scholarly journals Apoptin Mediates Endogenous Mitophagy and Apoptosis by Regulating the Level of ROS in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Yiquan Li ◽  
Chao Shang ◽  
Zirui Liu ◽  
Jicheng Han ◽  
Wenjie Li ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Tumor Model ◽  
Activation Mechanism ◽  
Mouse Tumor ◽  
Liver Cancer Cells ◽  
Key Factor

Abstract Background: Apoptin, as a tumor-specific pro-apoptotic protein, apoptin plays an important role in the field of anti-tumor, but its autophagy activation mechanism and the interaction between autophagy and apoptosis have not been accurately elucidated. Here, we studied the mechanism of apoptosis and autophagy induced by apoptin and the interaction between autophagy and apoptosis. Methods: Through crystal violet staining and CCK-8 assay, we analyzed the effect of apoptin in inhibiting liver cancer in vitro, and also analyzed the effect of inhibiting liver cancer in vivo by establishing a nude mouse tumor model. Flow cytometry and fluorescence staining were used to analyze the main types of apoptosis and autophagy induced by apoptin. Subsequently, the relationship between apoptosis and autophagy induced by apoptin was analyzed. Then, flow cytometry was used to analyze the effect of ROS on apoptosis and autophagy mediated by apoptin. Then, the affect of ROS on apoptosis and autophagy mediated by apoptin was analyzed. Finally, the key genes leading to autophagy were analyzed by silencing different genes.Results: The results showed that apoptin can significantly increase the apoptosis and autophagy of liver cancer cells, and apoptin can cause mitophagy through the increase of NIX protein. Apoptin can also significantly reduce the level of cellular ROS, which is related to the autophagy and apoptosis of liver cancer cells caused by apoptin. The change of ROS may be a key factor causing apoptosis and autophagy. Conclusion: The above results indicate that the increase of ROS level after apoptin treatment of liver cancer cells leads to the loss of mitochondrial transmembrane potential, which leads to endogenous apoptosis and mitophagy while recruiting NIX. Therefore, ROS may be a key factor connecting endogenous apoptosis and mitophagy induced by apoptin in liver cancer cells.

scholarly journals Azaindole inhibits liver cancer cell proliferation in vitro and in vivo by targeting the expression of kinesin family member C1

2022 ◽  
Vol 20 (2) ◽  
pp. 359-364
Author(s):  
Zhen You ◽  
Bei Li ◽  
Jun Gao ◽  
Jiong Lu ◽  
Ruihua Xu
Keyword(s):  
Cell Proliferation ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Tumor Development ◽  
Subcutaneous Administration ◽  
Tumor Model ◽  
Underlying Mechanism ◽  
Liver Cancer Cells

Purpose: To investigate the effect of azaindole on proliferation of liver cancer cells, as well as the underlying mechanism. Methods: Colony forming and 3-(4,5-dimethylthiazole-2-yl)-2,5-biphenyl tetrazolium bromide (MTT) assays were used to determine the effect of azaindole on cell proliferation. A tumor model was established through subcutaneous administration of HEPG2 cells to rats. Thereafter, in vivo tumor development was measured using Vernier caliper. Results: The proliferation potential of HEPG2 and SNU-398 cells was markedly and dose-dependently suppressed by treatment with azaindole at doses of 2, 4, 8, 16 and 20 μM (p < 0.05). The expression levels of Ki67 and PCNA levels were significantly down-regulated in HEPG2 and SNU-398 cells on treatment with 20 μM azaindole. Moreover, azaindole significantly suppressed mRNA and protein expressions of KIFC1 in HEPG2 and SNU-398 cells (p < 0.05). Tumor volume in azaindole-treated rats on day 21 was greatly reduced, while KIFC1 expression in azaindole-treated rat tumor tissue was significantly down-regulated, when compared to the model group (p < 0.05). Conclusion: Azaindole targets proliferation of liver cancer cells in vitro and inhibits tumor growth in vivo through a mechanism involving down-regulation of KIFCI expression. Thus, azaindole is a potential therapeutic candidate for liver cancer.

