scholarly journals Selective Anti-Cancer Effects of Plasma-Activated Medium and Its High Efficacy with Cisplatin on Hepatocellular Carcinoma with Cancer Stem Cell Characteristics

2021 ◽  
Vol 22 (8) ◽  
pp. 3956
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Hae June Lee ◽  
Kiwon Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cell Lines ◽  
Primary Liver Cancer ◽  
Atmospheric Pressure Plasma ◽  
Normal Liver ◽  
Normal Liver Cell ◽  
Ample Evidence ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and -independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.

scholarly journals Cold Atmospheric Pressure Plasma-Activated Medium Induces Selective Cell Death in Human Hepatocellular Carcinoma Cells Independently of Singlet Oxygen, Hydrogen Peroxide, Nitric Oxide and Nitrite/Nitrate

2021 ◽  
Vol 22 (11) ◽  
pp. 5548
Author(s):  
Yan Li ◽  
Tianyu Tang ◽  
Haejune Lee ◽  
Kiwon Song
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Singlet Oxygen ◽  
Atmospheric Pressure ◽  
Atmospheric Pressure Plasma ◽  
Proliferative Effect ◽  
Huh7 Cells ◽  
Anti Cancer ◽  
Cold Atmospheric Pressure Plasma ◽  
Nitrite Nitrate

Cold atmospheric pressure plasma (CAP) and plasma-activated medium (PAM) induce cell death in diverse cancer cells and may function as powerful anti-cancer agents. The main components responsible for the selective anti-cancer effects of CAP and PAM remain elusive. CAP or PAM induces selective cell death in hepatocellular carcinoma cell lines Hep3B and Huh7 containing populations with cancer stem cell markers. Here, we investigated the major component(s) of CAP and PAM for mediating the selective anti-proliferative effect on Hep3B and Huh7 cells. The anti-proliferative effect of CAP was mediated through the medium; however, the reactive oxygen species scavenger N-acetyl cysteine did not suppress PAM-induced cell death. Neither high concentrations of nitrite or nitrite/nitrate nor a low concentration of H2O2 present in the PAM containing sodium pyruvate affected the viability of Hep3B and Huh7 cells. Inhibitors of singlet oxygen, superoxide anions, and nitric oxide retained the capacity of PAM to induce anti-cancer effects. The anti-cancer effect was largely blocked in the PAM prepared by placing an aluminum metal mesh, but not a dielectric PVC mesh, between the plasma source and the medium. Hence, singlet oxygen, hydrogen peroxide, nitric oxide, and nitrite/nitrate are not the main factors responsible for PAM-mediated selective death in Hep3B and Huh7 cells. Other factors, such as charged particles including various ions in CAP and PAM, may induce selective anti-cancer effects in certain cancer cells.

Decreased expression of long non-coding LOC285194 predicts tumour progression and poor prognosis of hepatocellular carcinoma after curative hepatectomy

2019 ◽  
Vol 96 (1132) ◽  
pp. 79-83 ◽  
Author(s):  
Jianguo Qiu ◽  
Gang Pan ◽  
Ming Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Poor Prognosis ◽  
Tumour Progression ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Expression Level ◽  
Term Survival ◽  
Normal Liver Cell ◽  
Low Expression

BackgroundLong non-coding RNAs (LncRNAs) have been recently implicated as having oncogenic and tumour suppressor roles. LncRNA LOC285194 (LOC285194) expression was significantly reduced in a variety of tumour tissues and cell lines, which promotes cell proliferation and migration. The aim of the present study is to examine the expression pattern of LOC285194 and its clinical significance in hepatocellular carcinoma (HCC) patients after curative liver resection.Materials and methodsWe examined the expression of LOC285194 in 120 HCC samples and controls from adjacent non-tumour tissues using real-time quantitative reverse transcription-PCR and analysed its correlation with clinical parameters and prognosis in these patients who have undergone curative hepatic resection with a median follow-up of 3.5 years.ResultsThe expression level of LOC285194 was significantly lower in tumour tissues and four liver cancer cell lines compared with adjacent normal tissues and normal liver cell line. Furthermore, a low expression of LOC285194 was significantly correlated with advanced tumour stage, microvascular invasion, tumour number and differentiation. Additionally, survival analysis showed that patients with low LOC285194 expression had a significantly worse overall and disease-free survival. Moreover, univariate and multivariate analyses showed that decreased expression of LOC285194 was an independent predictor of long-term survival.ConclusionsThe low expression level of LOC285194 might be a novel candidate biomarker for predicting tumour progression and poor prognosis in HCC patients who have undergone hepatectomy and might be a potential target for gene therapy.

