Antitumor effect of a new organic selenium compound, 6-phenyl-7 (6H)-isoselenazolo [4,3-d] pyrimidone (ISP), on the growth of P388 mouse leukemia.
The organic selenium compound, ISP [6-phenyl-7(6H)-isoselenazolo [4,3-d] pyrimidone] markedly inhibited the growth of P388 mouse leukemia at dose of 100 micrograms/mouse per day x 10 with no sign of toxicity. The antitumor activity of 4,5-dihydro-4-methyl-6-oxo-5-phenyl-6H-pyrazolo [4,5-c] isoselenazole (PIS) was weaker than that of ISP. The total lipid and phospholipid contents in the leukemic cells treated with ISP were significantly decreased. The fatty acid pattern of cholesterol esters, phosphatidyl choline and phosphatidyl ethanolamine from the ISP-treated P388 leukemic cells differed markedly from that of the corresponding lipids from the control leukemic cells. In addition, the synthesis of DNA or RNA was depressed in the ISP-treated leukemic cells. The present results indicate that ISP may open new perspectives in cancer chemotherapy.
Ito
H
H
Department of Pharmacology, Mie University School of Medicine, Japan.
Wang
J Z
JZ
Shimura
K
K
Sakakibara
J
J
Ueda
T
T
D000577:Amides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001393:Azoles; D005227:Fatty Acids / Q000032:analysis; D005260:Female; D007941:Leukemia P388 / Q000378:metabolism / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology*; D008055:Lipids / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009696:Nucleic Acids / Q000096:biosynthesis; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; D010743:Phospholipids / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D012643:Selenium / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000577:Amides; D000970:Antineoplastic Agents; D001393:Azoles; D005227:Fatty Acids; D008055:Lipids; D009696:Nucleic Acids; D009942:Organometallic Compounds; D016566:Organoselenium Compounds; D010743:Phospholipids; D011720:Pyrazoles; D011744:Pyrimidinones; C046552:6-phenyl-7(6H)-isoselenazolo(4,3-d)pyrimidone; C065228:4-methyl-3-phenylcarbamoyl-1,2,5-selenadiazole; C065227:4,5-dihydro-4-methyl-6-oxo-5-phenyl-6H-pyrazolo(4,5-c)isoselenazole; D012643:Selenium