-Solanine induces ferroptosis in nasopharyngeal carcinoma via targeting HSP90/p53 axis

a-Solanine, a natural small molecule compound, mainly derived from potato tubers with anti-tumor and antiinflammatory effects. No studies have yet confirmed that a-solanine can act on tumor cells via ferroptosis, and its molecular mechanism is unclear. The present study aimed to study whether a-solanine could induce nasopharyngeal carcinoma (NPC) cell death through ferroptosis and its specific molecular mechanism. Here, a-solanine was proven to trigger ferroptosis in NPC cells via targeting HSP90a directly. The primary manifestations of a-solanine-induced ferroptosis in NPC HK-1 and 5-8F cells were increased levels of ROS, MDA,iron and altered mitochondrial structure. Moreover, there was a noticeable decrease in SLC7A11 and GPX4 expression. Mechanistic study showed that a-solanine directly binds to HSP90a which promotes p53 expression and ultimately inhibits the level of SLC7A11 to inactivate GPX4. Collectively, our study revealed the potential application of a-solanine in the treatment of nasopharyngeal carcinoma through ferroptosis.