scholarly journals LncRNA MEG3 affects cell proliferation, apoptosis and migration by targeting miR-9-5p/MDK axis and activating PDK/AKT pathway in hepatocellular carcinoma

2020 ◽  
Author(s):  
Dezhi Wu ◽  
Zheng Ma ◽  
Deyu Ma ◽  
Qiquan Li
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Normal Liver ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Normal Liver Cell ◽  
Non Coding Rna ◽  
And Migration

Abstract Background Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3) was supposed to be a tumor suppressor in various cancers. However, the role of MEG3 in hepatocellular carcinoma (HCC) and the related molecular mechanisms are not well illustrated. This study aimed to determine the biological function of MEG3 in regulating HCC cell proliferation, apoptosis and migration. Moreover, the interaction among MEG3, microRNA (miR)-9-5p and Midkine (MDK), and the activation of phosphoinositide-dependent kinase (PDK)/AKT pathway in HCC cells were examined. Methods and Results Expression of MEG3 in a series of liver cancer cell lines was detected by RT-qPCR. Luciferase reporter assay, RT-qPCR and western blot were used to determine the interaction among MEG3, miR-9-5p and MDK, and the activation of PDK/AKT pathway. Cell proliferation and apoptosis were evaluated by CCK8, flow cytometry analysis for cell cycle and apoptosis, and Caspase 3/9 activity. Cell migration was determined by wound healing assay and MMP1 expression. We found MEG3 was decreased in HCC cell lines compared with the normal liver cell line. MEG3 suppressed HCC cell proliferation and migration, and induced cell apoptosis. Further, we found MEG3 targets miR-9-5p/MDK axis and modulates PDK/AKT pathway in HCC. Conclusion Our findings demonstrated that lncRNA MEG3 affects HCC cell proliferation, apoptosis and migration through its targeting of miR-9-5p/MDK and regulating of PDK/AKT pathway. This study suggested MEG3/miR-9-5p/MDK axis as the potential therapeutic target in HCC.

scholarly journals TGF-β1 Promotes Hepatocellular Carcinoma Invasion and Metastasis via ERK Pathway-Mediated FGFR4 Expression

2018 ◽  
Vol 45 (4) ◽  
pp. 1690-1699 ◽  
Author(s):  
Jiawei Huang ◽  
Mengyuan Qiu ◽  
Li Wan ◽  
Gui Wang ◽  
Tongzhou Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Western Blot ◽  
Cell Lines ◽  
Normal Liver ◽  
Erk Pathway ◽  
Invasion And Metastasis ◽  
Normal Liver Cell ◽  
Tgf Β1

Background/Aims: TGF-β1 is beneficial during early liver disease but is tumor-progressive during late stages especially for hepatocellular carcinoma (HCC). Thus, exploring the underlying mechanisms may provide information about a potentially therapeutic role of TGF-β1 in HCC. Methods: Western blot and real-time quantitative PCR were used to quantify FGFR4 expression in HCC cell lines and a normal liver cell line. After constructing the best silencing FGFR4 expression vector, migration and invasiveness of TGF-β1 in HCC was studied in vitro and in vivo. Western blot was used to study the mechanism of TGF-β1 induction on FGFR4 expression with various inhibitors. Results: HepG2 cell lines had the most FGFR4 expression, and data show that silencing FGFR4 suppressed cell proliferation, invasion and migration in HCC induced by TGF-β1 in vitro and in vivo. Moreover, TGF-β1 induced FGFR4 expression through the ERK pathway. Conclusion: Promoting FGFR4 expression via the ERK pathway, TGF-β1 contributes to HCC invasion and metastasis.

