scholarly journals Three New Iridoid Derivatives Have Been Isolated from the Stems of Neonauclea reticulata (Havil.) Merr. with Cytotoxic Activity on Hepatocellular Carcinoma Cells

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2297 ◽  
Author(s):  
Fang-Pin Chang ◽  
Wei Chao ◽  
Sheng-Yang Wang ◽  
Hui-Chi Huang ◽  
Ping-Jyun Sung ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Abscisic Acid ◽  
Cytotoxic Activity ◽  
Spectroscopic Data ◽  
Carcinoma Cells ◽  
Coumaric Acid ◽  
Cytotoxic Assay ◽  
Hep3b Cells ◽  
Hcc Cells

Three new iridoids, namely neonanin A (1), neonanin B (2) and neoretinin A (3), as well as twelve known compounds, 6-hydroxy-7-methyl-1-oxo-4-carbomethoxyoctahydrocyclopenta[c]pyran (4), 4-epi-alyxialactone (5), loganetin (6), loganin (7), phenylcoumaran-α′-aldehyde (8), cleomiscosin A (9), ficusal (10), balanophonin (11), vanillic acid (12), p-coumaric acid (13), cis,trans-abscisic acid (14), and trans,trans-abscisic acid (15) were isolated from the stems of Neonauclea reticulata (Havil.) Merr. These new structures were determined by the detailed analysis of spectroscopic data and comparison with the data of known analogues. Compounds 1–13 were evaluated using an in-vitro MTT cytotoxic assay for hepatocellular carcinoma (HCC) cells, and the preliminary results showed that ficusal (10), balanophonin (11), and p-coumaric acid (13) exhibited moderate cytotoxic activity, with EC50 values of 85.36 ± 4.36, 92.63 ± 1.41, and 29.18 ± 3.48 µg/mL against Hep3B cells, respectively.

scholarly journals Cytotoxic Activity of Anticancer Drugs on Hepatocellular Carcinoma Cells in Hypoxic-Hyponutritional Culture

2014 ◽  
Vol 99 (6) ◽  
pp. 745-752 ◽  
Author(s):  
Qiang Li ◽  
Lin-Zhong Zhu ◽  
Ren-Jie Yang ◽  
Xu Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cytotoxic Activity ◽  
Anticancer Drugs ◽  
Culture Medium ◽  
Carcinoma Cells ◽  
Diphenyltetrazolium Bromide ◽  
Pemetrexed Disodium ◽  
Higher Sensitivity ◽  
Arterial Chemoembolization

Abstract To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect.

scholarly journals Kruppel-like factor 6 suppresses growth and invasion of hepatocellular carcinoma cells in vitro and in vivo

2016 ◽  
Vol 29 (4) ◽  
pp. 666-675 ◽  
Author(s):  
Pei-Hao Wen ◽  
Dong-Yu Wang ◽  
Jia-Kai Zhang ◽  
Zhi-Hui Wang ◽  
Jie Pan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Tumor Model ◽  
Carcinoma Cells ◽  
Tumor Suppressive Function ◽  
Xenograft Tumor Growth ◽  
Hcc Cells

Kruppel-like factor 6 (KLF6) as a novel tumor suppressive gene participates in multiple biological behaviors and plays an important role in regulating tumor cell growth and invasion. However, the functions of KLF6 in hepatocellular carcinoma (HCC) remain poorly understood. The expression level of KLF6 was examined by immunohistochemical assay in human HCC tissues, and KLF6-overexpressed HCC cells (SMCC-7721 and HepG2) were used for evaluating cell proliferation and invasion by MTT and Transwell assays. A subcutaneous HCC tumor model was established for assessing tumor growth in vivo. Our results showed that the expression of KLF6 was significantly downregulated in HCC tissues compared with the adjacent non-cancerous tissues (50.0% vs. 72.0%, P = 0.034) and negatively associated with the lymph-vascular space invasion (LVSI) in HCC patients ( P = 0.003). Furthermore, overexpression of KLF6 reduced cell proliferation and weakened the cell invasive potential followed with the decreased expression of PCNA and MMP-9 in HCC cells. The in vivo experiment indicated that KLF6 overexpression suppressed the xenograft tumor growth. Therefore, our findings show that KLF6 suppresses growth and invasion of HCC cells in vitro and in vivo, suggesting a tumor suppressive function in HCC and provides the potential therapeutic target for the treatment of HCC.

