Arsonoliposomes for the potential treatment of medulloblastoma.
OBJECTIVE
To investigate the arsonoliposome effect on medulloblastoma cells (VC312Rs) related to uptake, endocytotic mechanism and cell viability.


METHODS
VC312R viability in presence of either arsonoliposomes or stealth liposomes was studied using MTT assay for 1-4 days. Fibroblasts (3T3) were used as control. Apoptosis was studied for 2 h, 5 h and 24 h. Bodipy-labelled arsonoliposome uptake (time- and dose-dependent) was estimated using FACS analysis. The endocytotic mechanism was investigated using inhibitors of clathrin- (chlorpromazine) and caveolae-mediated endocytosis (filipin).


RESULTS
Arsonoliposomes affected significantly the VC312R viability compared to 3T3 cells and induced apoptosis to VC312Rs after 2 h of incubation. Apoptosis was not observed for 3T3 cells. Liposome uptake versus time showed a bimodal pattern. Clathrin-mediated endocytosis was the main endocytotic mechanism at low lipid concentrations and caveolae at higher ones; thus, dose-dependent uptake did not show a plateau at increased lipid concentrations.


CONCLUSIONS
Arsonoliposomes showed "selective" toxicity towards medulloblastoma cells inducing apoptosis after 2 hs of incubation. Therefore, arsonoliposomes are promising anticancer vehicles for brain tumour treatment.
Favretto
Marco E
ME
Medway School of Pharmacy, University of Kent, Central Avenue, Chatham Maritime, Kent, ME4 4TB, UK.
Marouf
Showan
S
Ioannou
Panagiotis
P
Antimisiaris
Sophia G
SG
Parker
Terence L
TL
Kallinteri
Paraskevi
P
D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001152:Arsenicals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000502:physiology; D008081:Liposomes; D008527:Medulloblastoma / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001152:Arsenicals; D008081:Liposomes