Isorhamnetin induces the paraptotic cell death through ROS and the ERK/MAPK pathway in OSCC cells

OBJECTIVE There were rarely investigations on the effects and molecular mechanisms of oral squamous cell carcinoma (OSCC) cells when treated with isorhamnetin. This article assesses the anticancer effect of isorhamnetin. METHODS AND MATERIALS OSCC cells were treated with or without isorhamnetin. Cell proliferation, cell cycle arrest, cell migration, cell death and the related signaling pathways were evaluated. RESULTS The results revealed that cell proliferation was inhibited in a dose- and time-dependent manner, which was confirmed by diminished cell viability and revealed by decreased in the number of cell colonies. In addition, the cell cycle arrested in the G2/M phase, and the protein levels of cyclin B1 and CDC2 were suppressed. Moreover, the cell migration was inhibited, and the protein levels of related proteins were modulated. Furthermore, it could be observed that abundant cytoplasmic vacuoles existed which that were derived from mitochondria and the endoplasmic reticulum. It was confirmed that cell death did not result from apoptosis, and may have which may be apt to paraptosis. Isorhamnetin was observed to upregulate phosphorylated ERK cascades and increase ROS levels. CONCLUSIONS Our study suggested that the anticancer effect of isorhamnetin might trigger paraptosis, which may indicate a new therapeutic approach to OSCC.