Involvement of apoptosis and cyclin D1 gene repression in growth inhibition of T-47D human breast cancer cells by methylglyoxal bis(cyclopentylamidinohydrazone).
Polyamines are considered to be important intracellular molecules for the proliferation of the cancer cells. In this study, effects of methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a potent inhibitor of the polyamine biosynthetic pathway, on the growth and cell cycle of T-47D human breast cancer cells were investigated. MGBCP dose-dependently inhibited the growth of T-47D cells, in which the contents of spermine, spermidine and putrescine decreased concomitantly. The gene expression of cyclin D1 was also repressed by the MGBCP treatment. The MGBCP-treated cells clearly exhibited morphological changes indicating the blebbing and chromatin condensation which are characteristic of apoptosis. Flow cytometric analysis showed hypo-diploid subpopulations due to apoptotic cells, and characteristic oligonucleosomal-sized DNA fragments were clearly observed for MGBCP-treated cells as the concentration of the drug was increased. These findings suggest that the inhibition of polyamine synthesis results in the repressions of cyclin D1 expression and cell cycle progression, eventually inducing apoptosis in these human breast cancer cells.
Kaneko
H
H
Department of Biochemistry and First Surgery, Faculty of Medicine, Mie University, Tsu-city, Mie 514-8507, Japan.
Hibasami
H
H
Satoh
N
N
Wakabayashi
H
H
Ikeda
H
H
Tsuge
N
N
Yonemaru
K
K
Muraki
A
A
Kawarada
Y
Y
Nakashima
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D011073:Polyamines; D012333:RNA, Messenger; C059234:methylglyoxal bis(cyclopentylamidinohydrazone); D019938:Cyclin D1; D008935:Mitoguazone