Hypericin photoactivation triggers down-regulation of matrix metalloproteinase-9 expression in well-differentiated human nasopharyngeal cancer cells.
Recently, we have shown that hypericin-mediated photodynamic therapy (PDT) is a promising modality for the treatment of nasopharyngeal cancer (NPC). The present study evaluated the expression of matrix metalloproteinase-9 (MMP-9) following hypericin-PDT in well-differentiated HK1 NPC cells. Down-regulation of MMP-9 by hypericin-PDT was observed at the mRNA level in HK1 cells in vitro and in vivo and at the protein level in vitro. Transcriptional activities of the activator protein-1 (AP-1) and nuclear factor (NF)-kappaB regulatory elements were inhibited by PDT. We also found that PDT reduced secreted granulocyte-macrophage colony stimulating factor (GM-CSF), which is known to activate transcription of NK-kappaB and AP-1. However, incubation of untreated HK1 cells with exogenous GM-CSF abrogated the reduction of MMP-9 production in hypericin-PDT-treated cells. It would appear that PDT downregulates MMP-9 expression via inhibition of GM-CSF production, which in turn modulates AP1/NF-kappaB transcriptional activities. Suppression of MMP-9 by hypericin-PDT may have therapeutic implications.
Du
H-Y
HY
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Olivo
M
M
Mahendran
R
R
Huang
Q
Q
Shen
H-M
HM
Ong
C-N
CN
Bay
B-H
BH
D000818:Animals; D000873:Anthracenes; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D005347:Fibroblasts; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010569:Perylene / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010778:Photochemotherapy; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects
D000873:Anthracenes; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D010569:Perylene; C004965:hypericin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D020780:Matrix Metalloproteinase 9