Title: Molecular Investigation of Potential Chemotherapeutic activity of novel nanoformulation of nutraceuticals; In-Vivo and In-Vitro Study
Funder: The Academy of Medical Sciences

Abstract: Hepatocellular carcinoma (HCC) is the ultimate stage of the liver diseases from earlier hepatitis, fibrosis and cirrhosis[1]. Previous emerging data indicated that more than 80 % of patients of hepatic cancer were underlying liver cirrhosis[3]. HCC was ranked as third highest cause of cancer related death with annual mortalities; 745,500 and sixth most common cancer with 782,500 new cases every year worldwide during 2012[4]. Liver cancer incidence is significantly increased in the low-income areas or developing countries such as Northern and western African, Eastern and southeastern Asia, while is much lower in well-developed countries except southern Europe[5]. In addition, the incidence of HCC in male population has been rose in Austria, Denmark, Germany, Greece, Ireland, Portugal, Norway, Spain, Switzerland, and UK during the last ten years[5]. Chronic infections with hepatitis B and hepatitis C viruses are the main causes of HCC, while contamination of foodstuff with a group of mycotoxins produced such as aflatoxins, is an essential contributor to HCC burden in many low-income country[6]. Management of HCC including resection, liver transplantation (LT), percutaneous ablation, chemoembolization, systemic chemotherapeutic agents and vaccination techniques against HBV as well as antiviral drugs. Although, sorafenib could successfully increase the overall survival of the treated patients, there are still several limitations to its use, due to acquired resistance Thus, enormous agents and novel drug delivery systems are still under investigations with promising outcomes for treatment of HCC. Previous studies suggested that nutraceuticals might play a role in protection against HCC due to their potential antiproliferative activity. Thus, the current study aims to investigate the potential anticancer effects of nanoformulations of selected nutraceuticals; diosgenin, myricetin and baicali on hepatoma cell line Hep G2 and Hep 3B, Huh 7. In order to evaluate the cytotoxic activity on the cell proliferation on hepatoma cell lines, MTT assay will be performed. Effects of different treatment on the induction of cell death will be investigated by nuclear condensation assay. An FITC annexin-V Apoptosis Detection Kit I will be used to determine cell number within different stages of cell death. In order to evaluate the potential impact of the nanoformulation of nutraceutical on the molecular pathway that drive chemotherapeutic drug resistance in HCC, western blotting will be performed to assess the expression of PI3K, AKT/ phosphorylated P-AKT and ERK 1.2/ P-ERK 1.2 on hepatoma cell lines. 1.Levy, A.D., Malignant liver tumors. Clinics in liver disease, 2002. 6(1): p. 147-164. 2.Fattovich, G., et al., Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology, 2004. 127(5): p. S35-S50. 3.Torre, L.A., et al., Global cancer statistics, 2012. CA: a cancer journal for clinicians, 2015. 65(2): p. 87-108. 4.Kew, M.C. and M. Kew, Hepatocellular carcinoma: epidemiology and risk factors. J Hepatocellular Carcinoma, 2014. 1: p. 115-125. 5.Liver, E.A.F.T.S.O.T., EASL–EORTC clinical practice guidelines: management of hepatocellular carcinoma. Journal of Hepatology, 2012. 56(4): p. 908-943. 6.Hamzawy, M.A., et al., Dietary supplementation of Calendula officinalis counteracts the oxidative stress and liver damage resulted from aflatoxin. ISRN nutrition, 2013. 2013.


Research activity codes: 5.1 PHARMACEUTICALS;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CANCER AND NEOPLASMS