Apoptotic response of uveal melanoma cells upon treatment with chelidonine, sanguinarine and chelerythrine.
The benzophenanthridine alkaloids sanguinarine, chelerythrine and chelidonine were reported previously to provoke cell death in a variety of tumor cells suggesting their potential application as anticancer agents. Here we tested their effects on a primary human uveal melanoma cell line, OCM-1. Flow cytometric analysis of annexin V binding/PI exclusion and DNA fragmentation disclosed that all these alkaloids could induce apoptosis in OCM-1 cells. Moreover, necrotic cell death was also observed upon alkaloid treatment. As it was also evidenced by light microscopic inspection of cellular morphology, chelidonine primarily caused apoptosis, while sanguinarine and chelerythrine were effective via a so-termed bimodal cell death (apoptosis and primary necrosis). The relative efficiencies of the two modes depended on the applied dose. This study is the first implication for the possible use of these alkaloids in the therapy of uveal melanomas, for which no really efficient therapeutic regimen is available so far.
Kemény-Beke
Adám
A
Department of Ophthalmology, Research Center for Molecular Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, H-4012 Debrecen, Hungary.
Aradi
János
J
Damjanovich
Judit
J
Beck
Zoltán
Z
Facskó
Andrea
A
Berta
András
A
Bodnár
Andrea
A
D000470:Alkaloids / Q000494:pharmacology*; D017304:Annexin A5 / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053119:Benzophenanthridines; D001600:Berberine Alkaloids / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007546:Isoquinolines; D008545:Melanoma / Q000473:pathology*; D018613:Microscopy, Confocal; D009336:Necrosis; D010617:Phenanthridines / Q000494:pharmacology*; D014604:Uveal Neoplasms / Q000473:pathology*
D000470:Alkaloids; D017304:Annexin A5; D000970:Antineoplastic Agents; D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D007546:Isoquinolines; D010617:Phenanthridines; C062047:chelidonine; C005705:sanguinarine; C016299:chelerythrine