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Title:
The effect of Telomerase inhibition on Alpha-Fetoprotein expression in Hepatocellular Carcinoma Cell line
Authors: Neama Elsayed Abd El-maksoud , Amr Ahmed Hassan, Walaa Bayoumie El-Gazzar , Heba Mohamed Abd El-Kareem, Shaymaa Mohamed Abd EL Rahman
Year: 2017
Keywords: Not Available
Journal: Not Available
Volume: Not Available
Issue: Not Available
Pages: Not Available
Publisher: Not Available
Local/International: International
Paper Link: Not Available
Full paper nama el sayed abdelmaksoud_09 ok.docx
Supplementary materials Not Available
Abstract:

Hepatocellular carcinoma is a very serious disease that can result in major number of deaths all over the world. Best surveillance especially to high risk individuals leads to best diagnosis of HCC and early management. There are two therapeutic strategies one with curative intent and another with palliative intent. Therapeutic strategy with curative intent includes Surgical resection- Liver transplantation- Locoregional ablation- Radiofrequency ablation (RFA)- Microwave ablation (MWA)- Cryoablation- Percutaneous ethanol injection (PEI), but therapeutic strategy with palliative intent includes Systemic therapy: sorafenib- External beam radiotherapy- Catheter-directed locoregional therapies- Transarterial embolization (TAE) - Transarterial hemoembolization (TACE) - Selective internal radiation therapy (SIRT, using Yttrium-90 microspheres) - Best supportive care, Palliative care,Hospice. Hepatocellular carcinoma (HCC) is considered a special challenge for doctors and patients because there is no certain curative treatment. In addition, the present treatment strategies have many disadvantages. To get a proper management for HCC; we should consider both present guidelines and individual patient. Furthermore, quality of patient life should be considered in treatment strategies. Various molecular pathways have been elucidated that they have a great role in HCC development and progression. By the help of these molecular pathways, drugs based on gene expression studies could be applied as a therapeutic modality which may slow down, stop or reverse the progression of HCC Telomeres are the non-coding ends of eukaryotic chromosomes and have an important role in the preservation and replication of the genome. Eukaryotic chromosomes are linear and that leads to shortening of telomere by the time, named as the “end-replication problem”, this problem occurs when telomere shortening became critical that results in growth arrest state, at that moment DNA damage signaling and cellular senescence is stimulated. Telomerase is a large ribonucleoprotein compound necessary for building telomeric DNA repeats (TTAGGG) at the 3′ ends of eukaryotic chromosomes, thus compensating the loss of DNA from each cycle of replication, thereby it solves replication problem and prohibit cell death. Cancer cells have the capability to replicate continuously that is due to the action of telomerase that maintains telomere length in most advanced tumors. Thereby, telomerase inhibitors which prevent the action of telomerase and prevent the capability of cancer cells to replicate can be used as specific anti¬cancer treatment. Costunolide is a sesquiterpene lactone separated from Michelia compressa. it has a wide range of biological activities, like anti-inflammatory, anti-virus, anti-cancer, anti-diabetes, anti-oxidant, anti-ulcer and anthelmintic activities. The anti-cancer activities of costunolide has recently been declared, involving the following possible mechanisms like inhibiting cancer cell proliferation, stimulating cancer cell differentiation, enhancing apoptosis, preventing metastasis and invasion, suppressing angiogenesis, reversing multidrug resistance. Costunolide inhibits telomerase by down-regulation of hTERT and transcriptional factors c-Myc and Sp1. The goal of our study is to examine the impact of telomerase inhibition on AFP mRNA expression in Hep G2 HCC cell line by using real time PCR technique. HepG2 cells were treated with costunolide concentrations (10, 50, 100 μM), then AFP mRNA expression is investigated by RT PCR for these three different concentrations after 48hs and 96hs. Results of the reverse transcription- PCR analysis of AFP mRNA in HepG2 cells after treatment with costunolide (10, 50 and 100μM) for 48hs and measuring FLD of AFP for each concentration revealed that Costunolide 10μM decreased the AFP gene expression by 0.593 fold as compared to control and Costunolide 50, 100 μM significantly decreased the AFP gene expression by 0.375, 0.266 fold respectively as compared to control. Also the expression levels of the alpha fetoprotein gene of these 3 costunolide concentrations after 96hs has significantly decreased by 0.259, 0.167, and 0.083 fold respectively, as compared to control.

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