

Section: Introductionmentioning

confidence: 99%

“…31 Chemoprevention of ovarian cancer using natural products has received more attention recently, and our earlier studies have indicated that kaempferol, a dietary flavonoid, is effective in inhibiting angiogenesis and inducing apoptosis in ovarian cancer cells. [16][17][18][19] However, effective concentrations are often above 20-40 µM, which are not always physiologically attainable. In this study, five nanoparticle formulations of kaempferol were developed and their efficacy in inhibiting the viability of malignant and normal ovarian cells was determined.…”

Section: Introductionmentioning

confidence: 99%

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

Luo¹,

Jiang²,

Li³

et al. 2012

IJN

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Abstract:Ovarian cancer is one of the leading causes of cancer death for women throughout the Western world. Kaempferol, a natural flavonoid, has shown promise in the chemoprevention of ovarian cancer. A common concern about using dietary supplements for chemoprevention is their bioavailability. Nanoparticles have shown promise in increasing the bioavailability of some chemicals. Here we developed five different types of nanoparticles incorporating kaempferol and tested their efficacy in the inhibition of viability of cancerous and normal ovarian cells. We found that positively charged nanoparticle formulations did not lead to a significant reduction in cancer cell viability, whereas nonionic polymeric nanoparticles resulted in enhanced reduction of cancer cell viability. Among the nonionic polymeric nanoparticles, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) nanoparticles incorporating kaempferol led to significant reduction in cell viability of both cancerous and normal cells. Poly(DL-lactic acid-co-glycolic acid) (PLGA) nanoparticles incorporating kaempferol resulted in enhanced reduction of cancer cell viability together with no significant reduction in cell viability of normal cells compared with kaempferol alone. Therefore, both PEO-PPO-PEO and PLGA nanoparticle formulations were effective in reducing cancer cell viability, while PLGA nanoparticles incorporating kaempferol had selective toxicity against cancer cells and normal cells. A PLGA nanoparticle formulation could be advantageous in the prevention and treatment of ovarian cancers. On the other hand, PEO-PPO-PEO nanoparticles incorporating kaempferol were more effective inhibitors of cancer cells, but they also significantly reduced the viability of normal cells. PEO-PPO-PEO nanoparticles incorporating kaempferol may be suitable as a cancer-targeting strategy, which could limit the effects of the nanoparticles on normal cells while retaining their potency against cancer cells. We have identified two nanoparticle formulations incorporating kaempferol that may lead to breakthroughs in cancer treatment. Both PEO-PPO-PEO and PLGA nanoparticle formulations had superior effects compared with kaempferol alone in reducing cancer cell viability.

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Kaempferol Inhibits Angiogenesis and VEGF Expression Through Both HIF Dependent and Independent Pathways in Human Ovarian Cancer Cells

Cited by 168 publications

References 43 publications

An In Vivo Antilymphatic Screen in Zebrafish Identifies Novel Inhibitors of Mammalian Lymphangiogenesis and Lymphatic-Mediated Metastasis

An In Vivo Antilymphatic Screen in Zebrafish Identifies Novel Inhibitors of Mammalian Lymphangiogenesis and Lymphatic-Mediated Metastasis

EFFECT OF Cayratia trifolia L (Domin) EXTRACT ON REDUCED EXPRESSION OF MATRIX METALLOPROTEINASE-9 (MMP–9) AND VASCULAR ENDOTHELIAL GROWTH FACTOR –A (VEGF-A) IN WHITE RATS WITH BREAST CANCER

Kaempferol nanoparticles achieve strong and selective inhibition of ovarian cancer cell viability

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