scholarly journals Role of antioxidants in the treatment of hepatocellular carcinoma: Integrative review

2021 ◽  
Vol 10 (1) ◽  
pp. e46310112028
Author(s):  
Claudriana Locatelli ◽  
Joyce Kelly Busolin Jardim ◽  
Vilmair Zancanaro
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radical Scavenging Activity ◽  
Treatment Options ◽  
Radical Scavenging ◽  
Integrative Review ◽  
Advanced Hepatocellular Carcinoma ◽  
Rate Dependent

Theorical framework: Hepatocellular carcinoma is a unique cancer that typically arises in the setting of chronic liver disease at a rate dependent upon the complex interplay between the host, disease, and environmental factors. Unfortunately, with contemporary management, patients with advanced hepatocellular carcinoma have few treatment options, and the prognosis is poor. Objective: Evaluate the role of antioxidants in the treatment of hepatocellular carcinoma. Methodology: It is an integrative review, with a qualitative approach. Based on research on ScienceDirect and PubMed databases, 12 articles were selected that were consistent with the theme and the inclusion and exclusion criteria, through the association of descriptors and keywords. Results: Studies in vivo demonstrated a positive correlation of antioxidants in the treatment of hepatocellular carcinoma. The antioxidants were able to promote inhibition of development tumor through promotes decrease of proinflammatory cytokines IL-1 and IL-6 and changes the ratios of Bax/Bcl2 that supports apoptosis. In oxidative stress, may be able to direct free radical scavenging activity. Among the main antioxidants with advanced preclinical evidence in the treatment of hepatocellular carcinoma is curcumin with tests in humans, and gallic acid, quercetin and resveratrol with several tests in vitro and in vivo. Conclusion: This study highlights that antioxidants can be a promising therapy in the treatment of hepatocellular carcinoma.

scholarly journals MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

2021 ◽  
Author(s):  
Ting Yu ◽  
Jiajian Yu ◽  
Lu Lu ◽  
Yize Zhang ◽  
Yadong Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Feedback Loop ◽  
Carcinoma Cells ◽  
Advanced Hepatocellular Carcinoma ◽  
Apoptotic Protein ◽  
Non Coding Rnas ◽  
Hcc Cells

Abstract Purpose Lenvatinib is a long-awaited alternative to Sorafenib for first-line targeted therapy of patients with advanced hepatocellular carcinoma (HCC). However, resistance to Lenvatinib results in tumor progression and has become a major obstacle to improving the prognosis of HCC patients. Exploring the mechanisms underlying Lenvatinib resistance is considered essential for the treatment of advanced HCC. Methods Lenvatinib resistant HCC (LR-HCC) cells were generated and potential long non-coding RNAs (Lnc-RNAs) upregulated in LR-HCC cells were identified by RNA sequencing. The effects of upregulated Lnc-RNAs were evaluated in vitro in cell models and in vivo in experimental animals using quantitative cell viability and apoptosis assays. Results We found that Lnc-RNA MT1JP (MT1JP) was upregulated in LR-HCC cells and inhibited the apoptosis signaling pathway. In addition, we found that sponging of microRNA-24-3p by MT1JP released Bcl-2 like 2 (BCL2L2), an anti-apoptotic protein, thereby forming a positive-feedback loop. The role of this feedback loop was validated using rescue assays. Additionally, we found that upregulation of MT1JP and BCL2L2 impaired the sensitivity of HCC cells to Lenvatinib both vitro and vivo. Conclusions Our results suggest a novel molecular feedback loop between MT1JP and apoptosis signaling in Lenvatinib sensitive HCC cells.

