Browsing by Author "Shebl, Rania I"

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    THE BACILLUS CALMETTE-GUéRIN DERIVED PURIFIED PROTEIN (PPD) POTENTIATES IN-VITRO ANTI-CANCER ACTIVITY OF CERASTES CERASTES SNAKE VENOM IN COLON AND PROSTATE CANCER CELLS
    (Inventi, 2017-06) Sabatier, Jean-Marc; Shebl, Rania I; Bakkar, Ashraf; Mohamed, Aly Fahmy; Ayman, Mohamed
    Prostate and colon cancer represent a major health problem worldwide. In the present study, we evaluated the anticancer properties and cytotoxicity of Cerastes-cerastes (CC) snake venom on colon (Caco-2) and prostate (PC-3) cancer cells after their pretreatment with variable concentrations of Bacillus Calmette-Guérin (BCG) derived purified protein derivative (PPD). We monitoned the cell cycle arrest profile and specific cellular apoptosis markers (i.e. pro- and anti-apoptotic genes P53, Bax and Bcl-2 in CC- and BCG/PPD-pretreated cells using real time PCR. The cytotoxicity was determined by using MTT assay. Our data show that 24 h-treatment of cancer cells with CC venom induced a concentration-dependent cytotoxicity with IC50 values of 60 (Caco-2 cells) and 81 (PC-3 cells) μg/ml. Interestingly, addition of BCG/PPD at 25 and 50 μg/ml markedly increased the CC venom-induced toxicity on cancer cells, with IC50 values of 1.04 and 0.59 μg/ml for Caco-2 (up to 102-fold increase) or 2.78 and 0.70 μg/ml for PC-3 cells (up to 116-fold increase). By analyzing the cell cycle arrest and related gene expression pattern, the main phase of cell cycle arrest was found to be G2/M in both cell lines. An S-phase arrest was also observed in PPD pretreated colon Caco-2 cell line to a greater extent than that observed in cells only treated with CC venom. Up regulation of proapoptotic and down regulation of anti-apoptotic genes in PPD pretreated cells were significantly enhanced as compared to cells treated with CC venom alone. In this study, we suggest that PPD -via its synergistic action with the CC venom-might be used as an enhancer of the anti-cancer properties of CC venom.
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    ZINC OXIDE NANORODS INDUCED APOPTOSIS IN HUMAN PROSTATIC AND HEPATOCELLULAR CARCINOMA VIA MITOCHONDRIA DYSFUNCTION MEDIATED THOUGH BAX/ BCL-2 WITH P53 ACTIVATION
    (Inventi, 2017-06) Sabatier, Jean–Marc; Bakkar, Ashraf; Shebl, Rania I; Mohamed, Aly Fahmy; Hassan, Amr; Gamal, Omar
    The present study aimed to experimentally synthesis zinc oxide nanorods (ZnO NRs) using albumin as bio-template by a sol-gel method and to characterize the products using UV-Visible, FTIR, XRD, TGA and HRTEM. The crystallinity and morphology of the ZnO NRs were confirmed to have an average diameter of 70 nm and 250 nm length. The formation mechanism depends on the nucleation of Zn+2 in sites of the albumin followed by Zn+2 assembly in the cavity of albumin and finally thermal treatment to form ZnO in rod shape then calcination to final form ZnO NRs form as shown in HRTEM. Cytotoxicity of developed ZnO-NRs was conducted using MTT assay on both HepG2 and PC-3 cells. Data revealed that ZnO-NPs were toxic to both HepG2 and PC-3 cell lines displayed a concentration dependent viability. The flow cytometry illustrated that apoptosis of hepatocellular carcinoma (HepG2) depends on the cell growth arrest at G1/S phase indicated that inhibition Cyclin E (CDK 2) while prostatic carcinoma (PC-3) depends cell growth arrest at G2/M phase indicated that inhibition of Cyclin ACDK1. The apoptotic mechanism was investigated using rt-PCR. The apoptotic mechanism in both cell lines HepG2 and PC-3 was depended on the upregulated of Bax protein and down regulation of Bcl-2 indicated that the mechanism of mitochondrial outer membrane permeability (MOMP) or mitochondria dysfunction was dependent on activation of P53 protein.