Ultravioletradiationisthemaincauseofskincancers,andmelanomaisthemostseriousform of tumor.Thereisnotherapyforadvanced-stagemelanomaanditsmetastasisbecauseoftheirhigh resistance tovariousanticancertherapies.Humanskinisanimportantmetabolicorganinwhichoccurs photoinducedsynthesisofvitaminD3from7-dehydrocholesterol(7-DHC).7-DHC,theprecursorof cholesterolbiosynthesis,ishighlyreactiveandeasilymodifiable toproduce7-DHC-derivedcompounds. The intracellularlevelsof7-DHCoritsderivativescanhavedeleteriouseffectsoncellularfunctionality and viability.Inthisstudyweevaluatedtheeffectsonmelanomacelllinesof7-DHCassuchandforthis aim weusedmuchcaretominimize7-DHCmodifications. Wefoundthatfrom12to72hoftreatment 82–86% of7-DHCenteredthecells,andthelevelsof7-DHC-derivedcompoundswerenotsignificant. Simultaneously,reactiveoxygenspeciesproductionwassignificantly increasedalreadyafter2h.After 24 handupto72h,7-DHC-treatedmelanomacellsshowedareductionincellgrowthandviability.The cytotoxiceffectof7-DHCwasassociatedwithanincreaseinBaxlevels,decreaseinBcl-2/Baxratio, reduction ofmitochondrialmembranepotential,increaseinapoptosis-inducingfactorlevels,unchanged caspase-3 activity,andabsenceofcleavageofPARP-1.These findings couldexplainthemechanism through which7-DHCexertsitscytotoxiceffects.Thisisthe first reportinwhichthebiologicaleffects found inmelanomacellsaremainlyattributableto7-DHCassuch.
Evaluation of cytotoxic effects of 7-dehydrocholesterol on melanoma cells.
CORSO, GAETANO
2014-01-01
Abstract
Ultravioletradiationisthemaincauseofskincancers,andmelanomaisthemostseriousform of tumor.Thereisnotherapyforadvanced-stagemelanomaanditsmetastasisbecauseoftheirhigh resistance tovariousanticancertherapies.Humanskinisanimportantmetabolicorganinwhichoccurs photoinducedsynthesisofvitaminD3from7-dehydrocholesterol(7-DHC).7-DHC,theprecursorof cholesterolbiosynthesis,ishighlyreactiveandeasilymodifiable toproduce7-DHC-derivedcompounds. The intracellularlevelsof7-DHCoritsderivativescanhavedeleteriouseffectsoncellularfunctionality and viability.Inthisstudyweevaluatedtheeffectsonmelanomacelllinesof7-DHCassuchandforthis aim weusedmuchcaretominimize7-DHCmodifications. Wefoundthatfrom12to72hoftreatment 82–86% of7-DHCenteredthecells,andthelevelsof7-DHC-derivedcompoundswerenotsignificant. Simultaneously,reactiveoxygenspeciesproductionwassignificantly increasedalreadyafter2h.After 24 handupto72h,7-DHC-treatedmelanomacellsshowedareductionincellgrowthandviability.The cytotoxiceffectof7-DHCwasassociatedwithanincreaseinBaxlevels,decreaseinBcl-2/Baxratio, reduction ofmitochondrialmembranepotential,increaseinapoptosis-inducingfactorlevels,unchanged caspase-3 activity,andabsenceofcleavageofPARP-1.These findings couldexplainthemechanism through which7-DHCexertsitscytotoxiceffects.Thisisthe first reportinwhichthebiologicaleffects found inmelanomacellsaremainlyattributableto7-DHCassuch.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