Knockout of Ajuba Attenuates the Growth and Migration of Hepatocellular Carcinoma Cells

2020 ◽  
Vol 160 (11-12) ◽  
pp. 650-658
Author(s):  
Yichen Le ◽  
Yi He ◽  
Meirong Bai ◽  
Ying Wang ◽  
Jiaxue Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cancer Progression ◽  
Normal Liver ◽  
Cell Growth And Migration ◽  
And Migration ◽  
Hcc Cells

Ajuba has been found to be mutated or aberrantly regulated in several human cancers and plays important roles in cancer progression via different signaling pathways. However, little is known about the role of Ajuba in hepatocellular carcinoma (HCC). Here, we found an upregulation of Ajuba expression in HCC tissues compared with normal liver tissues, while a poor prognosis was observed in HCC patients with high Ajuba expression. Knockout of Ajuba in HCC cells inhibited cell growth in vitro and in vivo, suppressed cell migration, and enhanced the cell apoptosis under stress. Moreover, re-expression of Ajuba in Ajuba-deficient cells could restore the phenotype of Ajuba-deficient cells. In conclusion, these results indicate that Ajuba is upregulated in HCC and promotes cell growth and migration of HCC cells, suggesting that Ajuba could possibly be a new target for HCC diagnosis and treatment.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Junjie Xu ◽  
Lin Ji ◽  
Yuelong Liang ◽  
Zhe Wan ◽  
Wei Zheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Nuclear Interaction ◽  
Circular Rna ◽  
Advanced Hepatocellular Carcinoma ◽  
Proof Of Concept ◽  
Potential Strategy ◽  
Oncogenic Protein ◽  
Hcc Cells

AbstractSorafenib is the first-line chemotherapeutic therapy for advanced hepatocellular carcinoma (HCC). However, sorafenib resistance significantly limits its therapeutic efficacy, and the mechanisms underlying resistance have not been fully clarified. Here we report that a circular RNA, circRNA-SORE (a circular RNA upregulated in sorafenib-resistant HCC cells), plays a significant role in sorafenib resistance in HCC. We found that circRNA-SORE is upregulated in sorafenib-resistant HCC cells and depletion of circRNA-SORE substantially increases the cell-killing ability of sorafenib. Further studies revealed that circRNA-SORE binds the master oncogenic protein YBX1 in the cytoplasm, which prevents YBX1 nuclear interaction with the E3 ubiquitin ligase PRP19 and thus blocks PRP19-mediated YBX1 degradation. Moreover, our in vitro and in vivo results suggest that circRNA-SORE is transported by exosomes to spread sorafenib resistance among HCC cells. Using different HCC mouse models, we demonstrated that silencing circRNA-SORE by injection of siRNA could substantially overcome sorafenib resistance. Our study provides a proof-of-concept demonstration for a potential strategy to overcome sorafenib resistance in HCC patients by targeting circRNA-SORE or YBX1.

scholarly journals Study of Antimicrobial, Antioxidant and Cytotoxicity Properties of Selected Plant Extracts for Food Preservative Applications

2021 ◽  
pp. 95-111
Author(s):  
Tania Islam ◽  
Md Nazrul Islam ◽  
Wahidu Zzaman ◽  
Md Morsaline Billah
Keyword(s):  
Pathogenic Bacteria ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Antimicrobial Properties ◽  
In Vivo Studies ◽  
Diffusion Method ◽  
Plant Materials ◽  
Food Preservative

An attempt has been made to evaluate antimicrobial, antioxidant and cytotoxicity properties of extracts from onion (Allium cepa L.), garlic (Allium sativum), leaves of guava (Psidium guajava), papaya (Carica papaya), tea (Camellia sinensis), baen (Avicennia alba) and keora (Sonneratia apetala), respectively to apply as natural preservatives for tomatoes. The air-dried plant materials of the respective plant species were subjected to ethanol-methanol extraction, concentrated and stored at 4 °C before use. The extracts were dissolved in 95% ethanol for analysis of antioxidant and antimicrobial properties. Of the extracts tested, tea extracts showed the highest zone of inhibition against several pathogenic bacteria (E. coli 35.0±3.2 mm; P. aeruginosa 29.3±2.6 mm; S. typhi 28.4±2.1 mm and S. pyogenes 27.7±3.7 mm) using the disc diffusion method. In regard to DPPH free radical scavenging assay, keora and guava extracts showed the highest percentage of radical scavenging activity with the values of 89.64± 0.18 and 89.39± 0.88, respectively, which were in agreement with higher total antioxidant capacity (TAC) of these extracts obtained by the phosphomolybdenum method. Brine shrimp lethality bioassay for cytotoxicity assessment showed LC50 of 132.54 ± 18.99 µg/mL for the leaf extract of keora which was found to be most toxic among all studied extracts. The initial results indicated that the extracts could be used for food preservative applications based on the antimicrobial, antioxidant and cytotoxicity properties of the tested extracts. However, efficacy, stability and safety issues need to be addressed with both in vitro and in vivo studies.

