Platelet-activating factor induces up-regulation of antiapoptotic factors in a melanoma cell line through nuclear factor-kappaB activation.
In this study, we investigated the influence of platelet-activating factor (PAF) on the induction of apoptosis-regulating factors in B16F10 melanoma cells. PAF increased the expression of mRNA and the protein synthesis of antiapoptotic factors, such as Bcl-2 and Bcl-xL, but did not increase the expression of the proapoptotic factor, Bax. A selective nuclear factor-kappaB (NF-kappaB) inhibitor, parthenolide, inhibited the effects of PAF. Furthermore, PAF inhibited etoposide-induced increases in caspase-3, caspase-8, and caspase-9 activities, as well as cell death. p50/p65 heterodimer increased the mRNA expression of Bcl-2 and Bcl-xL and decreased etoposide-induced caspase activities and cell death. In an in vivo model in which Matrigel was injected s.c., PAF augmented the growth of B16F10 cells and attenuated etoposide-induced inhibition of B16F10 cells growth. These data indicate that PAF induces up-regulation of antiapoptotic factors in a NF-kappaB-dependent manner in a melanoma cell line, therefore suggesting that PAF may diminish the cytotoxic effect of chemotherapeutic agents.
Heon Seo
Kook
K
Department of Biological Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju, Republic of Korea.
Ko
Hyun-Mi
HM
Kim
Han-A
HA
Choi
Jung-Hwa
JH
Jun Park
Sung
S
Kim
Kyoung-Jin
KJ
Lee
Hern-Ku
HK
Im
Suhn-Young
SY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004347:Drug Interactions; D005047:Etoposide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012717:Sesquiterpenes / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000096:biosynthesis / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C494812:Bcl2l1 protein, mouse; D061945:Caspase Inhibitors; D016328:NF-kappa B; D010972:Platelet Activating Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012717:Sesquiterpenes; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C002669:parthenolide; D005047:Etoposide; D020169:Caspases