Stress response, survival and enhancement of heat sensitivity in a human melanoma cell line treated with L-canavanine.
L-Canavanine, like other aminoacid analogs, induces the synthesis of heat shock proteins (HPSs) but, unlike heat or other stressing agents, it fails to induce thermotolerance. We have studied the synthesis and the intracellular distribution of HSPs induced by canavanine, the effects of this analog on the viability and thermal sensitivity of a human melanoma cell line (M14) and the capacity of canavanine-induced HSPs to self regulate their own synthesis. Evidence indicates that the HSP induction is time--and dose--dependent and, also in the presence of arginine, is not associated with the development of thermotolerance. On the contrary, cells become more heat sensitive and are less efficient in the control of the feed-back mechanism that regulates HSP synthesis. The possible utilization of this substance as a potential aid for the treatment of tumors, in association with heat, was examined.
Mattei
E
E
Istituto Tecnologie Biomediche, C.N.R., Rome, Italy.
Damasi
D
D
Mileo
A M
AM
Delpino
A
A
Ferrini
U
U
D002172:Canavanine / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D006706:Homeostasis; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008545:Melanoma; D008970:Molecular Weight; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D002172:Canavanine