Growth inhibition of human osteosarcoma HuO9 cells by methylglyoxal bis(cyclopentylamidinohydrazone) in vitro and in vivo.
Polyamines are considered to be important intracellular molecules for the proliferation of cancer cells. In this study, effects of methyl-glyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a potent inhibitor of the polyamine biosynthetic pathway, on the growth of human osteosarcoma HuO9 cells have been investigated. MGBCP dose-dependently inhibited the growth of HuO9 cells, in which the contents of spermine, spermidine and putrescine decreased concomitantly. The MGBCP-treated cells clearly exhibited morphological changes, indicating the blebbing and chromatin condensation which are characteristic of apoptosis. Characteristic oligonucleosomal-sized DNA fragments were observed in the MGBCP-treated cells. In in vivo experiments MGBCP (20 or 50 mg/kg) inhibited the growth of transplanted HuO9 tumors in mice. These findings suggest that the inhibition of polyamine synthesis results in the suppression of growth of osteosarcoma HuO9 cells, eventually inducing apoptosis in these human osteosarcoma cells in vitro and in vivo.
Satoh
N
N
Department of Orthopedic Surgery, Mie University, Tsu-city, Mie 514-8507, Japan.
Hibasami
H
H
Mori
K
K
Kaneko
H
H
Wakabayashi
H
H
Hirata
K
K
Sonoda
J
J
Nakashima
K
K
Uchida
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015317:Biogenic Polyamines / Q000378:metabolism; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008935:Mitoguazone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015317:Biogenic Polyamines; C059234:methylglyoxal bis(cyclopentylamidinohydrazone); D008935:Mitoguazone