H7, an inhibitor of protein kinase C, inhibits tumour cell division in mice bearing ascitic Ehrlich's carcinoma.
We have previously shown that H7, an inhibitor of protein kinase C (PKC), inhibits proliferation of several cell lines as well as of primary cultured cells from human tumours. The aim of this work was to assess whether H7 is able to prevent the division of tumour cells in mice bearing Ehrlich's ascitic carcinoma. The LD50 of H7 injected intravenously was 61 mg/kg and 94 mg/kg for starved and fed mice, respectively. Acute intraperitoneal injection of 100 mg/kg of H7 decreased the number of mitoses in tumoral cells from ascitic fluid of mice bearing the carcinoma. The reduction was maximal (approximately 50%) after 90 min and then the number of mitosis rose due to a decrease in H7. Continuous delivery of H7 from mini-osmotic pumps implanted on the backs of the mice reduced the number of mitoses by approximately 65%, and the effect was maintained for approximately 24 h. The effect cannot be maintained for longer because H7 is unstable at body temperature. These results indicate that inhibition of PKC can block division of tumour cells in carcinoma-bearing animals, and support the idea that inhibitors of PKC could be useful for the clinical control of proliferation of certain tumours.
Instituto de Investigaciones Citologicas de la F.I.B., Valencia, Spain.
V
V
Felipo
M D
MD
Miñana
H
H
Cabedo
F
F
Perez-Minguez
A
A
Llombart-Bosch
S
S
Grisolía
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013997:Time Factors
D007546:Isoquinolines; D010879:Piperazines; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C