Inhibitory potential of Tetrahydroxyflavanone in treating Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) belongs to a major and predominant primary liver cancer and it initiates in hepatocytes. It is the fifth most common cancer and is among the leading cause for cancer mortalities worldwide. HCC is the major histological subtype worldwide, comprising of 70% to 85% of the total liver cancer cases. Despite many therapeutic approaches and chemotherapy, it is still one of the most aggressive cancers and have high metastatic potential. These attributes render the liver cancer poor in prognosis. In most of the cases of HCC, patients are only diagnosed at advanced stages of cancer and only curative option left for them is either liver transplantation or tissue resection. The potential health benefits of tetrahydroxy flavonoids in alleviation and treatment of inflammation, cardiovascular diseases and cancer makes them an attractive and useful pharmacological agent. This study is designed to evaluate anti-proliferative and pro-apoptotic potential of Tetrahydroxyflavanone- a major flavonoid against hepatocellular carcinoma. HepG2 and Huh-7 cell lines were used to investigate the cytotoxic potential of tetrahydroxyflavanone on liver cancer cells. PKC delta belongs to the protein family Protein Kinase C and it has been reported to be involved in HCC progression. The study involves the assessment of the binding of Tetrahydroxyflavanone with target protein molecules PKC delta and KLF2; involved in the growth and proliferation of cancer cells through molecular docking approach. Cell viability assay, migration assay and colony formation assay were performed to investigate the anti-proliferative and pro-apoptotic effects of the drug on cancer cells. Apoptotic Annexin V/PI assay was performed by flow cytometry to quantify the number of early apoptotic cells, late apoptotic cells and dead cells after drug treatment. This study suggests that tetrahydroxyflavanone effectively has anti-proliferative and apoptotic properties where it reduces and inhibits the proliferation of cancer cells and induces apoptosis. Results from Flow cytometric analysis indicated that tetrahydroxyflavanone induces apoptosis in cancer cells and more than 70% of the cancerous cells underwent late apoptosis. Thus, our study suggests that tetrahydroxyflavanone can serve as an effective therapeutic and chemo preventive agent in the treatment of hepatocellular carcinoma.