JIB‑04 induces cell apoptosis via activation of the p53/Bcl‑2/caspase pathway in MHCC97H and HepG2 cells

Liao, Weiguo; Liu, Jie; Liu, Bin; Huang, Xiaojie; Yin, Yuexin; Cai, De; Li, Mingyi; Zhu, Runzhi

doi:10.3892/or.2018.6737

Cited by 8 publications

(10 citation statements)

References 39 publications

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“…The upregulation of TP53 expression that is induced by rAd-p53 treatment promoted human cervical cancer cell apoptosis through activation of the Bax gene and suppression of the Bcl-x gene and resulted in cell cycle arrest at the G 2 /M phase ( 40 ). The results of the present study are consistent with those observed in previous reports, which have demonstrated that TP53 activation is associated with liver cancer cell apoptosis by regulating the expression of Bcl-2 and caspases ( 41 , 42 ), in addition to inhibiting cancer cell migration ( 43-45 ). TP53 activation has also been previously reported to serve an inhibitory role in the EMT process, in human oral mucosal fibroblasts and oral submucous fibrosis by downregulating N-cadherin expression ( 46 ) and in colorectal cancer cells by downregulating Snail expression ( 37 ), which are findings consistent with the results of the present study.…”

Section: Discussionsupporting

confidence: 93%

“…EMT was also notably suppressed, as demonstrated by the downregulation of N-cadherin, snail and twist expression, which are well documented markers of EMT (37,38). (41,42), in addition to inhibiting cancer cell migration (43)(44)(45). TP53 activation has also been previously reported to serve an inhibitory role in the EMT process, in human oral mucosal fibroblasts and oral submucous fibrosis by downregulating N-cadherin expression (46) and in colorectal cancer cells by downregulating Snail expression (37), which are findings consistent with the results of the present study.…”

Section: Discussionsupporting

confidence: 92%

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Combined effect of recombinant human adenovirus p53 and curcumin in the treatment of liver cancer

Chen

et al. 2020

Exp Ther Med

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The development of an effective therapeutic intervention for liver cancer is a worldwide challenge that remains to be adequately addressed. Of note, TP53, which encodes the p53 protein, is an important tumor suppressor gene, 61% of TP53 is functionally inactivated in liver cancer. Recombinant human adenovirus p53 (rAd-p53) is the first commercial product that has been used for gene therapy. In the present study, the combined mechanistic effects of rAd-p53 and curcumin, a naturally occurring compound with previously reported anti-inflammatory, antioxidant and anti-cancer properties, were assessed in liver cancer cells, using HepG2 cells as the model cell line. The administration of either curcumin or rAd-p53 promoted apoptosis, suppressed epithelial-mesenchymal transition (EMT) and blocked G2/M phase progression in HepG2 cells, which were potentiated further when both agents were applied together. Combined rAd-p53 and curcumin treatment resulted in higher p53 (P<0.01) and p21 (P<0.01) expression compared with rAd-p53 or curcumin were added alone, suggesting an additive effect on TP53 expression. Additionally, curcumin and rAd-p53 were demonstrated to regulate the activation of mitogen-activated protein kinases (MAPKs) ERK1/2, p38 MAPK and JNK. These results indicated that the combination of rAd-p53 with curcumin synergistically potentiates apoptosis and inhibit EMT compared with either rAd-p53 or curcumin treatment alone via the regulation of TP53 regulation. Mechanistically, this effect on TP53 expression may involve the ERK1/2, p38 MAPK and JNK signaling pathways. The current study provides new insights that can potentially advance the development of therapeutic strategies for liver cancer treatment.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 92%

Combined effect of recombinant human adenovirus p53 and curcumin in the treatment of liver cancer

Chen

et al. 2020

Exp Ther Med

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“…Tumor protein p53 induces cell cycle arrest and apoptosis through the transcriptional regulation of BAX gene. The protein also upregulates Bak expression, and the activation of Bax and Bak induces activation of caspase-3 [31]. In HepG2 cells, we have found that R2-viniferin tended to arrest cell cycle at G2/M phase, increased intracellular ROS levels, and the Bax/Bcl2 ratio in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 79%