scholarly journals Polyisoprenylated Acylphloroglucinols from Garcinia nervosa

2018 ◽  
Vol 13 (3) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
Alfarius Eko Nugroho ◽  
Hitomi Nakamura ◽  
Daisuke Inoue ◽  
Yusuke Hirasawa ◽  
Chin Piow Wong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cytotoxic Activity ◽  
Spectroscopic Data ◽  
Human Lung ◽  
Carcinoma Cells ◽  
Breast Adenocarcinoma ◽  
Human Breast ◽  
Human Breast Adenocarcinoma ◽  
Human Hepatocellular Carcinoma Cells ◽  
Mcf 7

Two new polyisoprenylated acylphloroglucinols, 7- epi-isoxanthochymol and 7- epi-cycloxanthochymol (1 – 2), were isolated from the barks of Garcinia nervosa together with their 7-epimers isoxanthochymol (3) and cycloxanthochymol (4). Their structures were determined on the basis of NMR spectroscopic data. The cytotoxic activity of the isolated compounds against HL-60, MCF-7 (human breast adenocarcinoma), A549 (human lung adenocarcinoma) and HepG2 (human hepatocellular carcinoma) cells were evaluated, and all compounds showed cytotoxic activity against all cell lines.

scholarly journals SRSF1 promotes the inclusion of exon 3 of SRA1 and the invasion of hepatocellular carcinoma cells by interacting with exon 3 of SRA1pre-mRNA

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sijia Lei ◽  
Bin Zhang ◽  
Luyuan Huang ◽  
Ziyou Zheng ◽  
Shaohan Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Invasion ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Rt Pcr ◽  
Regulated Expression ◽  
Rna Immunoprecipitation ◽  
Hcc Cells

AbstractSteroid receptor RNA activator 1 (SRA1) has been described as a novel transcriptional co-activator that affects the migration of cancer cells. Through RT-PCR, we identified that skipping exon 3 of SRA1 produces two isoforms, including the truncated short isoform, SRA1-S, and the long isoform, SRA1-L. However, the effect of these two isomers on the migration of HCC cells, as well as the specific mechanism of exon 3 skipping remain unclear. In this study, we found up regulated expression of SRSF1 and SRA1-L in highly metastatic HCCLM3, as well as in HCCs with SRSF1 demonstrating the strongest correlation with SRA1-L. In contrast, we observed a constitutively low expression of SRA1-S and SRSF1 in lowly metastatic HepG2 cells. Overexpression of SRSF1 or SRA1-L promoted migration and invasion by increasing the expression of CD44, while SRA1-S reversed the effect of SRSF1 and SRA1-L in vitro. In addition, lung metastasis in mice revealed that, knockdown of SRSF1 or SRA1-L inhibited the migration of HCC cells, while SRA1-L overexpression abolished the effect of SRSF1 knockout and instead promoted HCC cells migration in vivo. More importantly, RNA immunoprecipitation and Cross-link immunoprecipitation analyses showed that SRSF1 interacts with exon 3 of SRA1 to up regulate the expression of SRA1-L in HCC cells. RNA pull-down results indicated that SRSF1 could also bind to exon 3 of SRA1 in vitro. Finally, minigene -MS2 mutation experiments showed that mutation of the SRA1 exon 3 binding site for SRSF1 prevented the binding of SRA1 pre-mRNA. In summary, our results provide experimental evidence that SRA1 exon 3 inclusion is up regulated by SRSF1 to promote tumor invasion and metastasis in hepatocellular carcinoma.

scholarly journals Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells

2021 ◽  
Vol 22 (10) ◽  
pp. 5330
Author(s):  
Yeonghoon Son ◽  
Na-Rae Shin ◽  
Sung-Ho Kim ◽  
Su-Cheol Park ◽  
Hae-June Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
Colony Formation ◽  
Anticancer Therapy ◽  
Carcinoma Cells ◽  
Hep3b Cells ◽  
Human Hepatocellular Carcinoma Cells ◽  
Systemic Drug ◽  
Higher Sensitivity ◽  
Hcc Cells

Despite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy.

