Coptisine suppresses tumor growth and progression by down-regulating MFG-E8 in colorectal cancer

Cao, Qianyu; Hong, Shengwei; Li, Yuanyuan; Chen, Heng; Shen, Yining; Shao, Kang; Lu, Mengjie; Dai, Hui; Ma, Shengming; Dai, Guoliang

doi:10.1039/c8ra05806g

Cited by 21 publications

(12 citation statements)

References 22 publications

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“…For example, Han et al [ 19 ] demonstrated that coptisine induced apoptotic cell death through reactive oxygen species (ROS) production, a decline of mitochondrial membrane potential (MMP, ΔΨm), and activation of mitochondrial-associated apoptosis in human colon cancer. More current reports have suggested that coptisine inhibited cell growth, migration, and invasion via regulation of the phosphoinositide 3-kinases (PI3K)/Akt pathway in colorectal and pancreatic cancers [ 23 , 24 ]. Although several studies have shown that coptisine had anticancer activity against HCC, the underlying mechanism was unclear.…”

Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Kim

Hwangbo

Lee

et al. 2020

IJMS

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Hepatocellular carcinoma (HCC) has a high mortality rate worldwide, and treatment is very limited due to its high recurrence and low diagnosis rate, and therefore there is an increasing need to develop more effective drugs to treat HCC. Coptisine is one of the isoquinoline alkaloids, and it has various pharmacological effects. However, the evidence for the molecular mechanism of the anticancer efficacy is still insufficient. Therefore, this study investigated the antiproliferative effect of coptisine on human HCC Hep3B cells and identified the action mechanism. Our results showed that coptisine markedly increased DNA damage and apoptotic cell death, which was associated with induction of death receptor proteins. Coptisine also significantly upregulated expression of proapoptotic Bax protein, downregulated expression of anti-apoptotic Bcl-2 protein, and activated caspase-3, -8, and -9. In addition, coptisine remarkably increased the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (MMP), and release of cytochrome c into the cytoplasm. However, N-acetylcysteine (NAC), a ROS scavenger, significantly attenuated the apoptosis-inducing effect of coptisine. It is worth noting that coptisine significantly upregulated phosphorylation of ROS-dependent c-Jun N-terminal kinase (JNK), whereas treatment with JNK inhibitor could suppress an apoptosis-related series event. Taken together, our results suggest that coptisine has an anticancer effect in Hep3B cells through ROS-mediated activation of the JNK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Kim

Hwangbo

Lee

et al. 2020

IJMS

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“…Several studies have established that coptisine exerts ameliorative effect on cancer in in vivo model. Cao et al reported that coptisine (30‐90 mg/kg, i.p, once daily for 14 days) could prevent tumour development by inhibiting MFG‐E8, MMP‐2/9, N‐cadherin, vimentin and Snail expressions and increase E‐cadherin expression in HCT116‐challenged nude mouse . Interestingly, in the same xenograft tumour model, administration of coptisine (50‐150 mg/kg, oral, once daily for 25d) decreased serum level of tumour markers such as CEA, CA119 and CYFRA, and this effect was related to the changed mRNA expressions of TNF‐β, KRAS, ERK and p53 .…”

Section: Anti‐cancer Propertymentioning

confidence: 98%

“…Coptisine (0–25 μmol/L, 24 hours) was demonstrated to inhibit the viability, adhesion and migration of HCT116 cells and the expressions of MMP‐3 and MMP‐9. It also down‐regulated PI3K and Akt expression as well as altered the downstream EMT markers such as E‐cadherin, N‐cadherin, vimentin and Snail . Apoptosis plays a vital role in the progression of multiple cancers and basically activated by a mitochondria‐induced intrinsic or a death receptor‐induced extrinsic pathway, both of which are correlated with mitochondria and Bcl‐2 family anti‐apoptotic proteins .…”

