Effects of 17beta-estradiol on the cytotoxicity of etoposide in a lung carcinoma cell line and its bioavailability in ovariectomized Sprague-Dawley rats.
BACKGROUND
The activity of steroid hormones for the efficacy of antineoplastic drugs used in lung cancer treatment has not been explored. We evaluated the influence of 17beta-estradiol on the cytotoxicity of etoposide in a lung cancer cell line (A-549) and determined systemic levels of etoposide in vivoafter pretreatment with this hormone.


METHODS
The effect of 17beta-estradiol alone and combined with etoposide on cellular proliferation was evaluated. Blood levels of etoposide were studied in ovariectomized female rats previously treated with 17beta-estradiol. Etoposide levels were determined by high-performance liquid chromatography, and a pharmacokinetic analysis was performed.


RESULTS
17beta-Estradiol showed a tendency towards an increase in cellular proliferation but did not change the cytotoxic effect of etoposide. This in vivo study demonstrated that the blood levels of etoposide significantly decreased in the 17beta-estradiol-treated group.


CONCLUSIONS
The clear reduction in the in vivo systemic levels of etoposide in the presence of 17beta-estradiol suggests a possible role of this hormone in drug resistance. However, as these data cannot be extrapolated to clinic situations, more research is necessary to understand the interaction between hormonal compounds and antineoplastic drugs.
Guerrero-Vargas
N N
NN
Subdirección de Investigación Básica, Instituto Nacional de Cancerología, México DF, México.
Jurado
R
R
Virto-Aguilar
J
J
García-López
P
P
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000633:toxicity*; D001682:Biological Availability; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology*; D005047:Etoposide / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000972:Antineoplastic Agents, Phytogenic; D004958:Estradiol; D005047:Etoposide