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Indole-6-carboxaldehyde isolated from Sargassum thunbergii inhibits the expression and secretion of matrix metalloproteinase-9

  • Tae‑Hee Kim (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE) ;
  • Soo-Jin Heo (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE) ;
  • Seok-Chun Ko (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE) ;
  • Won Sun Park (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE) ;
  • Il-Whan Choi (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE) ;
  • Myunggi Yi (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE) ;
  • Won-Kyo Jung (INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE)
  • Published : 20191100

Abstract

Sargassum thunbergii is a brown alga from which various bioactive compounds can be extracted. Among these, the activities of indole derivatives, particularly as potential inhibitors of matrix metalloproteinases (MMPs), and their underlying mechanisms have been rarely investigated. Therefore, we evaluated the inhibitory effects of indole-6-carboxaldehyde (I6CA) on MMP-9 by gelatin zymography and western blot anlaysis. We used phorbol 12-myristate 13-acetate (PMA), which is known to induce MMP-9 expression and secretion, to stimulate HT1080 cells. Our results revealed that I6CA significantly inhibited MMP-9 expression and secretion, without significantly affecting the viability of PMA-stimulated HT1080 cells. Our mechanistic studies indicated that I6CA suppressed the phosphorylation and activation of two mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK). Furthermore, I6CA inhibited the phosphorylation of inhibitor of κBα (IκBα) in response to PMA stimulation, which suppressed nuclear factor-κB (NF-κB) p65 subunit nuclear translocation. Collectively, I6CA was determined to suppress MMP-9 expression and secretion, and effects were proposed to be mediated via the inhibition of the MAPK and NF-κB p65 pathways. Therefore, we suggested I6CA to be a potential therapeutic agent for MMP-9-related processes, including tumor invasion and metastasis; however, further investigation is required.

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Acknowledgement

This research was supported by a research grant from the Marine Biotechnology Program (grant. no. 20150220) of the Ministry of Oceans and Fisheries of Republic of Korea and partially supported by a research grant from the Korea Institute of Ocean Science and Technology (grant. no. PE99722).