Dihydroartemisinin induces apoptosis preferentially via a Bim-mediated intrinsic pathway in hepatocarcinoma cells

This report is designed to dissect the detail molecular mechanism by which dihydroartemisinin (DHA), a derivative of artemisinin, induces apoptosis in human hepatocellular carcinoma (HCC) cells. DHA induced a loss of the mitochondrial transmemberane potential (ΔΨm), release of cytochrome c, activation of caspases, and externalization of phosphatidylserine indicative of apoptosis induction. Compared with the modest inhibitory effects of silencing Bax, silencing Bak largely prevented DHA-induced ΔΨm collapse and apoptosis though DHA induced a commensurable activation of Bax and Bak, demonstrating a key role of the Bak-mediated intrinsic apoptosis pathway. DHA did not induce Bid cleavage and translocation from cytoplasm to mitochondria and had little effects on the expressions of Puma and Noxa, but did increase Bim and Bak expressions and decrease Mcl-1 expression. Furthermore, the cytotoxicity of DHA was remarkably reduced by silencing Bim, and modestly but significantly reduced by silencing Puma or Noxa. Silencing Bim or Noxa preferentially reduced DHA-induced Bak activation, while silencing Puma preferentially reduced DHA-induced Bax activation, demonstrating that Bim and to a lesser extent Noxa act as upstream mediators to trigger the Bak-mediated intrinsic apoptosis pathway. In addition, silencing Mcl-1 enhanced DHA-induced Bak activation and apoptosis. Taken together, our data demonstrate a crucial role of Bim in preferentially regulating the Bak/Mcl-1 ...
Source: Apoptosis - Category: Molecular Biology Source Type: research

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CONCLUSION: These results indicate that serum miR-19b-3p level is a crucial biomarker for ICC diagnosis and targeting miR-19b-3p-CCDC6 axis might be a promising strategy in ICC therapy. PMID: 32315652 [PubMed - as supplied by publisher]
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research
This study demonstrated that trillin could dramatically inhibit hepatoma carcinoma cell proliferation, induce apoptosis and decrease migration and invasion through suppressing phosphorylated STAT3 translocated to nucleus. Trillin could down-regulate Bcl-2 and Survivin, up-regulate cleaved PRAP, leading to dramatically apoptosis; trillin could also down-regulate MMP1, MMP2, MucI and VEGF, which displayed an inhibition effect on hepatocellular tumor cells invasion and development. The results of this study indicated the potential utility of trillin as a STAT3 inhibitor for the treatment of cancers.
Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
Authors: Jia M, Xiong Y, Li M, Mao Q Abstract Chemotherapy is critical for the treatment of hepatocellular carcinoma (HCC). Despite the pro-apoptotic effects of corosolic acid (CA) treatment, its underlying mechanism is not completely clear. The aim of this study was to determine the molecular mechanism of CA in HCC treatment. MTT assay was used to determine the IC50 of CA. Immunoprecipitation and immunofluorescence were used to detect the interaction between and subcellular localization of Yes-associated protein (YAP) and mouse double minute 2 (MDM2). In addition, in vivo xenotransplantation was performed to asses...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research
In conclusion, benzbromarone increases mitochondrial O2•- accumulation and activates the NRF2 signaling pathway in HepG2 cells, thereby strengthening the cytosolic and mitochondrial antioxidative defense. Impaired antioxidative defense may represent a risk factor for benzbromarone-induced hepatotoxicity. PMID: 32198009 [PubMed - as supplied by publisher]
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
In this study we explored the underlying mechanisms of PFOA and GenX induced hepatocellular damage. Liver hepatocellular carcinoma cell line HepG2 was used as a model to study induced liver inflammation in vitro at the cellular, genetic, and epigenetic levels. HepG2 cells were exposed to PFOA or GenX for 48 h and the DNA and RNA were extracted and analyzed. mRNA expression of PFOA exposed cells showed that the cell cycle genes were affected significantly, as well as the ten-eleven translocation methylcytosine dioxygenases (TETs) and the essential lipid metabolism genes. However, GenX did not have as significant an effect...
Source: Toxicology in Vitro - Category: Toxicology Authors: Tags: Toxicol In Vitro Source Type: research
Publication date: Available online 11 February 2020Source: Life SciencesAuthor(s): Shuang Zhao, Ke Xu, Rong Jiang, Dan-Yang Li, Xing-Xian Guo, Peng Zhou, Jia-Feng Tang, Li-Sha Li, Di Zeng, Ling Hu, Jian-Hua Ran, Jing Li, Di-Long ChenAbstractAimsDysfunction of the Hippo-Yes-Associated Protein (YAP) signaling pathway is known to be associated with hepatocellular carcinoma (HCC). Evodiamine (Evo), a plant-derived bioactive alkaloid, exerts inhibitory effects on cancer. However, the precise influence of Evo on HCC and its potential effects on Hippo-YAP signaling have yet to be ascertained. Here, the effects of Evo on cell prol...
Source: Life Sciences - Category: Biology Source Type: research
UBE2M promotes cell proliferation via the β-catenin/cyclin D1 signaling in hepatocellular carcinoma. Aging (Albany NY). 2020 Feb 03;12: Authors: Zhang GC, Yu XN, Sun JL, Xiong J, Yang YJ, Jiang XM, Zhu JM Abstract Upregulated ubiquitin-conjugating enzyme E2M (UBE2M) is associated with poor prognosis in malignancies; However, the phenotype and mechanism of action of UBE2M in hepatocellular carcinoma (HCC) remain elusive. Here, we report that UBE2M is overexpressed and correlated with poor prognosis in HCC patients. The UBE2M level is an independent prognostic factor for HCC patients. UBE2M knockdo...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
Cell Death &Disease, Published online: 16 January 2020; doi:10.1038/s41419-020-2225-6The nuclear translocation of transketolase inhibits the farnesoid receptor expression by promoting the binding of HDAC3 to FXR promoter in hepatocellular carcinoma cell lines
Source: Cell death and disease - Category: Internal Medicine Authors: Source Type: research
In this study, we revealed that the DLC-1-deficient, but not the DLC-1-competent, human non-small cell lung carcinoma cells (NSCLCs) could acquire the TGF-β1-induced expression of CD105, a common surface marker of mesenchymal stem cells, with consequent increase in CD105-associated cell motility. Interestingly, the induced CD105 expression and cell motility were subjected to the inhibition by the DLC-1-RhoA-Rock1 signaling through inhibiting the serine phosphorylation at a linker region, but not at the C-terminus, of the Smad3 protein and Smad3 protein nuclear translocation down the canonical TGF-β1 signaling. In...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
In conclusion, we demonstrate that S1R protects HCC cells against sorafenib and subsequent ferroptosis. A better understanding of the role of S1R in ferroptosis may provide novel insight into this biological process. PMID: 31507082 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
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