α-Solanine induces ferroptosis in nasopharyngeal carcinoma via targeting HSP90α/p53 axis

Abstract

α-Solanine, a natural small molecule compound, mainly derived from potato tubers with anti-tumor and anti-inflammatory effects. No studies have yet confirmed that α-solanine can act on tumor cells via ferroptosis, and its molecular mechanism is unclear. The present study aimed to study whether α-solanine could induce nasopharyngeal carcinoma (NPC) cell death through ferroptosis and its specific molecular mechanism. Here, α-solanine was proven to trigger ferroptosis in NPC cells via targeting HSP90α directly. The primary manifestations of α-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 α-solanine directly binds to HSP90α which promotes p53 expression and ultimately inhibits the level of SLC7A11 to inactivate GPX4. Collectively, our study revealed the potential application of α-solanine in the treatment of nasopharyngeal carcinoma through ferroptosis.

Keywords

• Nasopharyngeal carcinoma
• α-Solanine
• Ferroptosis
• HSP90α
• p53