Comparision of the Cytotoxic Effects of Birch Bark Extract, Betulin and Betulinic Acid Towards Human Gastric Carcinoma and Pancreatic Carcinoma Drug-sensitive and Drug-Resistant Cell Lines

Marcin Drag,Manfred Dietel,Pawel Surowiak,Józef Oleksyszyn,Malgorzata Drag-Zalesinska,Hermann Lage

doi:10.3390/molecules14041639

Abstract

Betulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicity towards a number of cancer cell lines. These compounds can be found in the bark of the many plants. In this report we have compared the cytotoxic activity of crude birch bark extract and purified betulin and betulinic acid towards human gastric carcinoma (EPG85-257) and human pancreatic carcinoma (EPP85-181) drug-sensitive and drug-resistant (daunorubicin and mitoxantrone) cell lines. Our results show significant differences in sensitivity between cell lines depending on the compound used, and suggest that both betulin and betulinic acid can be considered as a promising leads in the treatment of cancer.

Highlights

Chemotherapy is a standard treatment for advanced neoplastic diseases, following surgical removal of tumors
The aim of this work was to compare the cytotoxicity of a crude extract of birch bark, pure betulin, and betulinic acid toward drug-sensitive and drug-resistant human gastric carcinoma (EPG85-257) and human pancreatic carcinoma (EPP85-181) cell lines
We used a procedure employing ethanol as solvent for the isolation of the betulin and betulinic acid from birch bark, since this method allows for almost complete isolation of both terpenes from solid phases

Summary

Introduction

Chemotherapy is a standard treatment for advanced neoplastic diseases, following surgical removal of tumors. Considering the fact that the main aim of the chemotherapy is to eliminate remaining neoplastic cells from the organism, the success of this treatment determines the final result of the recovery process. One of the main reasons for unsuccessful chemotherapy outcomes is the resistance of the cancer cells to cytostatic or cytotoxic drugs. Many mechanisms are responsible for the resistance of cancer cells to cytostatics, among which the most recognized are expression of ABCtransporters, apoptosis mechanism disorders, DNA repair disorders, increased binding of the drugs in the cells, overexpression of protooncogenes, and decreased expression of tumor suppressors [1, 2]. P-gp dependant resistance is called typical MDR.

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