Dataset Information

Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract.

ABSTRACT: Coptidis rhizoma (CR; Huanglian in Chinese) has been used for the treatment of cancer in Chinese medicine, and recent studies have supported its use in cancer therapy. MicroRNAs (miRNAs) play an important role in the pathophysiology of human cancers. We examined alterations in the miRNA profile of hepatocellular carcinoma (HCC) cells after treatment with Coptidis rhizoma aqueous extract (CRAE). An on-chip microarray method was used to detect alterations in the expression profile of miRNAs in human HCC MHCC97-L cells after exposure to 175 ?g/ml CRAE. Altered expression of several miRNAs was detected in the MHCC97-L cells after treatment with 175 ?g/ml CRAE. The microarray results were validated by quantitative real-time PCR (qRT-PCR). Consistent results were obtained; qRT-PCR confirmed that both miR-21 and miR-23a were significantly up-regulated. TargetScan and PicTar microRNA databases were used to predict the possible target genes of the altered miRNAs. The results showed that the altered miRNAs after CRAE treatment may serve as markers for the therapy of liver cancer. To the best of our knowledge, this is the first report on the up-regulation of miRNAs, miR21 and miR23a in human liver cancer cells treated with CRAE. Our results suggest that CRAE targets miR-21 and miR-23a in liver cancer cells supporting the potential application of CRAE in the treatment of HCC.

SUBMITTER: Zhu M

PROVIDER: S-EPMC3440660 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract.

Zhu Meifen M Wang Ning N Tsao Sai-Wah SW Yuen Man-Fung MF Feng Yigang Y Wan Thomas S K TS Man Kwan K Feng Yibin Y

Experimental and therapeutic medicine 20101119 1

Coptidis rhizoma (CR; Huanglian in Chinese) has been used for the treatment of cancer in Chinese medicine, and recent studies have supported its use in cancer therapy. MicroRNAs (miRNAs) play an important role in the pathophysiology of human cancers. We examined alterations in the miRNA profile of hepatocellular carcinoma (HCC) cells after treatment with Coptidis rhizoma aqueous extract (CRAE). An on-chip microarray method was used to detect alterations in the expression profile of miRNAs in hum ...[more]

PMID: 22977465

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Project description:The aim of this study was to evaluate the osteoprotective effect of aqueous Rhizoma Dioscoreae extract (RDE) on the alveolar bone of rats with ovariectomy-induced bone loss. Female Wistar rats underwent either ovariectomy or sham operation (SHAM). The ovariectomized (OVX) rats were treated with vehicle (OVX), estradiol valerate (EV), or RDE. After treatments, the bone mineral density (BMD) and the three-dimensional microarchitecture of the alveolar bone were analyzed to assess bone mass. Microarrays were used to evaluate microRNA expression profiles in alveolar bone from RDE-treated and OVX rats. The differential expression of microRNAs was validated using real-time quantitative RT-PCR (qRT-PCR), and the target genes of validated microRNAs were predicted and further analyzed using Ingenuity Pathway Analysis (IPA). The key findings were verified using qRT-PCR. Our results show that RDE inhibits alveolar bone loss in OVX rats. Compared to the OVX rats, the RDE-treated rats showed upregulated expression levels of 8 microRNAs and downregulated expression levels of 8 microRNAs in the alveolar bone in the microarray analysis. qRT-PCR helped validate 13 of 16 differentially expressed microRNAs, and 114 putative target genes of the validated microRNAs were retrieved. The IPA showed that these putative target genes had the potential to code for proteins that were involved in the transforming growth factor (TGF)-?/bone morphogenetic proteins (BMPs)/Smad signaling pathway (Tgfbr2/Bmpr2, Smad3/4/5, and Bcl-2) and interleukin (IL)-6/oncostatin M (OSM)/Jak1/STAT3 signaling pathway (Jak1, STAT3, and Il6r). These experiments revealed that RDE could inhibit ovariectomy-induced alveolar bone loss in rats. The mechanism of this anti-osteopenic effect in alveolar bone may involve the simultaneous inhibition of bone formation and bone resorption, which is associated with modulation of the TGF-?/BMPs/Smad and the IL-6/OSM/Jak1/STAT3 signaling pathways via microRNA regulation.

Project description:Primary plant metabolites can be used for artificial preparation of natural deep eutectic solvents (NADESs), which have strong dissolving capacity, good biocompatibility, and biodegradability. In this study, for the first time, we verified that NADESs were present in Coptidis Rhizoma extract and systematically investigated its effects and mechanisms on the pharmacokinetics of oral berberine hydrochloride (BBR), a co-existing bioactive constituent. First, three LC-MS/MS based methods were established and fully validated to determine the levels of 11 primary metabolites in Coptidis Rhizoma extract. According to the weight ratio of four major primary metabolites in the Coptidis Rhizoma extract, a stable "endogenous" NADES was prepared using the heating method by the addition of 350 μl of water to 1,307.8 mg of the mixture of malic acid (490.5 mg), glucose (280.6 mg), sucrose (517.7 mg), and choline chloride (19.0 mg). The prepared NADES showed significant acute toxicity in mice and cytotoxicity in MDCK-MDR1 cells. However, after being diluted 10 times or 100 times, the NADES had no significant acute toxicity or cytotoxicity, respectively. The dilutions of the NADES significantly increased the water solubility of BBR, reduced its efflux in gut sacs and MDCK-MDR1 cell monolayer, and improved its metabolic stability in intestinal S9. In addition, the NADES dilutions reversibly opened the tight junctions between the enterocytes in the gut sacs. Moreover, the NADES dilutions significantly improved the exposure levels of BBR in the portal vein and livers of mice that were administered oral BBR. Malic acid was identified as a major component in the NADES in terms of solubility, acute toxicity, cytotoxicity, and pharmacokinetic-improving effects on oral BBR. In conclusion, the primary metabolites of Coptidis Rhizoma extract could form "endogenous" NADES, and its dilutions improve the pharmacokinetics of oral BBR. This study demonstrates the synergistic interaction of the constituents of Coptidis Rhizoma extract and the potential use of the NADES dilutions in oral BBR delivery.

Dataset Information

Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract.

Publications

Up-regulation of microRNAs, miR21 and miR23a in human liver cancer cells treated with Coptidis rhizoma aqueous extract.

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