Effects of BAPTA-AM, Forskolin, DSF and Z.VAD.fmk on PDT-induced apoptosis and m-THPC phototoxicity on B16 cells.
As many types of cells exposed to photodynamic therapy (PDT) appear to undergo apoptosis, various apoptosis inhibitors have already been used in studies of PDT-induced apoptosis. Although these inhibitors decrease apoptosis, their real effect on the phototoxic efficacy of photosensitisers is unclear. The good phototoxicity of m-THPC was confirmed on murine melanoma B16-A45 cells. Toxicity and phototoxicity studies were then carried out using four apoptosis inhibitors: BAPTA-AM, Forskolin, DSF, and Z.VAD.fmk. Although all inhibitors tested blocked PDT-induced apoptosis, none produced a significant modification of the phototoxic effect of m-THPC on B16 cells. It has been suggested that apoptosis and necrosis share common initiation pathways and that the final outcome is determined by the presence of an active caspase. This implies that apoptosis inhibition reorients cells to necrosis, i.e. those cells sufficiently damaged by PDT appear to be killed, regardless of the mechanism involved.
Thibaut
S
S
Département Laser, Hôpital Laënnec, 44093 Nantes, France.
Bourré
L
L
Hernot
D
D
Rousset
N
N
Lajat
Y
Y
Patrice
T
T
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D002614:Chelating Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D008545:Melanoma / Q000628:therapy; D008546:Melanoma, Experimental; D008652:Mesoporphyrins / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D010778:Photochemotherapy / Q000009:adverse effects*; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D002614:Chelating Agents; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D005576:Colforsin; D004533:Egtazic Acid; C072269:temoporfin; D004221:Disulfiram