scholarly journals 3,3′-Diindolylmethane Suppresses the Growth of Hepatocellular Carcinoma by Regulating Its Invasion, Migration and ER Stress-Mediated Mitochondrial Apoptosis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1178
Author(s):  
Suvesh Munakarmi ◽  
Juna Shrestha ◽  
Hyun-Beak Shin ◽  
Geum-Hwa Lee ◽  
Yeon-Jun Jeong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Er Stress ◽  
Hepatoma Cell ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide with limited treatment options. Biomarker-based active phenolic flavonoids isolated from medicinal plants might shed some light on potential therapeutics for treating HCC. 3,3′-diindolylmethane (DIM) is a unique biologically active dimer of indole-3-carbinol (I3C), a phytochemical compound derived from Brassica species of cruciferous vegetables—such as broccoli, kale, cabbage, and cauliflower. It has anti-cancer effects on various cancers such as breast cancer, prostate cancer, endometrial cancer, and colon cancer. However, the molecular mechanism of DIM involved in reducing cancer risk and/or enhancing therapy remains unknown. The aim of the present study was to evaluate anti-cancer and therapeutic effects of DIM in human hepatoma cell lines Hep3B and HuhCell proliferation was measured with MTT and trypan blue colony formation assays. Migration, invasion, and apoptosis were measured with Transwell assays and flow cytometry analyses. Reactive oxygen species (ROS) intensity and the loss in mitochondrial membrane potential of Hep3B and Huh7 cells were determined using dihydroethidium (DHE) staining and tetramethylrhodamine ethyl ester dye. Results showed that DIM significantly suppressed HCC cell growth, proliferation, migration, and invasion in a concentration-dependent manner. Furthermore, DIM treatment activated caspase-dependent apoptotic pathway and suppressed epithelial–mesenchymal transition (EMT) via ER stress and unfolded protein response (UPR). Taken together, our results suggest that DIM is a potential anticancer drug for HCC therapy by targeting ER-stress/UPR.

scholarly journals Anti-Cancer Effects of Glaucarubinone in the Hepatocellular Carcinoma Cell Line Huh7 via Regulation of the Epithelial-To-Mesenchymal Transition-Associated Transcription Factor Twist1

2021 ◽  
Vol 22 (4) ◽  
pp. 1700
Author(s):  
Jihye Seo ◽  
Jain Ha ◽  
Eunjeong Kang ◽  
Haelim Yoon ◽  
Sewoong Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Wound Healing ◽  
Transcription Factor ◽  
Cell Migration ◽  
Cell Line ◽  
Intracellular Signaling ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
Anti Cancer

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is a leading cause of cancer-related deaths. As HCC has a high mortality rate and its incidence is increasing worldwide, understanding and treating HCC are crucial for resolving major public health concerns. In the present study, wound healing screening assays were performed using natural product libraries to identify natural chemicals that can inhibit cancer cell migration. Glaucarubinone (GCB) showed a high potential for inhibiting cell migration. The anti-cancer effects of GCB were evaluated using the HCC cell line, Huh7. GCB showed anti-cancer effects, as verified by wound healing, cell migration, invasion, colony formation, and three-dimensional spheroid invasion assays. In addition, cells treated with GCB showed suppressed matrix metalloproteinase activities. Immunoblotting analyses of intracellular signaling pathways revealed that GCB regulated the levels of Twist1, a crucial transcription factor associated with epithelial-to-mesenchymal transition, and mitogen-activated protein kinase. The invasive ability of cancer cells was found to be decreased by the regulation of Twist1 protein levels. Furthermore, GCB downregulated phosphorylation of extracellular signal-regulated kinase. These results indicate that GCB exhibits anti-metastatic properties in Huh7 cells, suggesting that it could be used to treat HCC.

scholarly journals The Comprehensive Roles of ATRANORIN, A Secondary Metabolite from the Antarctic Lichen Stereocaulon caespitosum, in HCC Tumorigenesis

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1414 ◽  
Author(s):  
Young-Jun Jeon ◽  
Sanghee Kim ◽  
Ji Hee Kim ◽  
Ui Joung Youn ◽  
Sung-Suk Suh
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Genetic Diseases ◽  
Annexin V ◽  
Cancer Therapeutics ◽  
Metastatic Potential ◽  
Anti Cancer ◽  
Experimental Approaches ◽  
The Antarctic ◽  
Death Determination

