Browsing by Subject "hepatocellular carcinoma"

Now showing 1 - 5 of 5

Open Access
Anti-cancer and anti-hepatitis C virus NS5B polymerase activity of etodolac 1,2,4-triazoles
(Taylor and Francis Ltd, 2015) Çikla-Süzgün P.; Kaushik-Basu, N.; Basu, A.; Arora P.; Talele, T.T.; Durmaz I.; Çetin-Atalay, R.; Küçükgüzel, S.G.
Arachidonic acid is an unsaturated fatty acid liberated from phospholipids of cell membranes. NSAIDs are known as targets of cyclooxygenase enzyme (COX-1, COX-2 and COX-3) in arachidonic acid metabolism. This mechanism of COX-2 in carcinogenesis causes cancer. In addition, COX-2 plays a role in the early stages of hepatocarcinogenesis. Hepatitis C virus (HCV) infection is cause of liver cirrhosis and hepatocellular carcinoma (HCC). The aim of our study was to improve effective agents against HCV. A novel series of new etodolac 1,2,4-triazoles derivatives (4a-h) have been synthesized and investigated for their activity against HCV NS5B polymerase. Compound 4a was found to be the most active with IC50 value of 14.8 M. In accordance with these results, compound 4a was screened for anti-cancer activity on liver cancer cell lines (Huh7, Mahlavu, HepG2, FOCUS). Compound 4a showed anti-cancer activity against Huh7 human hepatoma cell line with IC50 value of 4.29 M. Therefore, compound 4a could be considered as a new anti-cancer and anti-HCV lead compound. © 2015 Informa UK Ltd.
Open Access
Characterization of cancer stem cells in hepatocellular carcinoma
(2014) Abdüsselamoğlu, Merve Deniz
Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer worldwide due to the challenges in both its diagnosis and treatment. According to recent studies, HCC tumors, like many other solid tumors are initiated and maintained by a subpopulation of cells called “cancer stem cells (CSCs)” or "tumor-initiating cells (TICs)". HCC stem cells can be identified by the expression of cardinal CD markers such as CD133 (Prominin-1) and epithelial cell adhesion molecule (EpCAM). This study primarily focuses on the investigation of mechanisms involved in the generation of HCC stem cell sub-population using a panel of 15 HCC cell lines. Preliminary data indicates that four cell lines (27%) display CD133+ stem cell populations at frequencies ranging from 8 to 90% when tested by flow cytometry. Among these CD133 positive cell lines, two isogenic cell line with different positivity levels prompted us to focus on two specific cell lines;, i) parental HepG2 cell line and its clone, which was transfected with four copies of hepatitis B virus (HBV), namely ii) HepG2-2215. With tumorigenicity assay induced in atymic nude mice, data revealed that HepG2-2215 that had higher CD133+ ratio, showed higher and rapid tumor formation than parental HepG2 that had much lower CD133+ sub-cellular proportion. Microarray analyses were performed to underpin the mechanisms of in CD133+ cell number variations of these two cell lines. Our initial findings suggested that FGFR signaling pathway might have played a role. To investigate these findings, FGFR signaling pathway was inhibited via potent inhibitor as well as knock down with siRNA. However, preliminary data did not indicate these presumptions and further studies are needed to clarify the relationship between FGFR signaling and CSC formation in HCC. Also, role of suppressive oligodeoxynucleotide (ODN) was studied to see the effects of suppression of DNAdriven immunostimulation. Findings showed that suppressive ODN decreased CD133 levels, which indicates the difference between these two cell lines may arise from the HBV transfection of HepG2-2215 cell line which can produce HBV particles. However, further investigation is needed to understand the relationship between HBV infection and CSC population in HCC.
Open Access
In silico analysis of mutant p53(R249S) oncogenicity in hepatocellular carcinoma
(2007) Ovezmuradov, Guvanchmurad
Oncogenic properties of mutant p53 proteins still stand as an ill-known subject, and the mechanism responsible for this phenomenon remains to be uncovered. This thesis aims to uncover the effect of p53 codon R249S ((AGG→AGT, arginine to serine) mutation on the development of hepatocellular carcinoma (HCC) through high throughput transcriptomics analysis using oligonucleotide arrays. We compared the expression profiles of HepG2 cells carrying wt and mutant p53(R249S). Microarray data analysis revealed a molecular signature consisting of 84 differentially regulated genes, showing that the expression of mutant p53(R249S) in HepG2 cells resulted in a distinct expression profile. Furthermore, mapping these significant differentiallyexpressed genes to the p53 interaction network revealed a putative interaction network representing functional outcomes of p53(R249S) expression in the context of diverse molecular interactions. Our results clearly demonstrated that several Hepatocyte Nuclear Factors (HNF1A, HNF4A and HNF6) could play an essential role in mediating mutant p53 oncogenic activity in HCC, as the key molecules of the gene network.