scholarly journals A Review of Recent Studies on the Antioxidant Activities of a Third-Millennium Food: Amaranthus spp.

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1236
Author(s):  
Seon-Joo Park ◽  
Anshul Sharma ◽  
Hae-Jeung Lee
Keyword(s):  
Antioxidant Activity ◽  
Bioactive Peptides ◽  
Antioxidant Activities ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Sustainable Food ◽  
Amaranth Species ◽  
Amaranthus Spp

Amaranth (Amaranthus spp.) plant commonly refers to the sustainable food crop for the 21st century. The crop has witnessed significant attention in recent years due to its high nutritional value and agronomic advantages. It is a relatively well-balanced cosmopolitan food that is a protector against chronic diseases. Usually, the antioxidant activities of amaranth are held responsible for its defensive behavior. Antioxidant activity of plants, generally, is attributed to their phytochemical compounds. The current interest, however, lies in hydrolysates and bioactive peptides because of their numerous biological functions, including antioxidant effect. While the importance of bioactive peptides has been progressively recognized, an integrated review of recent studies on the antioxidant ability of amaranth species, especially their hydrolysates and peptides has not been generated. Hence, in this review, we summarize studies focused on the antioxidant capacity of amaranth renewal over the period 2015–2020. It starts with a background and overall image of the amaranth-related published reviews. The current research focusing on in vitro, in vivo, and chemical assays-based antioxidant activity of different amaranth species are addressed. Finally, the last segment includes the latest studies concerning free radical scavenging activity and metal chelation capacity of amaranth protein hydrolysates and bioactive peptides.

scholarly journals Downregulation of CRABP2 Inhibit the Tumorigenesis of Hepatocellular Carcinoma In Vivo and In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Qingmin Chen ◽  
Ludong Tan ◽  
Zhe Jin ◽  
Yahui Liu ◽  
Ze Zhang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Hcc Cells

Cellular retinoic acid-binding protein 2 (CRABP2) binds retinoic acid (RA) in the cytoplasm and transports it into the nucleus, allowing for the regulation of specific downstream signal pathway. Abnormal expression of CRABP2 has been detected in the development of several tumors. However, the role of CRABP2 in hepatocellular carcinoma (HCC) has never been revealed. The current study aimed to investigate the role of CRABP2 in HCC and illuminate the potential molecular mechanisms. The expression of CRABP2 in HCC tissues and cell lines was detected by western blotting and immunohistochemistry assays. Our results demonstrated that the expression levels of CRABP2 in HCC tissues were elevated with the tumor stage development, and it was also elevated in HCC cell lines. To evaluate the function of CRABP2, shRNA-knockdown strategy was used in HCC cells. Cell proliferation, metastasis, and apoptosis were analyzed by CCK-8, EdU staining, transwell, and flow cytometry assays, respectively. Based on our results, knockdown of CRABP2 by shRNA resulted in the inhibition of tumor proliferation, migration, and invasion in vitro, followed by increased tumor apoptosis-related protein expression and decreased ERK/VEGF pathway-related proteins expression. CRABP2 silencing in HCC cells also resulted in the failure to develop tumors in vivo. These results provide important insights into the role of CRABP2 in the development and development of HCC. Based on our findings, CRABP2 may be used as a novel diagnostic biomarker, and regulation of CRABP2 in HCC may provide a potential molecular target for the therapy of HCC.

scholarly journals Tumour initiating cells and IGF/FGF signalling contribute to sorafenib resistance in hepatocellular carcinoma

