Indole-3-carbinol and ultraviolet B induce apoptosis of human melanoma cells via down-regulation of MITF.
We investigated the mechanism of indole-3-carbinol (13C)/ultraviolet B (UVB)-induced apoptosis using SK-MEL-2 and SK-MEL-5 human melanoma cells. 13C/UVB significantly reduced the viability of SK-MEL-2 cells, whereas it had little influence on SK-MEL-5 cells. Correspondingly, cell cycle analysis showed that 13C/UVB induced a clear increase in the sub-G0/G1 phase in SK-MEL-2 cells. Furthermore, 13C/UVB activated caspase-9, caspase-8, caspase-3, and Bid and caused the cleavage of poly(ADP-ribose) polymerase (PARP) in SK-MEL-2 cells. In contrast, 13C/UVB showed no effects on the apoptotic signaling pathways in SK-MEL-5 cells. Moreover, we found that 13C down-regulated the microphthalmia-associated transcription factor (MITF) in SK-MEL-2 cells, but not in SK-MEL-5 cells. Next, to investigate the involvement of MITF in 13C/UVB-induced apoptosis, MITF silencing was conducted using small interfering RNA (siRNA) for MITF in SK-MEL-5 cells. Interestingly, 13C/UVB dramatically decreased the viability of MITF-down-regulated SK-MEL-5 cells. These results indicate that MITF plays a critical role in melanoma cell survival.
Department of Biochemistry, Chung-Ang University College of Medicine Seoul, Republic of Korea.
So-Young
SY
Kim
Dong-Seok
DS
Kima
Yun-Mi
YM
Jeong
Sang-Ik
SI
Moon
Sun-Bang
SB
Kwon
Kyoung-Chan
KC
Park
D000199:Actins / Q000096:biosynthesis; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000532:radiotherapy*; D051739:Microphthalmia-Associated Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014466:Ultraviolet Rays
D000199:Actins; D016588:Anticarcinogenic Agents; D007211:Indoles; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C016517:indole-3-carbinol; D020169:Caspases