Screening of Natural Stilbene Oligomers from Vitis vinifera for Anticancer Activity on Human Hepatocellular Carcinoma Cells

et al. 2020

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The characterization of bioactive resveratrol oligomers extracted from Vitis vinifera canes has been recently reported. Here, we screened six of these compounds (ampelopsin A, trans-ε-viniferin, hopeaphenol, isohopeaphenol, R2-viniferin, and R-viniferin) for their cytotoxic activity to human hepatocellular carcinoma (HCC) cell lines p53 wild-type HepG2 and p53-null Hep3B. The cytotoxic efficacy depended on the cell line. R2-viniferin was the most toxic stilbene in HepG2, with inhibitory concentration 50 (IC50) of 9.7 ± 0.4 µM at 72 h, 3-fold lower than for resveratrol, while Hep3B was less sensitive (IC50 of 47.8 ± 2.8 µM). By contrast, hopeaphenol (IC50 of 13.1 ± 4.1 µM) and isohopeaphenol (IC50 of 26.0 ± 3.0 µM) were more toxic to Hep3B. Due to these results, and because it did not exert a large cytotoxicity in HH4 non-transformed hepatocytes, R2-viniferin was selected to investigate its mechanism of action in HepG2. The stilbene tended to arrest cell cycle at G2/M, and it also increased intracellular reactive oxygen species (ROS), caspase 3 activity, and the ratio of Bax/Bcl-2 proteins, indicative of apoptosis. The distinctive toxicity of R2-viniferin on HepG2 encourages research into the underlying mechanism to develop the oligostilbene as a therapeutic agent against HCC with a particular genetic background.

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“…It has been previously reported that TNBS-induced colitis is associated with apoptosis of the colonic epithelial cells and its toxicology is thought to be related to the induction of apoptosis and the destruction of the intestinal mucosal barrier [24,25]. In IBD, there are high levels of apoptosis in the intestinal epithelium of patients [26,27]. The increased number of apoptotic epithelial cells and elevated Bax but attenuated Bcl-2 during active colitis may lead to a defective epithelial barrier and result in pathogenic microorganism in ltration.…”

Section: Anemoside B4 Suppressed Tnbs-induced Proliferation and Apoptmentioning

confidence: 99%

Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway

Zhang¹,

Zha²,

Shen³

et al. 2020

Preprint

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Background: Despite the increased morbidity of ulcerative colitis (UC) in the developing countries, available treatments remain unsatisfactory. Therefore, it is urgent to discover more effective therapeutic strategies. Pulsatilla chinensis was widely used for the treatment of inflamed intestinal diseases including UC for thousands of years in China. Anemoside B4, the most abundant triterpenoid saponin isolated from P. chinensis, exerts anti-inflammatory and antioxidant effects and may be the most active compounds, which is responsible for the therapeutic effects. However, the mechanism how anemoside B4 executes its biological functions is still elusive.Methods: Here, we used the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model to evaluate the therapeutic effect of anemoside B4. Blood samples of colitis rats were collected for hematology analysis. The inflammation-associated factors were investigated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis was determined with EdU cell proliferation assay and TUNEL assay. The proteins regulated by anemoside B4 were identified by label-free quantitative proteomics. The significantly down-regulated proteins were verified by Western blotting analysis. mRNA expression was analyzed by quantitative real-time RT-PCR.Results: The results showed that anemoside B4 ameliorated TNBS-induced colitis symptoms, including tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine production, apoptosis and slowed proliferation in colon. Quantitative proteomic analyses discovered that 56 proteins were significantly altered by anemoside B4 in the TNBS-induced rats. These proteins mainly clustered in tricarboxylic acid (TCA) cycle and respiratory electron transport chain. Among the altered proteins, S100A9 is one of the most significantly down-regulated proteins and associated with NF-κB and MAPK signaling pathways in the pathogenesis of UC. Further experiments revealed that anemoside B4 suppressed the expression of S100A9 and its downstream genes including TLR4 and NF-κB in colon. In vitro, anemoside B4 could inhibit the NF-κB signaling pathway induced by recombinant S100A9 protein in human intestinal epithelial Caco-2 cells. Moreover, anemoside B4 inhibits neutrophils recruitment and activation in colon induced by TNBS.Conclusions: Our results demonstrate that anemoside B4 prevents TNBS-induced colitis by inhibiting the NF-κB signaling pathway through deactivating S100A9, suggesting that anemoside B4 is a promising therapeutic candidate for colitis.

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JIB‑04 induces cell apoptosis via activation of the p53/Bcl‑2/caspase pathway in MHCC97H and HepG2 cells

Cited by 8 publications

References 39 publications

Combined effect of recombinant human adenovirus p53 and curcumin in the treatment of liver cancer

Combined effect of recombinant human adenovirus p53 and curcumin in the treatment of liver cancer

Screening of Natural Stilbene Oligomers from Vitis vinifera for Anticancer Activity on Human Hepatocellular Carcinoma Cells

Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway

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