Indole-3-carbinol enhances ultraviolet B-induced apoptosis by sensitizing human melanoma cells.
Indole-3-carbinol (I3C) has been found to act against several types of cancer, while ultraviolet B (UVB) is known to induce the apoptosis of human melanoma cells. Here, we investigated whether I3C can sensitize G361 human melanoma cells to UVB-induced apoptosis. We examined the effects of combined I3C and UVB (I3C/UVB) at various dosages. I3C (200 microM)/UVB (50 mJ/cm(2)) synergistically reduced melanoma cell viability, whereas I3C (200 microM) or UVB (50 mJ/cm(2)), separately, had little effect on cell viability. DNA fragmentation assays indicated that I3C/UVB induced apoptosis. Further results show that I3C/UVB activates caspase-8, -3, and Bid and causes the cleavage of poly(ADP-ribose) polymerase. Moreover, I3C decreased the expression of the anti-apoptotic protein, Bcl-2, whereas UVB increased the translocation of Bax to mitochondria. Thus, an increased Bax/Bcl-2 ratio by I3C/UVB may result in melanoma apoptosis. In conclusion, our study demonstrated that I3C sensitizes human melanoma cells by down-regulating Bcl-2.
Kim
D-S
DS
Department of Dermatology, Seoul National University Bundang Hospital, 300 Gumi-Dong, Bundang-Gu, Seongnam-Si, Gyeonggi-Do 463-707, Korea.
Jeong
Y-M
YM
Moon
S-I
SI
Kim
S-Y
SY
Kwon
S-B
SB
Park
E-S
ES
Youn
S-W
SW
Park
K-C
KC
D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004357:Drug Synergism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D051023:BH3 Interacting Domain Death Agonist Protein; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C016517:indole-3-carbinol; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053181:Caspase 8