Tamoxifen enhances apoptotic effect of cisplatin on primary endometrial cell cultures.
BACKGROUND
Cisplatin (CDDP) dose-limited by its side-effects is, in some instances, synergistically amplified when combined with tamoxifen (TAM). TAM has been shown to modulate apoptotic pathways of normal endometrial cells, whereas CDDP induces apoptosis in malignant endometrial cells. Their combined effect on normal or malignant endometrium is as yet unknown. This study aimed to evaluate the combined CDDP and TAM's apoptotic effect on normal endometrial tissue in the context of hormonal milieu.


METHODS
Primary endometrial cell cultures were established and maintained both in the presence and absence of steroidal hormones. The cultures were treated for 24 hours with 20 microM TAM and 50 microM CDDP as single drugs and in combination. Apoptosis was determined by evaluation of pre G1 cell populations in the cell cycle analysis with flow cytometer.


CONCLUSIONS
CDDP induced apoptosis in all cultures regardless of hormonal environment, while TAM significantly enhanced CDDP-induced apoptosis in steroidal deficient media in an additive manner. These are novel findings depicting CDDP's effect on normal endometrium, singularly and combined with TAM.
Drucker
Liat
L
Oncogenetics Laboratory, Sapir Medical Center, Meir Hospital, Kfar Sava, 44281, Israel. Druckerl@clalit.org.il
Stackievicz
Rodica
R
Radnay
Judith
J
Shapira
Hava
H
Cohen
Ilan
I
Yarkoni
Shai
S
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D006801:Humans; D013256:Steroids / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D020847:Estrogen Receptor Modulators; D013256:Steroids; D013629:Tamoxifen; D002945:Cisplatin