Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1α via the mTOR/p70S6K/4E-BP1 and MAPK pathways

Mi, Chunliu; Ma, Juan; Wang, Ke Si; Zuo, Hong Xiang; Wang, Zhe; Li, Ming Yue; Piao, Lian Xun; Xu, Guang; Li, Xuezheng; Quan, Zhe‐Shan; Jin, Xuejun

doi:10.1016/j.jep.2017.03.033

Cited by 98 publications

(58 citation statements)

References 35 publications

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“…The pharmacological properties of IMP make it a promising candidate for drug development. It has been documented to possess antioxidant [66,67], anti-inflammatory [68,69], anticancer [68,70], antibacterial [71], and antiallergic activities [72]. Singh et al reported that IMP treatment significantly reduced the 2…”

Section: Imperatorin (Imp)mentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

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The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.

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Section: Imperatorin (Imp)mentioning

confidence: 99%

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Hassanein

Sayed

Hussein

et al. 2020

Oxidative Medicine and Cellular Longevity

164

106

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“…Imperatorin is an active natural furocoumarin ingredient from Angelica dahurica. Mi et al (2017) reported that imperatorin administration could inhibit tumor growth and tumor angiogenesis in vivo and in vitro and downregulate HIF-1α activation by targeting the mTOR/p70S6K/4E-BP1 and MAPK pathways. 5,3'-Dihydroxy-6,7,4'-trimethoxyflavanone (DHTMF) is one of the main ingredients of Vitex rotundifolia.…”

Section: Inhibitors Of Signal Transduction Pathwaysmentioning

confidence: 99%

Dual Effects of Chinese Herbal Medicines on Angiogenesis in Cancer and Ischemic Stroke Treatments: Role of HIF-1 Network

et al. 2019

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Hypoxia-inducible factor-1 (HIF-1)-induced angiogenesis has been involved in numerous pathological conditions, and it may be harmful or beneficial depending on the types of diseases. Exploration on angiogenesis has sparked hopes in providing novel therapeutic approaches on multiple diseases with high mortality rates, such as cancer and ischemic stroke. The HIF-1 pathway is considered to be a major regulator of angiogenesis. HIF-1 seems to be involved in the vascular formation process by synergistic correlations with other proangiogenic factors in cancer and cerebrovascular disease. The regulation of HIF-1-dependent angiogenesis is related to the modulation of HIF-1 bioactivity by regulating HIF-1α transcription or protein translation, HIF-1α DNA binding, HIF-1α and HIF-1α dimerization, and HIF-1 degradation. Traditional Chinese herbal medicines have a long history of clinical use in both cancer and stroke treatments in Asia. Growing evidence has demonstrated potential proangiogenic benefits of Chinese herbal medicines in ischemic stroke, whereas tumor angiogenesis could be inhibited by the active components in Chinese herbal medicines. The objective of this review is to provide comprehensive insight on the effects of Chinese herbal medicines on angiogenesis by regulating HIF-1 pathways in both cancer and ischemic stroke.

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“…These patients cannot derive sufficient benefit even after receiving intensified adjuvant chemotherapy . Therefore, seeking more effective anti‐angiogenic agents would renew our enthusiasm for this therapeutic strategy …”

Section: Introductionmentioning

confidence: 99%

“…9 Therefore, seeking more effective anti-angiogenic agents would renew our enthusiasm for this therapeutic strategy. 10 Our previous work shows that intrinsic apoptosis is a feasible and efficacious pathway to eliminate transformed cells with damaged DNA and aberrant expression of oncogene. Arenobufagin isolated from skin and parotid venom glands (Chan'Su) is an active component that suppresses the progression of CRC by inducing intrinsic apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia‐inducible factor 1α axis

Chen

Dai

et al. 2019

Cancer Science

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Inducing angiogenesis is a hallmark of cancers that sustains tumor growth and metastasis. Neovascularization is a surprisingly early event during the multistage progression of cancer. Cinobufagin, an important bufadienolide originating from Chan Su, has been clinically used to treat cancer in China since the Tang dynasty. Here, we show that cinobufagin suppresses colorectal cancer ( CRC ) growth in vivo by downregulating angiogenesis. The hierarchized neovasculature is significantly decreased and the vascular network formation is disrupted in HUVEC by cinobufagin in a dose‐dependent way. Endothelial apoptosis is observed by inducing reactive oxygen species ( ROS ) accumulation and mitochondrial dysfunction which can be neutralized by N‐acetyl‐ l ‐cysteine ( NAC ). Expression of hypoxia‐inducible factor 1α ( HIF ‐1α) is reduced and phosphorylation of mTOR at Ser2481 and Akt at Ser473 is downregulated in HUVEC . Endothelial apoptosis is triggered by cinobufagin by stimulation of Bax and cascade activation of caspase 9 and caspase 3. Increased endothelial apoptosis rate and alterations in the HIF ‐1α/ mTOR pathway are recapitulated in tumor‐bearing mice in vivo. Further, the anti‐angiogenesis function of cinobufagin is consolidated based on its pro‐apoptotic effects on an EOMA ‐derived hemangioendothelioma model. In conclusion, cinobufagin suppresses tumor neovascularization by disrupting the endothelial mTOR / HIF ‐1α pathway to trigger ROS ‐mediated vascular endothelial cell apoptosis. Cinobufagin is a promising natural anti‐angiogenetic drug that has clinical translation potential and practical application value.

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Imperatorin suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1α via the mTOR/p70S6K/4E-BP1 and MAPK pathways

Cited by 98 publications

References 35 publications

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway

Dual Effects of Chinese Herbal Medicines on Angiogenesis in Cancer and Ischemic Stroke Treatments: Role of HIF-1 Network

Cinobufagin suppresses colorectal cancer angiogenesis by disrupting the endothelial mammalian target of rapamycin/hypoxia‐inducible factor 1α axis

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