Open Access
Mineralocorticoid and glucocorticoid receptors as novel targets in breast and liver cancer therapies
(2020-12) Güneş, Damla
Cell signaling is a complex phenomenon and is maintained through intertwined signal transmissions within and in-between the cells. Anti-cancer therapies are often challenged by this fact due to crosstalk-associated activation of alternative survival routes. Hence, development of new treatment strategies and identification of novel prognostic markers depends on in-depth knowledge on cell signaling routes altered in cancer and possible crosstalk paths. Herein, mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) signaling, two closely related members of steroid receptor hormone family, and their possible crosstalk were studied across breast and liver cancer cell lines. In breast cancer cell lines, estrogen responsive and MR expressing T47D was used in order to study possible crosstalk among Estrogen receptor (ER) and MR. MR-GR ligand aldosterone (ALDO) and ER ligand estrogen (E2) administered to breast cancer cells alone and in combination and, MR, ER and GR and their downstream signaling members were studied employing qRT-PCR and Western blot assays. Furthermore, ALDO, E2, ALDO-E2 hormone administrations were also used for cell viability assessments. Our results implied possible interactions of ALDO-E2 signaling at the level of cell viability, and at mRNA levels of progesterone receptor. In liver cancer cell lines, MR and GR was investigated as targets of a novel treatment. Liver cancer subtype hepatocellular carcinoma (HCC) has high mortality rate with limited treatment options. Multi-kinase inhibitor Sorafenib (SFB) with mild effectivity is most known systemic therapy against HCC. To potentiate the effectiveness of SFB and overcome to the crosstalk associated limitations, combinatorial drug treatment approach targeting multiple signaling modalities has been adopted in literature. Previously in our lab, SFB was combined with repurposed anti-psychotic drug TFP as a novel combinatorial treatment against hepatocellular carcinoma (HCC) and liver cancer cell lines. Cellular viability was synergistically reduced by SFB-TFP in HCC cell line Hep3B, while antagonistic effects on viability in SkHep1 was apparent. Herein, two liver cancer cell lines Hep3B and SkHep1, were used in comparison to unravel mechanism of action of SFB-TFP combination at the protein level. Apoptosis, cell cycle, PI3K/AKT/mTOR and MAPK pathways were investigated in addition to MR and GR. Our results revealed several markers indicating success of drug combinations and targeted pathways at protein level which needs to be pursued further.
Open Access
Role of JMJD5 in liver cancer
(2013) Demirdizen, Engin
Being one of the most common cancer types in human population, hepatocellular carcinoma (HCC) has high rate of deaths due to the challenges in its diagnosis and treatment. In recent years, epigenetic regulators have come into play in HCC research to overcome with those challenges. As potential drug targets, histone demethylases has drawn a lot of interest. In this respect, several studies have focused on a specific member of this family, JMJD5, suggesting its possible function in tumor suppression, while the opposite argument has also been proposed by several reports. Preceding studies on JMJD5 in our lab also pointed to a possible tumor suppressor function. Hence, this study aimed to elucidate the role of JMJD5 in liver cancer development using SNU449 HCC cell line stably expressing JMJD5. For this purpose, stable clones overexpressing wild-type and mutant JMJD5 as well as controls were generated. A comparative analysis of these clones was performed. No definite results could be obtained for the effect of JMJD5 on cell proliferation, but the number of cells in G1 declined, whereas that in G2/M inclined in clones expressing wild-type and mutant JMJD5, suggesting that JMJD5 affects cell cycle progression. In addition, cell motility was decreased, while anchorage-independent colony formation ability was enhanced in both mutant and wild type JMJD5- expressing clones. Decrease in cell motility is considered to be anti-tumoral, whereas anchorage-independent growth is a malignant change. Our findings suggest that JMJD5 may have a quite complex role in liver tumorigenesis. Further in vivo studies may help to clarify some of these apparently conflicting in vitro effects.