Hepatocellular carcinoma (HCC) is one of the most deadly genetic diseases, but surprisingly chemotherapeutic approaches against HCC are only limited to a few targets. In particular, considering the difficulty of a chemotherapeutic drug development in terms of cost and time enforces searching for surrogates to minimize effort and maximize efficiency in anti-cancer therapy. In spite of the report that approximately one thousand lichen-derived metabolites have been isolated, the knowledge about their functions and consequences in cancer development is relatively limited. Moreover, one of the major second metabolites from lichens, Atranorin has never been studied in HCC. Regarding this, we comprehensively analyze the effect of Atranorin by employing representative HCC cell lines and experimental approaches. Cell proliferation and cell cycle analysis using the compound consistently show the inhibitory effects of Atranorin. Moreover, cell death determination using Annexin-V and (Propidium Iodide) PI staining suggests that it induces cell death through necrosis. Lastly, the metastatic potential of HCC cell lines is significantly inhibited by the drug. Taken these together, we claim a novel functional finding that Atranorin comprehensively suppresses HCC tumorigenesis and metastatic potential, which could provide an important basis for anti-cancer therapeutics.

scholarly journals Increased ERp57 Expression in HBV-Related Hepatocellular Carcinoma: Possible Correlation and Prognosis

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Miao Liu ◽  
Lingyao Du ◽  
Zhiliang He ◽  
Libo Yan ◽  
Ying Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B ◽  
Cell Line ◽  
Cell Lines ◽  
Liver Cell ◽  
Normal Liver ◽  
Hbv Infection ◽  
Altered Expression ◽  
Liver Cell Line ◽  
Liver Tissues

Aim.ERp57 is involved in virus induced endoplasmic reticulum stress (ERS) and plays an important role in tumorigenesis. This study aimed to find whether HBV infection altered ERp57 expression and whether ERp57 regulation was involved in hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) genesis.Materials and Methods.HBV-HCC tissues, chronic hepatitis B (CHB) liver tissues, and normal liver tissues were acquired. ERp57 expressions in these tissues were detected through immunohistochemistry (IHC). And ERp57 expression in liver cell line L02, HBV replicative liver cell line L02-pHBV4.1, and HCC cell lines were detected through western blot for verification. Then medical data on patients providing HCC tissues were collected and analyzed along with ERp57 expression.Results.Higher ERp57 expression was found in HCC and CHB tissues (p<0.001). And HCC cell lines and L02-pHBV4.1 presented higher ERp57 expression as well. In patients, ERp57 expression showed significant differences between death and survival groups (p=0.037). And cumulative survival in patients with higher ERp57 (score⩾8.75) is significantly lower (p=0.009).Conclusion.Our study found increased expression of ERp57 in HBV-HCC. Such altered expression could be related to HBV infection and high ERp57 expression may lead to poor prognosis of HBV-HCC patients.

Artocarpus communis Induces Autophagic Instead of Apoptotic Cell Death in Human Hepatocellular Carcinoma Cells

2015 ◽  
Vol 43 (03) ◽  
pp. 559-579 ◽  
Author(s):  
Cheng-Wei Tzeng ◽  
Wen-Sheng Tzeng ◽  
Liang-Tzung Lin ◽  
Chiang-Wen Lee ◽  
Ming-Hong Yen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Hepatoma Cell ◽  
Apoptotic Cell Death ◽  
Human Hepatocellular Carcinoma ◽  
Acridine Orange Staining ◽  
Hepatoma Cell Lines

For centuries, natural plant extracts have played an important role in traditional medicine for curing and preventing diseases. Studies have revealed that Artocarpus communis possess various bioactivities, such as anti-inflammation, anti-oxidant, and anticancer activities. A. communis offers economic value as a source of edible fruit, yields timber, and is widely used in folk medicines. However, little is known about its molecular mechanisms of anticancer activity. Here, we demonstrate the antiproliferative activity of A. communis methanol extract (AM) and its dichloromethane fraction (AD) in two human hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay showed the long-term inhibitory effect of both extracts on cell growth. DNA laddering and immunoblotting analyses revealed that both extracts did not induce apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated different cell cycle distribution compared to UV-treated cells, which presented apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining revealed that AM and AD triggered autophagosome accumulation. Immunoblotting showed a significant expression of autophagy-related proteins, which indicated the autophagic cell death (ACD) of hepatoma cell lines. This study therefore demonstrates that A. communis AM and its dichloromethane fraction can induce ACD in HCC cells and elucidates the potential of A. communis extracts for development as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating cancer cell death.

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