Oral administration of EGCG solution equivalent to daily achievable dosages of regular tea drinkers effectively suppresses miR483-3p induced metastasis of hepatocellular carcinoma cells in mice

2021 ◽  
Author(s):  
Qingzheng Kang ◽  
Yin Tong ◽  
Vemana Gowd ◽  
Mingfu Wang ◽  
Feng Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Oral Administration ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Hepatocellular Carcinoma Cells ◽  
Hcc Cells

The effect of non-cytotoxic doses of epigallocatechin-3-gallate (EGCG) on the metastatic capability of human hepatocellular carcinoma (HCC) cells was investigated in vitro and in vivo. miR483-3p, a microRNA whose expression...

Sufentanil Inhibits Proliferation, Migration, and Invasion of Hepatocellular Carcinoma Cells by Upregulating miRNA-204

2021 ◽  
Vol 11 (4) ◽  
pp. 718-724
Author(s):  
Jiuwu Zhuo ◽  
Yishan Zheng ◽  
Wanying Hu ◽  
Guoping Yin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Biological Function ◽  
Transfection Efficiency ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Qrt Pcr ◽  
Pi3k Signaling Pathway ◽  
Hep3b Cells ◽  
Underlying Mechanisms ◽  
Hcc Cells

Sufentanil is a powerful analgesic that acts on μ-receptors, but there are few studies on sufentanil in cancer. The biological function and underlying mechanisms of sufentanil on the hepatocellular carcinoma (HCC) cells were explored in the present study. HCC cells were first treated with different concentrations of sufentanil and the most optimum concentration of sufentanil was determined. The expression of miR-204 in HCC cells was changed by transfected with miR-204 inhibitor and the transfection efficiency was assessed by qRT-PCR. CCK-8, wound-healing and Transwell assays were performed to evaluate the proliferation, migration and invasion of HCC cells, respectively. The level of AKT and PI3K phosphorylation (p-AKT and p-PI3K) were assessed by western blot analysis. Our results demonstrated that sufentanil effectively inhibited cell proliferation,migration and invasion in both Huh7 and Hep3B cells, and significantly decreased the expression of p-AKT and p-PI3K. In addition, miR-204 was upregulated in Huh7 and Hep3B cells treated with sufentanil, and low expression of miR-204 attenuated the damage of sufentanil on the viability of Huh7 and Hep3B cells. Taken together, sufentanil suppressed the proliferation, migration and invasion of HCC cells via inhibiting AKT/PI3K signaling pathway by targeting miR-204.

Radiofrequency ablation triggers the migration of hepatocellular carcinoma cells by suppressing miR-148a-5p

2020 ◽  
Vol 401 (8) ◽  
pp. 985-994
Author(s):  
Haicun Wang ◽  
Yang Cao ◽  
Kaiwen Hu ◽  
Quanwang Li ◽  
Yufei Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Carcinoma Cells ◽  
Ataxia Telangiectasia Mutated ◽  
Mesenchymal Transition ◽  
Insufficient Radiofrequency Ablation ◽  
Hcc Cells

AbstractIncreasing evidences suggest that insufficient radiofrequency ablation (IRFA) can paradoxically promote tumor invasion and metastatic processes, whereas the effects of moderate hyperthermia on cancer progression are not well illustrated. Our study found that IRFA can increase the in vitro migration, invasion, and epithelial–mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells via induction of Snail, a master regulator of EMT events. Among measured miRNAs, IRFA can decrease the expression of miR-148a-5p in HCC cells. Whereas overexpression of miR-148a-5p can reverse IRFA-induced migration of HCC cells and upregulation of Snail, mechanistically overexpression of miR-148a-5p can directly target and decrease the expression of protein kinase ATM (ataxia telangiectasia mutated), which can increase protein stability of Snail. Collectively, our data suggest that IRFA can regulate the miR-148a-5p/ATM/Snail axis to trigger migration of HCC cells.

