Troglitazone enhances tamoxifen-induced growth inhibitory activity of MCF-7 cells.
Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands have been identified as a potential source of therapy for human cancers. However, PPARgamma ligands have a limitation for breast cancer therapy, since estrogen receptor alpha (ER(alpha)) negatively interferes with PPARgamma signaling in breast cancer cells. Here we show that ER(alpha) inhihits PPARgamma transactivity and ER(alpha)-mediated inhibition of PPARgamma transactivity is blocked by tamoxifen, an estrogen receptor blocker. The activation of ER(alpha) with 17-beta-estradiol blocked PPRE transactivity induced by troglitazone, a PPARgamma ligand, indicating the resistance of ER(alpha)-positive breast cancer cells to troglitazone. Indeed, troglitazone inhibited the growth of ER(alpha)-negative MDA-MB-231 cells more than that of ER(alpha)-positive MCF-7 cells. Combination of troglitazone with tamoxifen led to a marked increase in growth inhibition of ER(alpha)-positive MCF-7 cells compared to either agent alone. Our data indicates that troglitazone enhances the growth inhibitory activity of tamoxifen in ER(alpha)-positive MCF-7 cells.
Yu
Hong-Nu
HN
Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
Noh
Eun-Mi
EM
Lee
Young-Rae
YR
Roh
Si-Gyun
SG
Song
Eun-Kyung
EK
Han
Myung-Kwan
MK
Lee
Yong-Chul
YC
Shim
In Kyong
IK
Lee
Seung Jin
SJ
Jung
Sung Hoo
SH
Kim
Jong-Suk
JS
Youn
Hyun Jo
HJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D004357:Drug Synergism; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008024:Ligands; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D008024:Ligands; D047495:PPAR gamma; D045162:Thiazolidinediones; D013629:Tamoxifen; D004958:Estradiol; D000077288:Troglitazone