Changes in diacylglycerol and membrane associated protein kinase C activity reflect the growth status of xenografted human mammary carcinoma treated with 8-Cl-cAMP.
The intracellular accumulation of cAMP inhibits the growth of transformed cells in vitro and in vivo, and exposure to various cAMP analogs produces similar results. The influence of such analogs on the growth of neoplastic cells in vivo is less well defined, and the relevance of these analogs for the phosphoinositide pathway has not been established. The present report details the inhibition of tumor growth that occurred when human mammary xenografts were treated with 8-Cl-cAMP, the subsequent rebound in tumor growth that occurred when treatment ceased, and the levels of diacylglycerol and membrane-associated protein kinase C activity that characterized tumors in different growth states. Tumor levels of diacylglycerol and particulate PKC activity appeared to be influenced not only by treatment but also by treatment withdrawal. Changes in these entities tended to coincide with tumor growth rate, being relatively suppressed during growth stasis and markedly elevated during periods of rapid growth. The data presented do not establish a causal relationship. Thus, the concomitant changes noted in tumor growth and tumor levels of either diacylglycerol and membrane-associated protein kinase C may only be coincidental. Alternatively, they may indicate that cAMP analogs inhibit tumor growth in vivo by modulating the phosphoinositide pathway.
Parandoosh
Z
Z
ICN Nucleic Acid Research Institute, Costa Mesa, CA 92626.
Rubalcava
B
B
Finch
R A
RA
Robins
R K
RK
Avery
T L
TL
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000201:enzymology; D004075:Diglycerides / Q000032:analysis*; D005260:Female; D005989:Glycerides / Q000032:analysis*; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000032:analysis / Q000473:pathology*; D051379:Mice; D009368:Neoplasm Transplantation; D011493:Protein Kinase C / Q000032:analysis*; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D004075:Diglycerides; D005989:Glycerides; D015124:8-Bromo Cyclic Adenosine Monophosphate; C044258:8-chloro-cyclic adenosine monophosphate; D011493:Protein Kinase C