scholarly journals Potential Role of CD133 Expression in the Susceptibility of Human Liver Cancer Stem-Like Cells to TRAIL

2016 ◽  
Vol 24 (6) ◽  
pp. 495-509 ◽  
Author(s):  
Su-Hoon Lee ◽  
Suh-Kyung Hyun ◽  
Hak-Bong Kim ◽  
Chi-Dug Kang ◽  
Sun-Hee Kim
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Human Liver ◽  
Surface Expression ◽  
Small Population ◽  
Cell Surface Expression ◽  
High Recurrence Rate ◽  
Cd133 Expression ◽  
New Strategy ◽  
Human Liver Cancer

Hepatocellular carcinoma (HCC) is one of the most common malignancies, with a poor prognosis and high recurrence rate. In the present study, we identified CD133, one of the markers of cancer stem cells, as a novel molecular target of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In four human HCC cell lines established from primary HCC tumors, we found that CD133-high human liver cancer stem-like cells (CD133hi) derived from the SNU-475 cell line were highly susceptible to TRAIL compared to other HCC cell lines with a small population of CD133. CD133hi SNU-475 cells showed upregulation of TRAIL receptor DR5 and stemness-related genes such as c-Myc and ABC transporters compared to their CD133-low (CD133lo) cells. Hypersensitivity of CD133hi cells to TRAIL was associated with c-Myc-mediated upregulation of DR5 and downregulation of c-FLIPL in the cells. Knockdown of CD133 expression in CD133hi cells resulted in the downregulation of c-Myc, and depletion of c-Myc caused a decrease in the cell surface expression of DR5 and an increase in the expression of c-FLIPL and, consequently, attenuated TRAIL-induced cytotoxicity and apoptosis of CD133hi cells. These results suggest that TRAIL may provide a new strategy for CD133hi CSCs of HCC-targeted therapies and, potentially, for therapies of other CD133-expressing types of cancer.

scholarly journals ImmunoPET as Stoichiometric Sensor for Glypican-3 in Models of Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Olivia J. Kelada ◽  
Nicholas T. Gutsche ◽  
Meghan Bell ◽  
Rose M. Berman ◽  
Kwamena E. Baidoo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
Liver Cancer ◽  
Cell Lines ◽  
Human Liver ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Human Liver Cancer ◽  
Gpc3 Expression

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. While conventional imaging approaches like ultrasound, CT, and MRI play critical roles in the diagnosis and surveillance of HCC, improved methods for detection and assessment of treatment response are needed. One promising approach is the use of radiolabeled antibodies for positron emission tomography (immunoPET) imaging. Glypican-3 (GPC3) is a proteoglycan that is highly expressed in the majority of HCC tumors. GPC3-specific antibodies are used to diagnose HCC histopathologically, and have been proposed as a treatment of HCC. Here, we design, synthesize and demonstrate that our humanized immunoPET agent, [89Zr]Zr-DFO-TAB-H14, can stoichiometrically bind to models of human liver cancer with varied GPC3 expression. Methods: The GPC3-specific monoclonal humanized IgG1, TAB-H14, was used as a scaffold for engineering our immunoPET agent. Fluorescent and deferroxamine (DFO) chelate conjugates of TAB-H14 were characterized using mass spectrometry. Binding affinity of TAB-H14 and conjugates for GPC3 was determined in cell-free biolayer interferometry, and cell-based radioimmunoassays. GPC3-expression was assessed by flow cytometry and immunofluorescence using commercially available anti-GPC3 antibodies and TAB-H14 in GPC3−(A431) and GPC3+ cell lines including an engineered line (A431-GPC3+, G1) and liver cancer lines (HepG2, Hep3B, and Huh7). DFO-TAB-H14, was radiolabeled with Zr-89. Mice were subcutaneously engrafted with the aforementioned cell lines and in vivo target engagement of the immunoPET agent [89Zr]Zr-DFO-TAB-H14 was determined using PET/CT, quantitative biodistribution, and autoradiography. Results: TAB-H14 demonstrated subnanomolar to nanomolar affinity for human GPC3. Fluorescently tagged TAB-H14 was able to bind to GPC3 on cell membranes of GPC3-expressing lines by flow cytometry. These results were confirmed by immunofluorescence staining of A431, G1 HepG2, Hep3B, and Huh7 tumor sections. ImmunoPET imaging with [89Zr]Zr-DFO-TAB-H14 showed stoichiometric tumor uptake corresponding to the cell surface expression levels. Autoradiography and immunostaining confirmed in vivo findings. Conclusion: We systematically demonstrate that the humanized immnoPET agent [89Zr]Zr-DFO-TAB-H14 specifically and stoichiometrically binds to GPC3 in several models of human liver cancer, serving as a promising in vivo GPC3 sensor. This agent may provide utility in HCC diagnosis and surveillance, and the selection of candidates for GPC3-directed therapies.

