Abstract

BackgroundHepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae.Methods Elytranthe parasitica (L.) Danser, a climbing parasitic shrub was investigated for its cytotoxic activity against HepG2, a hepatocellular carcinoma cell line by Sulforhodamine B (SRB) assay. Further, pro-oxidant activity of EP extract/fractions was studied using copper phenanthroline assay. To understand the mechanism of cell death, the pro-apoptotic effects of Hep-G2 cells treated with EP extract/fractions were visualized by dual staining using acridine orange and ethidium bromide, a morphological marker of apoptosis. Phytochemical profiling of EP was explored by estimating the phenol, flavonoid and tannin content in its various fractions and extract. The occurrence of gallic acid, a principal polyphenol in EP extract and fractions was detected and further quantified using HPTLC (High Performance Thin Layer Chromatography) fingerprinting.ResultActive fraction of Elytranthe parasitica, EP.DEE exhibited potent cytotoxic activity in a dose dependent manner against HepG2 hepatocellular carcinoma cell line with an IC50 of 56.7 ± 7.8 μg/mL. Dual staining with acridine orange and ethidium bromide revealed that HepG2 cells treated with EP active fractions underwent cell death chiefly by apoptosis. Highest phenol, flavonoid and tannin content were observed in active fractions, EP.EA (Ethyl acetate fraction) and EP.DEE (Diethyl ether fraction). Gallic acid was identified and quantified in EP extract and active fractions, EP.DEE and EP.EA.ConclusionOur findings indicate EP active fraction could be a promising contender in the treatment of hepatocellular carcinoma.

Highlights

  • Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide

  • Our findings indicate Elytranthe parasitica (L.) Danser (EP) active fraction could be a promising contender in the treatment of hepatocellular carcinoma

  • Effects of EP extract/fraction on HepG2 and Vero cells EP extract/fractions were tested against HepG2 hepatocellular carcinoma cell line and Vero cells using Sulforhodamine B (SRB) assay

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Summary

Introduction

Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. With approximately five lakh new cases being diagnosed every year, HCC has become the fifth most common cause of cancer worldwide [3]. In India, death due to HCC has been on a rise in the recent years with a mortality rate of 6.8 per 100, 000 in men and 5.1 per 100,000 in women [4]. Patients diagnosed with HCC have very low survival rate, with merely 17.2 % of them surviving for 5 years or more after diagnosis [5]. Common treatment strategies for HCC include hepatectomy, liver transplantation, radiofrequency ablation (RFA), radiotherapy and chemotherapy [6]. Medicinal plants and natural products, which have considerable chemotherapeutic value and comparatively fewer side effects [8,9,10], are increasingly being studied for treating cancer

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