Vol. 7, Issue 11 (2018)

Author(s):
Asish Bhaumik, Dr. M Chinna Eswaraiah and Dr. Raja Chakraborty

Abstract:
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults, and is the most common cause of death in people with cirrhosis. It occurs in the setting of chronic liver inflammation, and is most closely linked to chronic viral hepatitis infection (hepatitis B or C) or exposure to toxins such as alcohol or aflatoxin. Certain diseases, such as haemochromatosis and alpha 1-antitrypsin deficiency, markedly increase the risk of developing HCC. Metabolic syndrome and NASH are also increasingly recognized as risk factors for HCC. Non-alcoholic fatty liver disease (NAFLD) is a condition in which fat builds up in your liver. Non-alcoholic steatohepatitis (NASH) is a type of NAFLD. If you have NASH, you have inflammation and liver cell damage, along with fat in your liver. As with any cancer, the treatment and prognosis of HCC vary depending on the specifics of tumour histology, size, how far the cancer has spread, and overall health. The in vitro anticancer activity of synthesized compounds was carried out by SRB assay where as in vivo anticancer activity of synthesized compounds was carried out against DEN and CCl₄ induced hepatocellular carcinoma in rat model. In the present study it was displayed that all the synthesized compounds (AB1-AB8) had the potential ability to inhibit the proliferation of HEPG2 cancer cell with the highest percentage of growth inhibition 93.92%, 92.23%, 89.53%,91.56%, 92.91%, 89.22%, 93.59%, 91.22%, etc. at dose 300 µg/ml and IC₅₀ values of synthesized compounds were found to be 2.3 µg/ml, 3.1 µg/ml, 3.6 µg/ml, 3.4 µg/ml, 2.9 µg/ml, 3.9 µg/ml, 2.5 µg/ml, 3.8 µg/ml etc. and std. drug 5-FU (94.26%) found to be 2.2 µg/ml. The in vivo experimental data obtained from HCC in rat model displayed that all the synthesized compounds had the potential capability to restore normal hepatocellular status by inhibition of portal tract necrosis, centrilobular degeneration, fibrosis and anaplasia which was indicated by reduction in α-fetoprotein (AFP) by the synthesized compounds (AB1-AB8), a potential tumour marker raised in liver cancer and in addition it was also found that all the synthesized compounds restored the levels of SGOT, SGPT and ALP at the same dose. The apoptosis of the cancer cells caused by the synthesized compounds were also observed and it was indicated that compound AB1; AB7; AB5; AB2; and AB4 were able to significantly induce HEPG2 cells apoptosis among the eight synthesized compounds.