scholarly journals Synergistic Interaction between the HDAC Inhibitor, MPT0E028, and Sorafenib in Liver Cancer Cells In Vitro and In Vivo

2014 ◽  
Vol 20 (5) ◽  
pp. 1274-1287 ◽  
Author(s):  
Chun-Han Chen ◽  
Mei-Chuan Chen ◽  
Jing-Chi Wang ◽  
An-Chi Tsai ◽  
Ching-Shih Chen ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Hdac Inhibitor ◽  
Synergistic Interaction ◽  
Liver Cancer Cells

scholarly journals Low dose amiodarone reduces tumor growth and angiogenesis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eliana Steinberg ◽  
Arnon Fluksman ◽  
Chalom Zemmour ◽  
Katerina Tischenko ◽  
Adi Karsch-Bluman ◽  
...  
Keyword(s):  
Side Effects ◽  
Cancer Cells ◽  
Low Dose ◽  
Tumor Model ◽  
In Vitro Assays ◽  
Potential Candidate ◽  
Key Factor ◽  
Angiogenic Effect

Abstract Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug’s harmful side effects.

Growth inhibitory effects of pegylated IFN ?-2b on human liver cancer cells in vitro and in vivo

2006 ◽  
Vol 26 (8) ◽  
pp. 964-975 ◽  
Author(s):  
Hirohisa Yano ◽  
Sachiko Ogasawara ◽  
Seiya Momosaki ◽  
Jun Akiba ◽  
Sakiko Kojiro ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Inhibitory Effects ◽  
Liver Cancer Cells ◽  
Growth Inhibitory ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

The MAP30 protein from bitter gourd (Momordica charantia) seeds promotes apoptosis in liver cancer cells in vitro and in vivo

2012 ◽  
Vol 324 (1) ◽  
pp. 66-74 ◽  
Author(s):  
Evandro Fei Fang ◽  
Chris Zhi Yi Zhang ◽  
Jack Ho Wong ◽  
Jia Yun Shen ◽  
Chuan Hao Li ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Momordica Charantia ◽  
Bitter Gourd ◽  
Liver Cancer Cells

scholarly journals Composite fatty acid ether amides suppress growth of liver cancer cells in vitro and in an in vivo allograft mouse model

2013 ◽  
Vol 36 (3) ◽  
pp. 247-257 ◽  
Author(s):  
Mengde Cao ◽  
Victor Prima ◽  
David Nelson ◽  
Stanislav Svetlov
Keyword(s):  
Fatty Acid ◽  
Liver Cancer ◽  
Mouse Model ◽  
Cancer Cells ◽  
Liver Cancer Cells

Carbidopa is an activator of aryl hydrocarbon receptor with potential for cancer therapy

2017 ◽  
Vol 474 (20) ◽  
pp. 3391-3402 ◽  
Author(s):  
Jiro Ogura ◽  
Seiji Miyauchi ◽  
Kazumi Shimono ◽  
Shengping Yang ◽  
Sathisha Gonchigar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Liver Cancer ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Anticancer Effect ◽  
Liver Cancer Cells ◽  
Aryl Hydrocarbon

Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo. Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect. The inhibitory effect was confirmed using human recombinant IDO1. To demonstrate the inhibition in intact cells, AhR (aryl hydrocarbon receptor) activity was monitored as readout for IDO1-mediated generation of the endogenous AhR agonist kynurenine in pancreatic and liver cancer cells. Surprisingly, Carbidopa did not inhibit but instead potentiated AhR signaling, evident from increased CYP1A1 (cytochrome P450 family 1 subfamily A member 1), CYP1A2, and CYP1B1 expression. In pancreatic and liver cancer cells, Carbidopa promoted AhR nuclear localization. AhR antagonists blocked Carbidopa-dependent activation of AhR signaling. The inhibitory effect on pancreatic cancer cells in vitro and in vivo and the activation of AhR occurred at therapeutic concentrations of Carbidopa. Chromatin immunoprecipitation assay further confirmed that Carbidopa promoted AhR binding to its target gene CYP1A1 leading to its induction. We conclude that Carbidopa is an AhR agonist and suppresses pancreatic cancer. Hence, Carbidopa could potentially be re-purposed to treat pancreatic cancer and possibly other cancers as well.

