蘿蔔硫素藉由半胱胺酸蛋白質酵素 Cathepsin S 調控人類口腔癌細胞轉移

蘿蔔硫素(Sulforaphane)已被證實可以參與在許多生物反應，如神經保護、抗發炎作用、以及抗癌反應等等。然而，蘿蔔硫素對於人類口腔癌細胞的轉移以及其潛在機制並不清楚。在本篇研究中，我們觀察到蘿蔔硫素可以透過降低組織蛋白酶S(cathepsin S)的表現來降低口腔癌細胞株SCC-9與SCC-14的移動性與侵襲性。此外，蘿蔔硫素增加了維管相關蛋白1輕鏈3(light chain 3, LC3)的轉換，我們也使用了LC3的siRNA將LC3的基因下調，使得細胞的移動力增加。關於此機制，蘿蔔硫素是透過細胞外信號調節激酶extracellular signal-regulated kinase, ERK）路徑來抑制口腔癌細胞的移動性，將其抑制亦可反轉其細胞移動性。總之，蘿蔔硫素透過細胞外信號調節激酶誘導細胞自噬作用進而抑制組織蛋白酶S的表現；因此組織蛋白酶S以及LC3也許可以成為口腔癌治療上的新標靶目標。

Sulforaphane has been demonstrated to exert numerous biological effects, such as neuroprotective, anti-inflammatory, and anticancer effects. However, the detailed effects of sulforaphane on human oral cancer cell migration and the underlying mechanisms remain unclear. In this study, we observed that sulforaphane attenuated SCC-9 and SCC-14 cell motility and invasiveness by reducing cathepsin S expression. Moreover, sulforaphane increased microtubule-associated protein 1 light chain 3 (LC3) conversion, and the knockdown of LC3 by siRNA increased cell migration ability. Regarding the mechanism, sulforaphane inhibited the cell motility of oral cancer cells through the extracellular signal-regulated kinase (ERK) pathway, which in turn reversed cell motility. In conclusion, sulforaphane suppress cathepsin S expression by inducing autophagy through ERK signaling pathway. Thus, cathepsin S and LC3 may be new targets for oral cancer treatment.