Induction of G1 phase arrest and apoptosis in MDA-MB-231 breast cancer cells by troglitazone, a synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligand.
Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPARgamma ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor alpha negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPARgamma ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G1 arrest in MDA-MB-231 cells exposed to troglitazone. An apoptotic effect by troglitazone demonstrated that apoptotic cells elevated by 2.5-fold from the control level at 10 microM, to 3.1-fold at 50 microM and to 3.5-fold at 75 microM. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D1, cyclin D2, cyclin D3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G1 arrest and apoptotic death of MDA-MB-231 cells.
Yu
Hong-Nu
HN
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonbuk, Jeonju 560-182, South Korea.
Lee
Young-Rae
YR
Noh
Eun-Mi
EM
Lee
Kyung-Sun
KS
Kim
Jong-Suk
JS
Song
Eun-Kyung
EK
Han
Myung-Kwan
MK
Lee
Yong-Chul
YC
Kwon
Kang-Beom
KB
Lee
Seung-Jin
SJ
Youn
Hyun Jo
HJ
Jung
Sung Hoo
SH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D008024:Ligands; D047495:PPAR gamma / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D000077288:Troglitazone
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D002839:Chromans; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D008024:Ligands; D047495:PPAR gamma; D018809:Proliferating Cell Nuclear Antigen; D045162:Thiazolidinediones; C413374:p27 antigen; D018844:Cyclin-Dependent Kinases; D000077288:Troglitazone