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Sulforaphane Suppresses the Nicotine-Induced Expression of the Matrix Metalloproteinase-9 via Inhibiting ROS-Mediated AP-1 and NF-κB Signaling in Human Gastric Cancer Cells.

Abstract
Sulforaphane, a natural phytochemical compound found in various cruciferous vegetables, has been discovered to present anti-cancer properties. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in gastric cancer metastasis. However, the role of sulforaphane in MMP-9 expression in gastric cancer is not yet defined. Nicotine, a psychoactive alkaloid found in tobacco, is associated with the development of gastric cancer. Here, we found that sulforaphane suppresses the nicotine-mediated induction of MMP-9 in human gastric cancer cells. We discovered that reactive oxygen species (ROS) and MAPKs (p38 MAPK, Erk1/2) are involved in nicotine-induced MMP-9 expression. AP-1 and NF-κB are the critical transcription factors in MMP-9 expression. ROS/MAPK (p38 MAPK, Erk1/2) and ROS functioned as upstream signaling of AP-1 and NF-κB, respectively. Sulforaphane suppresses the nicotine-induced MMP-9 by inhibiting ROS-mediated MAPK (p38 MAPK, Erk1/2)/AP-1 and ROS-mediated NF-κB signaling axes, which in turn inhibit cell invasion in human gastric cancer AGS cells. Therefore, the current study provides valuable evidence for developing sulforaphane as a new anti-invasion strategy for human gastric cancer therapy.
AuthorsShinan Li, Pham Ngoc Khoi, Hong Yin, Dhiraj Kumar Sah, Nam-Ho Kim, Sen Lian, Young-Do Jung
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 9 (May 05 2022) ISSN: 1422-0067 [Electronic] Switzerland
PMID35563563 (Publication Type: Journal Article)
Chemical References
  • Isothiocyanates
  • NF-kappa B
  • Reactive Oxygen Species
  • Sulfoxides
  • Transcription Factor AP-1
  • Nicotine
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9
  • sulforaphane
Topics
  • Humans
  • Isothiocyanates
  • MAP Kinase Signaling System
  • Matrix Metalloproteinase 9 (metabolism)
  • NF-kappa B (metabolism)
  • Nicotine (pharmacology)
  • Reactive Oxygen Species (metabolism)
  • Stomach Neoplasms (drug therapy)
  • Sulfoxides
  • Transcription Factor AP-1 (metabolism)
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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