Effect of the protein kinase inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine H-7 and N-(2-[methylamino]ethyl)-5-isoquinoline-sulfonamide H-8 on Lewis lung carcinoma tumor progression.

Abstract	The effects of 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine H-7 (a cAMP-dependent protein kinase and protein kinase C inhibitor), n-(2-[methylamino]ethyl)-5-isoquinoline-sulfonamide H-8 (a cAMP- and cGMP-dependent protein kinase inhibitor) and indomethacin (IND, a cyclooxygenase inhibitor) on both the spontaneous metastatic ability of 3LL (Lewis lung carcinoma) tumor cells and anti-tumor host response were studied. The study of tumor progression showed that H-7 and H-8 (2 mg kg(-1) day(-1) , i.p., for 8 days) significantly reduced the mean number of metastases (0.8 +/- 0.2 and 1.0 +/- 0.7, respectively, P < 0.05) with respect to the number of lung metastases (4.2 +/- 2.1) observed in the control group. In turn, the highest tumor-specific cytotoxicity response (50% increase vs. non-treated target cells) was observed when both animal and tumor cells were treated with H-8. This suggests that the protein kinase inhibitors could inhibit tumor progression toward lung metastases formation by blocking the immunosuppressor mechanism triggered by agents that increase intracellular cAMP.
Authors	C Blaya, J Crespo, A Crespo, S F Aliño
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 354 Issue 1 Pg. 99-104 (Jul 31 1998) ISSN: 0014-2999 [Print] Netherlands
PMID	9726636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cyclooxygenase Inhibitors Enzyme Inhibitors Isoquinolines 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine N-(2-(methylamino)ethyl)-5-isoquinolinesulfonamide Indomethacin
Topics	1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (pharmacology) Animals Carcinoma, Lewis Lung (drug therapy, pathology) Cell Division (drug effects) Cyclooxygenase Inhibitors (pharmacology) Cytotoxicity, Immunologic (drug effects) Disease Progression Enzyme Inhibitors (pharmacology) Indomethacin (pharmacology) Isoquinolines (pharmacology) Leukocytes, Mononuclear (drug effects, immunology) Lymphocytes (drug effects, immunology) Male Mice Mice, Inbred C57BL Neoplasm Metastasis Neoplasm Transplantation Spleen (cytology, drug effects, immunology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!