Elucidating the Molecular Mechanisms of Hederagenin-Regulated Mitophagy in Cervical Cancer SiHa Cells through an Integrative Approach Combining Proteomics and Advanced Network Association Algorithm

Hederagenin (Hed),
a natural triterpenoid, exhibits antitumor potential
in cervical cancer. The present study was designed to explore Hed’s
regulatory mechanisms on mitophagy in SiHa cervical cancer cells,
employing tandem mass tag (TMT) proteomics and an advanced network
association algorithm (NAA). Our findings revealed that Hed decreased
SiHa cell viability, induced apoptosis, and altered mitochondrial
membrane potential. Notably, Hed inhibited mitophagic flux under both
normoxic and hypoxic conditions. Through TMT proteomics analysis and
innovative NAA, we identified a close association between the HIF-1
signaling pathway and mitophagy. Network analysis further suggested
that Hed acts on a target network centered on SRC, STAT3, AKT1, and
HIF1A. Western blot analysis confirmed the expression and phosphorylation
status of these targets in response to Hed. This study elucidates
the molecular mechanisms underlying Hed’s regulation of mitophagy
in SiHa cells, offering novel insights and potential therapeutic targets
for cervical cancer treatment.