Screening and Evaluation of Various Plant Extracts as Anti – Cancer and Multidrug Resistance Reversal Agent

Abstract

The present study investigates the anti-cancer and multi drug resistance (MDR) reversal potential of hydroalcoholic Allium cepa, Allium sativum, Boerhavia diffusa and Eclipta alba extracts through in vitro as well as in vivo experiments. In vitro anti-cancer study was done with human carcinoma cell line (HepG2, A498 and C6) and for in vitro MDR study we established multidrug resistant HepG2 cell line (DR-HepG2), using 2-Acetylaminofluorene (2-AAF) and AflatoxinB1 (AFB1). Diethylnitrosamine (DEN) and AAF were used for liver cancer induction in rat model, whereas for MDR induction, AAF was used for in vivo experiments. In in vitro cancer study the hydroalcoholic extracts exerted antiproliferative effects on cell lines in a dose-dependent manner. The plant extracts (PE) were orally administered at the concentration of 250 and 500 mg/kg body weight in induced rat models. EAE inhibited the activity of matrix metalloproteinases (MMP2 and 9), preferentially MMP-9, at the doses of 20μg/ml in HepG2 and 500mg/kg in in vivo. PE were also able to induce apoptosis in both cell lines and cancer induced animals, promising result was given by EAE and ASE. The level of anti-oxidant enzymes was also studied in tissue and serum along with biochemical prameters. In cancer induced animal model significant increase in BrdU positive cells was observed, PE assisted in lowering proliferation. Cancer cells have higher levels of reactive oxygen species (ROS) than normal cells, and ROS are, in turn, responsible for the maintenance of the cancer phenotype. Treatment with PE, a decline in the reactive oxygen species (ROS) was observed revealing the ROS scavenging properties of the extracts. AFP levels were found to increase drastically in liver cancer induced animals confirming induction and progression of liver cancer, PE treatment was found to bring back the altered levels within normal range indicating the protective effect of plant extract over liver cancer induction. RT-PCR analysis revealed that the mRNA expression of NFƙB was markedly decreased in vitro and in vivo upon treated with the PE, preferably by EAE. In MDR study PE were found to have a significant reversal on MDR in DR-HepG2. Further, our results showed that EAE could significantly inhibit P-glycoprotein expression and mRNA transcription. Our data suggest the presence of bioactive compounds in PE, capable of augmenting liver carcinoma cells by lowering the level of MMP, ROS, induction of apoptosis, altered NFƙB signaling and reversing MDR but among all extracts EAE shown the superlative result. These results suggest that EAE is a novel anti-cancer and potent MDR reversal agent and may be a potential adjunctive agent for tumor chemotherapy.