Intracellular signalling: phosphatidylinositol lipid metabolism in cancer cells.
Evidence for heightened capacity for signal transduction in rat hepatoma as well as in human breast and ovarian carcinoma cells as reflected by coordinate increases in PI kinase and PIP kinase in the PI phosphorylation sequence leading to the production of second messengers IP3 and DAG is shown. The linkage of signal transduction enzymes with malignant growth is also seen as MDA-MB- 435 human breast carcinoma or ovarian OVCAR-5 cells express their proliferative capacity in tissue culture in the log phase. In both cases, quercetin inhibit cell proliferation with a decline in PI kinase activity and IP3 levels preceding the growth inhibition seen with quercetin. The elevated steady state activities of PI and PIP kinase indicate a metabolic up-regulation in signal transduction capacity of cancer cells which is down-regulated by quercetin. Since the gain in function manifested in the over-expressed capacity for signal transduction confers selective growth advantage to cancer cells, increased activities of PI and PIP kinases may be considered as sensitive targets for cancer chemotherapy. The potential of quercetin as an interceptor of intracellular signal transduction mechanisms needs to be explored.
Singhal
R L
RL
New Drug Discovery Research, Ranbaxy Research Laboratories, New Delhi, India.
Prajda
N
N
Weber
G
G
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D010716:Phosphatidylinositols; D011794:Quercetin; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; C020077:1-phosphatidylinositol-4-phosphate 5-kinase