Dihydromyricetin Enhances the Chemo-Sensitivity of Nedaplatin via Regulation of the p53/Bcl-2 Pathway in Hepatocellular Carcinoma Cells

Jiang, Liling; Zhang, Qingyu; Ren, Hao; Ma, Shenglin; Lu, Caijie; Liu, Bin; Liu, Jie; Liang, Jian; Li, Mingyi; Zhu, Runzhi

doi:10.1371/journal.pone.0124994

Cited by 37 publications

(35 citation statements)

References 20 publications

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“…TUG1 may be an important factor in the p53-regulatory network; p53 is a tumor suppressor gene, the mutation of which is associated with the occurrence and progression of numerous cancer types, including those of the liver (26), breast (27), bladder (28) and stomach (29). As reported, p53 may also serve an important function in the occurrence and development of brain glioma (30).…”

Section: Discussionmentioning

confidence: 87%

Downregulation of the long non-coding RNA taurine-upregulated gene 1 inhibits glioma cell proliferation and invasion and promotes apoptosis

et al. 2018

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Abstract. Expression of the long non-coding RNA taurine-upregulated gene 1 (TUG1) is associated with various aggressive tumors. The present study aimed to investigate the biological function of TUG1 in regulating apoptosis, proliferation, invasion and cell cycle distribution in human glioma U251 cells. Lentivirus-mediated TUG1-specific microRNA was transfected into U251 cells to abrogate the expression of TUG1. Flow cytometry analysis was used to examine the cell cycle distribution and apoptosis of U251 cells. Cellular proliferation was examined using Cell Counting Kit-8 (CCK-8) assays and invasion was examined by Transwell assays. The apoptotic rate of cells in the TUG1-knockdown group was significantly higher than in the negative control (NC) group (11.58 vs. 9.14%, P<0.01). CCK-8 assay data demonstrated that the proliferative ability of cells within the TUG1-knockdown group was lower compared with that of the NC group. A Transwell invasion assay was performed, which revealed that the number of invaded cells from the TUG1-knockdown group was the less compared with that of the NC group. In addition, the G 0 /G 1 phase population was significantly increased within the treated group (44.85 vs. 38.45%, P<0.01), as measured by flow cytometry. The present study demonstrated that the downregulation of TUG1 may inhibit proliferation and invasion, and promote glioma U251 cell apoptosis. In addition, knockdown of TUG1 may have an effect on cell cycle arrest.The data presented in the current study indicated that TUG1 may be a novel therapeutic target for glioma.

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Section: Discussionmentioning

confidence: 87%

Downregulation of the long non-coding RNA taurine-upregulated gene 1 inhibits glioma cell proliferation and invasion and promotes apoptosis

et al. 2018

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“…ROS produced by antitumor drugs is an important mechanism to induce tumor cell death due to hepatocyte toxicity, especially in steatotic livers 145. Repeated use of 10 mg/mL nedaplatin causes significant apoptosis by reducing Bcl-2 expression, enhancing p53 expression, and increasing ROS production and mitochondria damage in cultured normal hepatic cell lines 146. Interestingly, when the antioxidant dihydromyricetin was administered together with nedaplatin, normal hepatocytes were protected from DILI, and the effect of nedaplatin on tumor cells was enhanced 146…”

Section: Hepatocyte Apoptosis and Drug-induced Liver Injury (Dili)mentioning

confidence: 99%

Mechanism of Hepatocyte Apoptosis

et al. 2016

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Hepatocyte apoptosis plays important roles in both the removal of external microorganisms and the occurrence and development of liver diseases. Different conditions, such as virus infection, fatty liver disease, hepatic ischemia reperfusion, and drug-induced liver injury, are accompanied by hepatocyte apoptosis. This review summarizes recent research on the mechanism of hepatocyte apoptosis involving the classical extrinsic and intrinsic apoptotic pathways, endoplasmic reticulum stress, and oxidative stress-induced apoptosis. We emphasized the major causes of apoptosis according to the characteristics of different liver diseases. Several concerns regarding future research and clinical application are also raised.

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“…Suppression of thep53 pathway can reduce cell apoptosis and mitochondrial damage by the Bcl2 pathway [40]. …”

Section: Discussionmentioning

confidence: 99%

Downregulation of PRAME Suppresses Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma Through the Activation of P53 Mediated Pathway

Zhu

Wang

Yin

et al. 2018

Cell Physiol Biochem

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Background/Aims: The expression of PRAME and its role in hepatocellular carcinoma (HCC) remain unknown. The aim of this study was to examine the functional role of PRAME in HCC development and exploring the molecular mechanism. Methods: We first detected PRAME expression in 96 human HCC tissue samples and correlated with clinicopathological characteristics and prognosis of the patients. We then established stable HCC cell lines with PRAME overexpression and knockdown followed by functional analysis in vitro. Further, we examined the relationship between PRAME and p53 pathway in vitro by using Western blotting. Finally, PRAME expression was detected to evaluate its correlation with p-p53 and p53 pathway related apoptotic proteins in xenograft tumor mouse model using immunohistochemistry. Results: PRAME expression was significantly higher in HCC tissues than in adjacent non-tumor tissues and their expression was positively correlated with alpha fetoprotein levels and tumor size. In addition, PRAME expression was associated with AJCC stage and is a potential biomarker of poor prognosis regarding 5-year overall survival in HCC. In vitro studies, we found that PRAME expression was higher in HCC cell lines than in normal hepatic cell line. Inhibited cell proliferation and increased cell apoptosis was observed in PRAME knockdown HCC cells. Futher, increased cell apoptosis was correlated with the proportion of cells in G0/G1 stage, activated p53 mediated apoptosis, and increased cyclin p21 expression. Xenograft analysis in nude mice also found that PRAME knockdown inhibited tumorigenesis while PRAME overexpression had opposite effect. Conclusions: In HCC, PRAME serves as a potential biomarker for poor prognosis and novel therapeutic target in treating this cancer. PRAME is a potential biomarker of poor prognosis in HCC. PRAME surpresses HCC cell death in vitro and in vivo by regulating p53 apoptotic signaling and may serve as a potential therapeutic target in HCC.

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Dihydromyricetin Enhances the Chemo-Sensitivity of Nedaplatin via Regulation of the p53/Bcl-2 Pathway in Hepatocellular Carcinoma Cells

Cited by 37 publications

References 20 publications

Downregulation of the long non-coding RNA taurine-upregulated gene 1 inhibits glioma cell proliferation and invasion and promotes apoptosis

Downregulation of the long non-coding RNA taurine-upregulated gene 1 inhibits glioma cell proliferation and invasion and promotes apoptosis

Mechanism of Hepatocyte Apoptosis

Downregulation of PRAME Suppresses Proliferation and Promotes Apoptosis in Hepatocellular Carcinoma Through the Activation of P53 Mediated Pathway

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