Browsing by Subject "growth inhibition"

Now showing 1 - 3 of 3

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
Differential p21 expression after ionizing and UVC radiation in EBV-transformed lymphoblastoid cells
(2000) Moyret-Lalle, C.; Lalle P.; Pedeux, R.; Guillot, C.; Martel, S.; Magaud J.-P.; Puisieux, A.; Ozturk, M.
Responses to DNA-damaging agents appear to be coordinated by p53 through transcriptional activation of critical target genes. Among them, p21WAF1 encodes a protein preventing cells from entering S phase. It is not clear whether p53-mediated response varies depending on the type of DNA damage. Here, we have decided to compare the p53-mediated response of EBV-transformed lymphoblasts to ionizing radiation and UVC irradiation. We have shown that these cells respond to ionizing radiation by a cell cycle arrest as expected. Surprisingly they failed to do so after UVC treatment. Accordingly there was no significant induction of p21 protein in UVC exposed cells despite p53 accumulation. Using isogenic EBV-transformed lymphoblastoid cells expressing E6 protein of HPV18, we have demonstrated that there was no evidence of p53-dependent cell cycle arrest after UVC irradiation. These observations suggest that the p53-mediated response to UVC, in contrast to ionizing radiation, was compromised in EBV-transformed cells and might be cell type-dependent.
Open Access
MST1 is a multifunctional caspase-independent inhibitor of androgenic signaling
(2011) Cinar, B.; Collak F.K.; Lopez, D.; Akgul, S.; Mukhopadhyay, N.K.; Kilicarslan, M.; Gioeli, D.G.; Freeman, M.R.
The MST1 serine - threonine kinase, a component of the RASSF1-LATS tumor suppressor network, is involved in cell proliferation and apoptosis and has been implicated in cancer. However, the physiologic role of MST1 in prostate cancer (PCa) is not well understood. Here, we investigated the possibility of a biochemical and functional link between androgen receptor (AR) and MST1 signaling. We showed that MST1 forms a protein complex with AR and antagonizes AR transcriptional activity as shown by coimmunoprecipitation (co-IP), promoter reporter analysis, and molecular genetic methods. In vitro kinase and site-specific mutagenesis approaches indicate that MST1 is a potent AR kinase; however, the kinase activity of MST1 and its proapoptotic functions were shown not to be involved in inhibition of AR. MST1 was also found in AR - chromatin complexes, and enforced expression of MST1 reduced the binding of AR to a well-characterized, androgen-responsive region within the prostate-specific antigen promoter. MST1 suppressed PCa cell growth in vitro and tumor growth in mice. Because MST1 is also involved in regulating the AKT1 pathway, this kinase may be an important new link between androgenic and growth factor signaling and a novel therapeutic target in PCa. ©2011 AACR.