Section: Anti‐cancer Propertymentioning

confidence: 99%

“…and Akt expression as well as altered the downstream EMT markers such as E-cadherin, N-cadherin, vimentin and Snail. 25 Apoptosis plays a vital role in the progression of multiple cancers and basically activated by a mitochondria-induced intrinsic or a death receptorinduced extrinsic pathway, both of which are correlated with mitochondria and Bcl-2 family anti-apoptotic proteins. [26][27][28] Another two studies on HCT-116 cells investigated the underlying mechanism of F I G U R E 2 Non-liner relationships between CC alkaloid dosages and plasma concentration (Cmax).…”

Section: Anti -C An Cer Propert Ymentioning

confidence: 99%

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Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

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Coptisine is a natural small‐molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as ‘coptisine’ in combination of ‘each pivotal pathway target’. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti‐cancer, anti‐inflammatory, CAD ameliorating or anti‐bacterial drug through regulating the signalling transduction of pathways such as NF‐κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non‐liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase‐1‐involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano‐ or microrods strategies or applying salt‐forming process to coptisine, can it be introduced to clinical trial.

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“…However, work on coptisine chloride also focused on the medicinal activities, such as the antitumor, anti-inflammatory, anti-hypercholesterolemic activity, and the distribution in rat. [31][32][33][34][35] To date, no herbicidal activity has been reported on worenine chloride and coptisine chloride.…”

Section: Summary Of Herbicidal Activitymentioning

confidence: 99%

Laboratory bioassay, greenhouse experiment and 3D‐QSAR studies on berberine analogues: a search for new herbicides based on natural products

Zhang

Zhu

et al. 2021

Pest Management Science

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BACKGROUND Berberine is a herbicidal chemical that we isolated from Coptis chinensis. In continuation of our program aimed at discovering and developing natural botanical herbicides, we evaluated the herbicidal activities of 39 berberine analogues and developed a three‐dimensional quantitative structure–activity relationship (3D‐QSAR) model. RESULTS Among these 39 analogs, the most active compounds were determined to be worenine chloride and coptisine chloride, with median inhibitory concentration (IC50) values on all eight tested weed species of < 10 mg L−1. As a reference, the IC50 values of berberine on six weed species were < 10 mg L−1. Furthermore, the results of a greenhouse experiment showed that at 10 mg L−1, and 7 days after treatment, the effects of worenine chloride and coptisine chloride on Lemna minor and Ageratum conyzoides were significantly higher than those of glyphosate and sulcotrione. In the 3D‐QSAR analysis, the electrostatic field contour map indicated that introducing an electropositive group in the N‐7, C‐9 and C‐10 positions would potentially improve the inhibition rate. A positively charged nitrogen atom at the N‐7 position was important for activity. Replacement of ‐OCH3 by ‐OH at the C‐9 and C‐10 positions could decrease the inhibitory activity, while the hydrophobic field contour map revealed that the hydrophobicity of the C‐10 position was associated with high activity. Moreover, the hydrogen bond acceptor field contour map suggested that the existence of a hydrogen bond acceptor at the C‐3 and C‐9 positions might affect the inhibition rate. CONCLUSIONS 3D‐QSAR provided meaningful clues to the structural features of berberine analogues that will assist the design of more potent herbicidal compounds in the future. © 2020 Society of Chemical Industry

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Coptisine suppresses tumor growth and progression by down-regulating MFG-E8 in colorectal cancer

Abstract: Treating colorectal cancer (CRC) continues to be a clinical challenge. Coptisine, an alkaloid derived from Coptis chinensis Franch. shows toxic effects on CRC cells, but its underlying mechanism remains elusive.

Cited by 21 publications

References 22 publications

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Induction of Apoptosis by Coptisine in Hep3B Hepatocellular Carcinoma Cells through Activation of the ROS-Mediated JNK Signaling Pathway

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Laboratory bioassay, greenhouse experiment and 3D‐QSAR studies on berberine analogues: a search for new herbicides based on natural products

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