Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 61469, Korea.
Faculty of Basic Medical Sciences, Pham Ngoc Thach University of Medicine, Ho Chi Minh City 740500, Vietnam.
Int J Mol Sci. 2022 May 5;23(9):5172. doi: 10.3390/ijms23095172.
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.
西兰花中的天然植物化学物质萝卜硫素具有抗癌特性。基质金属蛋白酶-9（MMP-9）在胃癌转移中起着关键作用。然而，萝卜硫素对胃癌中 MMP-9 表达的作用尚不清楚。烟草中的活性生物碱尼古丁与胃癌的发展有关。在这里，我们发现萝卜硫素抑制了人胃癌细胞中尼古丁介导的 MMP-9 的诱导。我们发现活性氧（ROS）和 MAPKs（p38 MAPK、Erk1/2）参与了尼古丁诱导的 MMP-9 表达。AP-1 和 NF-κB 是 MMP-9 表达的关键转录因子。ROS/MAPK（p38 MAPK、Erk1/2）和 ROS 分别作为 AP-1 和 NF-κB 的上游信号。萝卜硫素通过抑制 ROS 介导的 MAPK（p38 MAPK、Erk1/2）/AP-1 和 ROS 介导的 NF-κB 信号轴来抑制尼古丁诱导的 MMP-9，从而抑制人胃癌 AGS 细胞的侵袭。因此，本研究为开发萝卜硫素作为人类胃癌治疗的新的抗侵袭策略提供了有价值的证据。
