Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

Bae, Moon‐Kyoung; Kim, Sehee; Jeong, Joo‐Won; Lee, You Mie; Kim, Hae-Sun; Kim, Su-Ryun; Yun, Il Dong; Bae, Soo-Kyung; Kim, Kyu‐Won

doi:10.3892/or.15.6.1557

Cited by 106 publications

(111 citation statements)

References 25 publications

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“…Recently, curcumin has been reported to inhibit HIF-1. 13,14 However, it is not clear how it exerts its anti-HIF activity. One group showed that curcumin affects only the HIF-1β (ARNT) subunit, 14 while another reported that curcumin inhibited HIF-1α.…”

Section: Resultsmentioning

confidence: 99%

“…One group showed that curcumin affects only the HIF-1β (ARNT) subunit, 14 while another reported that curcumin inhibited HIF-1α. 13 We treated PC3 human prostate cancer ( Fig. 2A) and MDA-MB-231 breast cancer cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…13,14 However, EF24 is not only significantly more active than curcumin, but it also inhibits HIF-1 via a totally distinct mechanism. We found that curcumin inhibited HIF-1α transcription only at the highest concentration examined (50-100 μM), whereas EF24 downregulated HIF-1α in a dose-dependent manner at low, sublethal concentrations.…”

Section: Introductionmentioning

confidence: 99%

“…12 In this study, we set out to elucidate aspects of the molecular mechanism of action of EF24. We focused on the reported antiangiogenic activities of curcumin, partially mediated by inhibition of the hypoxia-inducible factor (HIF-1) pathway 13,14 and determined whether EF24 had an effect on the HIF pathway.…”

Section: Introductionmentioning

confidence: 99%

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EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1

Thomas

Zhong²,

Zhou³

et al. 2008

Cell Cycle

109

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Curcumin, the yellow pigment of the spice turmeric, has emerged as a promising anticancer agent due to its antiproliferative and antiangiogenic properties. However, the molecular mechanism of action of this compound remains a subject of debate. In addition, curcumin's low bioavailability and efficacy profile in vivo further hinders its clinical development. This study focuses on the mechanism of action of EF24, a novel curcumin analog with greater than curcumin biological activity and bioavailability, but no increased toxicity. Treatment of MDA-MB231 breast and PC3 prostate cancer cells with EF24 or curcumin led to inhibition of HIF-1α protein levels and, consequently, inhibition of HIF transcriptional activity. This drug-induced HIF inhibition occurred in a VHL-dependent but proteasome-independent manner. We found that, while curcumin inhibited HIF-1α gene transcription, EF24 exerted its activity by inhibiting HIF-1α posttranscriptionally. This result suggested that the two compounds are structurally similar but mechanistically distinct. Another cellular effect that further differentiated the two compounds was the ability of EF24, but not curcumin, to induce microtubule stabilization in cells. EF24 had no stabilizing effect on tubulin polymerization in an in vitro assay using purified bovine brain tubulin, suggesting that the EF24-induced cytoskeletal disruption in cells may be the result of upstream signaling events rather than EF24 direct binding to tubulin. In summary, our study identifies EF24 as a novel curcumin-related compound possessing a distinct mechanism of action, which we believe contributes to the potent anticancer activity of this agent and can be further exploited to investigate the therapeutic potential of EF24.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1

Thomas

Zhong²,

Zhou³

et al. 2008

Cell Cycle

109

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show abstract

“…Another polyphenol antioxidant curcumin, a major yellow pigment found in turmeric and derived from the root of the plant Curcuma longa Linn, has been used for centuries in indigenous medicine for the treatment of a variety of inflammatory conditions and other diseases. There is some support for the therapeutic effect of curcumin in liver disease, as it was shown to block hypoxia-stimulated angiogenesis in vitro and downregulate HIF-1a and VEGF expression in vascular endothelial cells (Bae et al, 2006). Curcumin inhibits DEN-mediated increased expression of oncogenic p21/ WAF1, p53, PCNA, cyclin E and p34 proteins and attenuates NF-kB activation in liver of rats .…”

Section: Steroidsmentioning

confidence: 99%

NF-κB signaling, liver disease and hepatoprotective agents

2008

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Novel synthetic curcumin analogs as potent antiangiogenic agents in colorectal cancer

et al. 2016

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The transcription factor NF-kB plays a central role in angiogenesis in colorectal cancer (CRC). Curcumin is a natural dietary product that inhibits NF-kB. The objective of this study is to evaluate the antiangiogenic effects of curcumin and two potent synthetic analogues (EF31 and UBS109) in CRC. IC 50 values for curcumin, EF31, and UBS109 were determined in the HCT116 and HT-29 cell lines. HUVEC tube formation, egg CAM assay, and matrigel plug assays revealed decreased angiogenesis in cell lines treated with curcumin, EF31, or UBS109. Curcumin and its analogues significantly inhibited VEGF-A synthesis and secretion in both cell lines in association with loss of HIF-1a, COX-2, and p-STAT-3 expression. Nuclear NF-kB expression was inhibited by curcumin, EF31, and UBS109. Transfection of p65-NF-kB in HCT116 and HT-29 cells resulted in increased expression of HIF-1a, COX-2, STAT-3, and VEGF-A. Treatment with curcumin, EF31, or UBS109 inhibited these effects in transfected cell lines. In mice carrying HCT116 and HT-29 cell xenografts, EF31 and UBS109 inhibited subcutaneous tumor growth and potentiated the effects of oxaliplatin and 5-FU. Tumors from treated animals revealed inhibition of HIF-1a, COX-2, p-STAT-3, and VEGF expression. Our findings suggest that inhibition of NF-kB leading to decreased transcription and expression of HIF-1a, COX-2, STAT-3, and VEGF is a rational approach for antiangiogenic therapy in CRC. The distinctive properties of EF31 and UBS109 make them promising therapeutic agents for development in CRC as single agents or as part of combination chemotherapy regimens.

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Curcumin inhibits hypoxia-induced angiogenesis via down-regulation of HIF-1

Cited by 106 publications

References 25 publications

EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1

EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF-1

NF-κB signaling, liver disease and hepatoprotective agents

Novel synthetic curcumin analogs as potent antiangiogenic agents in colorectal cancer

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