scholarly journals Anthocyanins Derived from Vitis coignetiae Pulliat Contributes Anti-Cancer Effects by Suppressing NF-κB Pathways in Hep3B Human Hepatocellular Carcinoma Cells and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5445
Author(s):  
Min Jeong Kim ◽  
Anjugam Paramanantham ◽  
Won Sup Lee ◽  
Jeong Won Yun ◽  
Seong Hwan Chang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Hepatocellular Carcinoma Cells ◽  
In Vivo Experiments ◽  
Anti Cancer ◽  
Hep3b Cells ◽  
Human Hepatocellular Carcinoma Cells

We previously demonstrated that anthocyanins from the fruits of Vitis coignetiae Pulliat (AIMs) induced the apoptosis of hepatocellular carcinoma cells. However, many researchers argued that the concentrations of AIMs were too high for in vivo experiments. Therefore, we performed in vitro at lower concentrations and in vivo experiments for the anti-cancer effects of AIMs. AIMs inhibited the cell proliferation of Hep3B cells in a dose-dependent manner with a maximum concentration of 100 µg/mL. AIMs also inhibited the invasion and migration at 100 µg/mL concentration with or without the presence of TNF-α. To establish the relevance between the in vitro and in vivo results, we validated their effects in a Xenograft model of Hep3B human hepatocellular carcinoma cells. In the in vivo test, AIMs inhibited the tumorigenicity of Hep3B cells in the xenograft mouse model without showing any clinical signs of toxicity or any changes in the body weight of mice. AIMs inhibited the activation NF-κB and suppressed the NF-κB-regulated proteins, intra-tumoral microvessel density (IMVD) and the Ki67 activity of Hep3B xenograft tumors in athymic nude mice. In conclusion, this study indicates that AIMs have anti-cancer effects (inhibition of proliferation, invasion, and angiogenesis) on human hepatocellular carcinoma xenograft through the inhibition of NF-κB and its target protein.

scholarly journals BNIP3L-Dependent Mitophagy Promotes HBx-Induced Cancer Stemness of Hepatocellular Carcinoma Cells via Glycolysis Metabolism Reprogramming

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 655 ◽  
Author(s):  
Yuan-Yuan Chen ◽  
Wei-Hua Wang ◽  
Lin Che ◽  
You Lan ◽  
Li-Yin Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Energy Homeostasis ◽  
Side Population ◽  
Carcinoma Cells ◽  
Cancer Stemness ◽  
B Virus ◽  
Hcc Cells

Hepatitis B virus (HBV) is one of predisposing factors for hepatocellular carcinoma (HCC). The role of HBV x protein (HBx) in mediating the induction and maintenance of cancer stemness during HBV-related HCC attracts considerable attention, but the exact mechanism has not been clearly elucidated. Here, ABCG2-dependent stem-like side population (SP) cells, which are thought to be liver cancer stem cells (LCSCs), were present in HCC cells, and the fraction of this subset was increased in HBx-expressing HCC cells. In addition, glycolysis was upregulated in LCSCs and HBx-expressing HCC cells, and intervention of glycolysis attenuated cancer stem-like phenotypes. Mitochondria play an important role in the maintenance of energy homeostasis, BNIP3L-dependent mitophagy was also activated in LCSCs and HBx-expressing HCC cells, which triggered a metabolic shift toward glycolysis. In summary, we proposed a positive feedback loop, in which HBx induced BNIP3L-dependent mitophagy which upregulated glycolytic metabolism, increasing cancer stemness of HCC cells in vivo and in vitro. BNIP3L might be a potential therapeutic target for intervention of LCSCs-associated HCC. Anti-HBx, a monoclonal antibody targeting intracellular HBx, had the potential to delay the progression of HBV infection related-HCC.

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