Antineoplastic activity of 2-methoxyestradiol in human pancreatic and gastric cancer cells with different multidrug-resistant phenotypes.
OBJECTIVE
Chemoresistance often leads to loss of the last treatment option for cancer. 2-Methoxyestradiol (2-ME2) has been shown to inhibit tumor growth. The aim was to examine the efficacy of 2-ME2 on multidrug-resistant human cells from pancreatic and gastric cancer.


METHODS
We investigated the impact of 2-ME2 on multidrug-resistant cells derived from human pancreatic and gastric cancer cells that were positive or negative for the MDR1-gene.


RESULTS
In pancreatic cancer cells, growth inhibition was 57% in parental, 72% in MDR1-negative and 87% in MDR1-positive cells after 1 micromol/L 2-ME2. In gastric cancer cells we found a growth inhibition of 75% in parental, 82% in MDR1-positive and 95% in MDR1-negative cells. Strong induction of apoptosis was induced after a low dose of 2-ME2. No significant difference in the amount of apoptotic cells was observed between parental and multidrug-resistant cells of both tumor types. The number of apoptotic cells after 2-ME2 ranged from 7.5% in parental gastric cancer cells to 20.1% in MDR1-negative gastric cancer cells.


CONCLUSIONS
2-ME2 may therefore have clinical application for chemoresistant cancer.
Schumacher
Guido
G
Department of General, Visceral, and Transplantation Surgery, Charité Campus Virchow Klinikum, Berlin, Germany. guido.schumacher@charite.de
Hoffmann
Janine
J
Cramer
Thorsten
T
Spinelli
Antonino
A
Jacob
Dietmar
D
Bahra
Marcus
M
Pratschke
Johann
J
Pfitzmann
Robert
R
Schmidt
Sven
S
Lage
Hermann
H
D000077584:2-Methoxyestradiol; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010641:Phenotype; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol