Late type apoptosis and apoptosis free lethal effect of quercetin in human melanoma.
No satisfactory treatment is currently available for metastatic malignant melanoma. Recently, the flavonoid quercetin was suggested as a potential treatment due to its anti-tumorogenic properties. Some of these properties appeared to correspond to those published for UVB irradiation. To determine quercetin's long-term effects, type of apoptosis, and shared properties with UVB, we exposed Mel-Juso, M14, and G361 human melanoma cell-lines to a large range of quercetin or UVB doses, 20-400 microm and 25-1000 mJ/cm2 respectively. Apoptosis was measured for 4 consecutive d by flow cytometry and cell viability was studied by colony-forming assay. Quercetin decreased cell viability level in a dose-dependent manner to almost zero at 100 microm. Up to this concentration, it did not induce significant apoptosis nor did it decrease the survival-fractions below 90% during a 4 d follow-up. The data suggest that Quercetin is lethal to melanoma cells at concentrations that do not activate apoptosis during the first 4 d post-exposure and that quercetin's effects extend beyond the period of direct contact. Both quercetin and UVB induced late-type apoptosis at the upper range of the tested doses, but they do not appear to share all the pathways that they activate. Finally, this paper provides novel data showing that quercetin causes two different lethal effects on human melanoma cells, suggesting the activation of at least two different dose-depended mechanisms.
Rosner
Karli
K
Laboratory for Molecular Dermatology, Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark. kr29@bbh.hosp.dk
Röpke
Carsten
C
Pless
Vibeke
V
Skovgaard
Gunhild Lange
GL
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D011794:Quercetin / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D014466:Ultraviolet Rays
D011794:Quercetin