scholarly journals Antiproliferative Effect of Lenvatinib on Human Liver Cancer Cell Lines In Vitro and In Vivo

2019 ◽  
Vol 39 (11) ◽  
pp. 5973-5982 ◽  
Author(s):  
SACHIKO OGASAWARA ◽  
YUTARO MIHARA ◽  
REIICHIRO KONDO ◽  
HIRONORI KUSANO ◽  
JUN AKIBA ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Liver ◽  
Antiproliferative Effect ◽  
Liver Cancer Cell ◽  
Human Liver Cancer Cell ◽  
Human Liver Cancer

scholarly journals A Titanium (IV)–Dithiophenolate Complex and Its Chitosan Nanocomposite: Their Roles towards Rat Liver Injuries In Vivo and against Human Liver Cancer Cell Lines

2021 ◽  
Vol 22 (20) ◽  
pp. 11219
Author(s):  
Nadia Z. Shaban ◽  
Salah A. Yehia ◽  
Doaa Awad ◽  
Shaban Y. Shaban ◽  
Samar R. Saleh
Keyword(s):  
Oxidative Stress ◽  
Liver Cancer ◽  
Cell Lines ◽  
Rat Liver ◽  
Liver Damage ◽  
Human Liver ◽  
Therapeutic Effects ◽  
Liver Injuries ◽  
Human Liver Cancer

Titanium (IV)–dithiophenolate complex chitosan nanocomposites (DBT–CSNPs) are featured by their antibacterial activities, cytotoxicity, and capacity to bind with DNA helixes. In this study, their therapeutic effects against rat liver damage induced by carbon tetrachloride (CCl4) and their anti-proliferative activity against human liver cancer (HepG2) cell lines were determined. Results of treatment were compared with cisplatin treatment. Markers of apoptosis, oxidative stress, liver functions, and liver histopathology were determined. The results showed that DBT–CSNPs and DBT treatments abolished liver damage induced by CCl4 and improved liver architecture and functions. DNA fragmentation, Bax, and caspase-8 were reduced, but Bcl-2 and the Bcl-2/Bax ratios were increased. However, there was a non-significant change in the oxidative stress markers. DBT–CSNPs and DBT inhibited the proliferation of HepG2 cells by arresting cells in the G2/M phase and inducing cell death. DBT–CSNPs were more efficient than DBT. Low doses of DBT and DBT–CSNPs applied to healthy rats for 14 days had no adverse effect. DBT and DBT–CSNP treatment gave preferable results than the treatment with cisplatin. In conclusion, DBT–CSNPs and DBT have anti-apoptotic activities against liver injuries and have anti-neoplastic impacts. DBT–CSNPs are more efficient. Both compounds can be used in pharmacological fields.

scholarly journals Mechanism of action of novel piperazine containing compound toxicant against human liver cancer cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1588 ◽  
Author(s):  
Nima Samie ◽  
Sekaran Muniandy ◽  
MS Kanthimathi ◽  
Batoul Sadat Haerian
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Liver ◽  
Cancer Cell Lines ◽  
Liver Cancer Cell ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

The purpose of this study was to assess the cytotoxic potential of a novel piperazine derivative (PCC) against human liver cancer cells. SNU-475 and 423 human liver cancer cell lines were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on liver cancer cells with an IC50 value of 6.98 ± 0.11 µM and 7.76 ± 0.45 µM against SNU-475 and SNU-423 respectively after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-κB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. Results of this study suggest that PCC is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.

scholarly journals HNF1α inhibition triggers epithelial-mesenchymal transition in human liver cancer cell lines

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Pelletier ◽  
Sandra Rebouissou ◽  
Danijela Vignjevic ◽  
Paulette Bioulac-Sage ◽  
Jessica Zucman-Rossi
Keyword(s):  
Liver Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Liver ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Lines ◽  
Liver Cancer Cell ◽  
Mesenchymal Transition ◽  
Human Liver Cancer Cell ◽  
Human Liver Cancer
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