ACCEPTED LECTURE

Abstract:
Although the chemosensitizing effect of Dexamethasone (DEX) was previously reported, this study aimed to explore how far cotreatment of breast cancer cells with paclitaxel (PTX) and DEX mimics the anticancer effect of nanoformulated PTX. To establish this goal, PTX was nanoformulated with PLGA and physically authenticated. Breast cancer cells (MCF-7) were treated with PTX or PTX-NPs in presence or absence of low concentration (10 nM) of DEX. Cells viability, apoptosis and the expression of PTX resistance gene (TRX1) and PTX metabolizing genes (CYP2C8 and CYP3A4) were investigated. The nanoformulated PTX was validated by nano-size assessment, increased the anionic surface charge and prober conjugation with the biodegradable carrier (PLGA), as indicated by the FTIR spectroscopy. Initially, the IC50 value of PTX was 19.3 μg/ml and cotreatment with DEX minimized it to 5.22 μg/ml, whereas PTX-NPs alone inhibited cell proliferation with IC50 6.67 μg/ml. Also, in presence of DEX, PTX-NPs further decreased the IC50 to5 μg/ml. In parallel, DEX has increased the cell responsiveness to PTX without potentiating its apoptotic effect. Moreover, the glucocorticoid (with PTX or PTX-NPs) downregulated TXR1 gene by 26% (P<0.01) and 28.4% (P < 0.05), respectively. Similarly, the mRNA level of CYP3A4 significantly decreased in presence of DEX. The main PTX metabolizing gene CYP2C8, in contrast, was upregulated, especially in cells cotreated with PTX/DEX (P<0.001). Conclusively, the study reports that cotreatment of breast cancer cells with submolar concentration of DEX acts as similar as the nanoformulated PTX, possibly through its modulatory effects on the expression of the main PTX metabolizing gene (CYP2C8) and downregulating Taxol resistance gene. Biography
Professor Hessien received his B.S., M.Sc. in biochemistry from Ain-Shams University, Egypt and his Ph.D. from Ain-Shams and Albert Einstein College of Medicine, NY, USA (channel program) in Molecular Biology of hepatitis B virus in 2000. After receiving his degree, he was awarded Fulbright fellowship to Lombardi Cancer Center, Georgetown University, Washington, D.C. with Professor Richard Pestell in 2003. In his leave to KSA he was the head of The Department of Medical Laboratory Technology in the International Academy of Health Sciences and Community College, KKU. Also, he was an associate professor of Medical Biochemistry in the Collage of Medicine, KKU. Now he is a full professor in the Division of Biochemistry, faculty of Science Tanta University, Egypt, where he established his lab and crew members working on cancer cell biology. Prof Hessien published more than 40 research articles, 5 books and received many grants.