scholarly journals Knockdown of lncRNA LINC01234 Suppresses The Tumorigenesis of Liver Cancer via Sponging miR-513a-5p

2020 ◽  
Author(s):  
Wen Xu ◽  
Kesang Li ◽  
Changfeng Song ◽  
Xiaotong Wang ◽  
Yueqi Li ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Bioinformatics Analysis ◽  
Tumor Model ◽  
Downstream Target ◽  
Normal Tissues ◽  
Liver Cancer Cells ◽  
Gene And Protein Expression ◽  
Cancer Tissues

Abstract Background: Liver cancer is a frequent malignancy with poor prognosis. It has been reported that many lncRNAs could regulate the progression of liver cancer. To identify potential therapeutic targets for liver cancer, we conducted bioinformatics analysis of lncRNAs in tumor tissues and adjacent normal tissues. Methods: The differential expression of lncRNAs between liver cancer tissues and adjacent normal tissues were examined by bioinformatics analysis. Cell proliferation was tested by CCK-8. Cell apoptosis in liver cancer was detected by flow cytometry. Gene and protein expression in liver cancer cells were measured by q-PCR and Western-blot, respectively. Xenograft tumor model was established to verify the function of LINC01234 on liver cancer in vivo.Results: LINC01234 was found to be notably upregulated in liver cancer tissues. In addition, knockdown of LINC01234 significantly inhibited the proliferation, invasion and induced the apoptosis of liver cancer cells. Meanwhile, miR-513a-5p was a downstream target of LINC01234 and USP4 was a direct target of miR-513a-5p. Moreover, downregulation of LINC01234 inhibited the tumorigenesis of liver cancer via inactivating TGF-β signaling.Conclusion: Downregulation of LINC01234 could inhibit the progression of liver cancer. Thus, LINC01234 may serve as a potential novel target for treatment of liver cancer.

scholarly journals Ascorbic Acid Inhibits Liver Cancer Growth and Metastasis in vitro and in vivo, Independent of Stemness Gene Regulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Wan ◽  
Juan Zhou ◽  
Lu Fu ◽  
Yubin Li ◽  
Huawu Zeng ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Gene Regulation ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Liver Cancer Cells ◽  
Induced Apoptosis ◽  
Xenotransplantation Model

Experimental and clinical evidence has indicated that the natural product ascorbic acid (AA) is effective in preventing and treating various types of cancers. However, the effect of AA on liver cancer metastasis has not yet been reported. Cancer stem cells (CSCs) play pivotal roles in cancer metastasis. Here, we demonstrated that AA selectively inhibited the viability of both liver cancer cells and CSCs, reduced the formation of cancer cell colonies and CSC spheres, and inhibited tumor growth in vivo. Additionally, AA prevented liver cancer metastasis in a xenotransplantation model without suppressing stemness gene expression in liver CSCs. Further study indicated that AA increased the concentration of H2O2 and induced apoptosis in liver CSCs. Catalase attenuated the inhibitory effects of AA on liver CSC viability. In conclusion, AA inhibited the viability of liver CSCs and the growth and metastasis of liver cancer cells in vitro and in vivo by increasing the production of H2O2 and inducing apoptosis. Our findings provide evidence that AA exerts its anti-liver cancer efficacy in vitro and in vivo, in a manner that is independent of stemness gene regulation.

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