A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

Zhao, Jian; Sang, Meixiang; Chen, Geng; Wang, Shijie; Shan, Baoen

doi:10.3892/ol.2016.5126

Cited by 17 publications

(17 citation statements)

References 50 publications

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“…Many in vitro and in vivo studies describe curcumin as a promising anticancer drug [ 15 , 16 , 17 , 18 ], but its instability and poor metabolic properties limit its clinical application [ 19 ]. Therefore, curcumin analogues are frequently investigated for improved chemical properties that still maintain its anticancer activity [ 21 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

Lima

Seba

Silva

et al. 2018

IJMS

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Curcumin is a potential anticancer drug with poor bioavailability, which limits its clinical use as a therapeutic agent. The aim of this study was a preliminary evaluation of the curcumin analogue CH-5 as a cytotoxic agent in human osteosarcoma cell lines U2OS, MG-63, and Saos-2. CH-5 inhibited cell viability at lower concentrations than curcumin, leading to the induction of apoptosis. The cellular levels of the transcription factors p53 and Sp1 affect the expression of cellular pathways that lead to apoptosis. CH-5 increased p53 protein levels in U2OS cells and reduced Sp1 levels, with a consequent effect on the expression of their target genes DNA methyltransferase 1 (DNMT1) and growth arrest and DNA damage-inducible 45 alpha gene (Gadd45a). CH-5 repressed DNMT1 and increased Gadd45a mRNA expression, which was dependent on p53, as this effect was only observed in the colorectal cancer cell line HCT116 with active p53, but not in the isogenic p53-deficient HCT116 cells. CH-5 also reduced the protein levels of DNMT1, which led to the upregulation of Gadd45a. These results suggest that CH-5 has potentially higher anticancer activity than curcumin, which is associated with the expression of apoptosis-associated genes regulated by the transcription factors Sp1 and p53. Future work on CH-5 will define the therapeutic potential of this compound in vivo.

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Section: Discussionmentioning

confidence: 99%

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

Lima

Seba

Silva

et al. 2018

IJMS

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“…Hepatocellular carcinoma (HCC) is the 5 th most common malignant tumor with ~600,000 new diagnosis leading to >250,000 mortalities annually 1 . Surgical resection and liver transplantation are currently most common medical procedures for non-metastatic liver cancers.…”

Section: Introductionmentioning

confidence: 99%

Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress.

Mehmood¹,

Maryam²,

Tian³

et al. 2017

J. Cancer

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Sesquiterpene lactones have long been used in traditional Chinese medicines to treat inflammatory diseases. Recently, sesquiterpene lactone family compounds have been recognized as potential anticancer agents. Thus, it is necessary to explore new sesquiterpene lactones and their antitumor mechanism for cancer treatments. In the present study, we have explored the potential anti-cancer activity of a novel sesquiterpene lactone compound “santamarine” (STM) in HepG2 cells. It inhibited proliferation and induced apoptosis dose-dependently with IC50 ~ 70 μM. Induction of apoptosis was found to be linked with increased reactive oxygen species (ROS) generation, decreased activity of thioredoxin reductase (TrxR), glutathione (GSH) depletion, mitochondrial membrane potential (ΔΨm) dissipation, Bcl-2 family proteins modulation, cytochrome c release, caspases-9, -8 and -3 activation and PARP cleavage. Further mechanistic study demonstrated that STM inhibited the constitutive and TNF-α-induced translocation of NF-кB into nucleus by decreasing phosphorylation of IkB-α. Moreover, STM inhibited STAT3 activation by decreasing phosphorylation at tyrosine705. NAC pretreatment reversed the effect of STM-mediated cell death, NF-кB inhibition and blockage of STAT3 activity, indicating the involvement of oxidative stress in STM-mediated anticancer activity. Further studies are needed to explore the exact molecular mechanism of STM-induced apoptosis to develop it into a lead for treatment of liver cancer in future.

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“…Hepatocellular carcinoma (HCC) is a common malignancy worldwide, with ~600,000 newly diagnosed cases, and leading to > 250,000 mortalities annually 1 , 20 . DEN is a potent hepatocarcinogenic nitrosamine that could induce lesion as well as tumors in rodents with marked biochemical, histological and molecular similarity to the progression of HCC in humans 21 , 22 .…”

Section: Discussionmentioning

confidence: 99%

Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid

Zhang

Wang

Qiao

et al. 2017

Sci Rep

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Hepatocellular carcinoma (HCC) treatment remains lack of effective chemopreventive agents, therefore it is very attractive and urgent to discover novel anti-HCC drugs. In the present study, the effects of chlorogenic acid (ChA) and caffeic acid (CaA) on HCC induced by diethylnitrosamine (DEN) were evaluated. ChA or CaA could reduce the histopathological changes and liver injury markers, such as alanine transarninase, aspartate aminotransferase, alkaline phosphatase, total bile acid, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol. The underlying mechanisms were investigated by a data integration strategy based on correlation analyses of metabonomics data and 16 S rRNA gene sequencing data. ChA or CaA could inhibit the increase of Rumincoccaceae UCG-004 and reduction of Lachnospiraceae incertae sedis, and Prevotella 9 in HCC rats. The principal component analysis and partial least squares discriminant analysis were applied to reveal the metabolic differences among these groups. 28 different metabolites showed a trend to return to normal in both CaA and ChA treatment. Among them, Bilirubin, L-Tyrosine, L-Methionine and Ethanolamine were correlated increased Rumincoccaceae UCG-004 and decreased of Lachnospiraceae incertae sedis and Prevotella 9. These correlations could be identified as metabolic and microbial signatures of HCC onset and potential therapeutic targets.

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A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma

Cited by 17 publications

References 50 publications

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

The Curcumin Analog CH-5 Exerts Anticancer Effects in Human Osteosarcoma Cells via Modulation of Transcription Factors p53/Sp1

Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress.

Metabolic and microbial signatures in rat hepatocellular carcinoma treated with caffeic acid and chlorogenic acid

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