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.

Autore Pugliese

• Corso Gaetano

Tutti gli autori

• Gelzo M , Granato G , Albano F , Arcucci A , Dello Russo A , De Vendittis E , Ruocco MR , Corso G.

Titolo volume/Rivista

FREE RADICAL BIOLOGY & MEDICINE

Anno di pubblicazione

2014

ISSN

0891-5849

ISBN

Non Disponibile

Numero di citazioni Wos

5

Ultimo Aggiornamento Citazioni

Non Disponibile

Numero di citazioni Scopus

5

Ultimo Aggiornamento Citazioni

Non Disponibile

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile