Diorganotin(IV) and triorganotin(IV) complexes of meso-tetra(4-sulfonatophenyl)porphine induce apoptosis in A375 human melanoma cells.
The cytotoxic effect of several diorganotin(IV) and triorganotin(IV)-meso-tetra(4-sulfonatophenyl)porphine derivatives was tested and only the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS showed cytotoxicity on A375 human melanoma cells. To examine the pathway of (Bu(2)Sn)(2)TPPS or (Bu(3)Sn)(4)TPPS induced A375 cell death, DNA fragmentation analysis, Annexin V binding and PI uptake as well as caspases activation analysis by Western blot were carried out. A375 cells treated exhibited several typical characteristics of apoptosis. Both the (Bu(2)Sn)(2)TPPS and the (Bu(3)Sn)(4)TPPS compounds activate caspase-8 and caspase-9 leading to caspase-3 activation. Thus, we propose that these two porphirin derivatives lead to the apoptosis of human melanoma cells via both death receptor-mediated and mitochondrial apoptotic pathways.
Costa
Maria Assunta
MA
Istituto di Biomedicina e Immunolgia Molecolare Alberto Monroy, Consiglio Nazionale delle Ricerche (CNR), Via Ugo La Malfa 153, 90146 Palermo, Italy. costama@ibim.cnr.it
Pellerito
Lorenzo
L
Izzo
Vincenzo
V
Fiore
Tiziana
T
Pellerito
Claudia
C
Melis
Mario
M
Musmeci
Maria Teresa
MT
Barbieri
Giovanna
G
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008856:Microscopy, Fluorescence; D009947:Organotin Compounds / Q000494:pharmacology*; D011166:Porphyrins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009947:Organotin Compounds; D011166:Porphyrins; C016136:tetraphenylporphine sulfonate; D020169:Caspases