Gut ◽  
2015 ◽  
Vol 66 (3) ◽  
pp. 530-540 ◽  
Author(s):  
Victoria Tovar ◽  
Helena Cornella ◽  
Agrin Moeini ◽  
Samuel Vidal ◽  
Yujin Hoshida ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Gene Signature ◽  
Signalling Pathways ◽  
Fgf Signalling

ObjectiveSorafenib is effective in hepatocellular carcinoma (HCC), but patients ultimately present disease progression. Molecular mechanisms underlying acquired resistance are still unknown. Herein, we characterise the role of tumour-initiating cells (T-ICs) and signalling pathways involved in sorafenib resistance.DesignHCC xenograft mice treated with sorafenib (n=22) were explored for responsiveness (n=5) and acquired resistance (n=17). Mechanism of acquired resistance were assessed by: (1) role of T-ICs by in vitro sphere formation and in vivo tumourigenesis assays using NOD/SCID mice, (2) activation of alternative signalling pathways and (3) efficacy of anti-FGF and anti-IGF drugs in experimental models. Gene expression (microarray, quantitative real-time PCR (qRT-PCR)) and protein analyses (immunohistochemistry, western blot) were conducted. A novel gene signature of sorafenib resistance was generated and tested in two independent cohorts.ResultsSorafenib-acquired resistant tumours showed significant enrichment of T-ICs (164 cells needed to create a tumour) versus sorafenib-sensitive tumours (13 400 cells) and non-treated tumours (1292 cells), p<0.001. Tumours with sorafenib-acquired resistance were enriched with insulin-like growth factor (IGF) and fibroblast growth factor (FGF) signalling cascades (false discovery rate (FDR)<0.05). In vitro, cells derived from sorafenib-acquired resistant tumours and two sorafenib-resistant HCC cell lines were responsive to IGF or FGF inhibition. In vivo, FGF blockade delayed tumour growth and improved survival in sorafenib-resistant tumours. A sorafenib-resistance 175 gene signature was characterised by enrichment of progenitor cell features, aggressive tumorous traits and predicted poor survival in two cohorts (n=442 patients with HCC).ConclusionsAcquired resistance to sorafenib is driven by T-ICs with enrichment of progenitor markers and activation of IGF and FGF signalling. Inhibition of these pathways would benefit a subset of patients after sorafenib progression.

scholarly journals AXL Knock-Out in SNU475 Hepatocellular Carcinoma Cells Provides Evidence for Lethal Effect Associated with G2 Arrest and Polyploidization

2021 ◽  
Vol 22 (24) ◽  
pp. 13247
Author(s):  
Tugce Batur ◽  
Ayse Argundogan ◽  
Umur Keles ◽  
Zeynep Mutlu ◽  
Hani Alotaibi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Migration And Invasion ◽  
Advanced Hepatocellular Carcinoma ◽  
G2 Arrest ◽  
Knock Out ◽  
Acquired Drug Resistance ◽  
Phenotypic Changes ◽  
Hcc Cells

AXL, a member of the TAM family, is a promising therapeutic target due to its elevated expression in advanced hepatocellular carcinoma (HCC), particularly in association with acquired drug resistance. Previously, RNA interference was used to study its role in cancer, and several phenotypic changes, including attenuated cell proliferation and decreased migration and invasion, have been reported. The mechanism of action of AXL in HCC is elusive. We first studied the AXL expression in HCC cell lines by real-time PCR and western blot and showed its stringent association with a mesenchymal phenotype. We then explored the role of AXL in mesenchymal SNU475 cells by CRISPR-Cas9 mediated gene knock-out. AXL-depleted HCC cells displayed drastic phenotypic changes, including increased DNA damage response, prolongation of doubling time, G2 arrest, and polyploidization in vitro and loss of tumorigenicity in vivo. Pharmacological inhibition of AXL by R428 recapitulated G2 arrest and polyploidy phenotype. These observations strongly suggest that acute loss of AXL in some mesenchymal HCC cells is lethal and points out that its inhibition may represent a druggable vulnerability in AXL-high HCC patients.

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