Kaempferol induces mitophagy and disrupts iron metabolism via SFXN2 leading to apoptosis in multiple myeloma cells.

BACKGROUND

The role of kaempferol, a natural flavonoid, in the apoptosis of multiple myeloma cells has not been fully investigated. This study investigated the effects of kaempferol on MM cell apoptosis and its underlying mechanisms.

METHODS

In vitro, cell viability was measured using the CCK-8 and EdU assays, and apoptosis was assessed using flow cytometry. Mitochondrial damage and autophagy were analyzed using JC-1 staining, MitoTracker Green staining, and fluorescence microscopy. Western blot and qRT-PCR were used to assess SFXN2 and autophagy-related molecule levels. Intracellular Fe2+ levels were measured to determine the effect of kaempferol on iron metabolism. For the in vivo studies, the antitumor effects of kaempferol in combination with iron were assessed using a mouse xenograft model.

RESULTS

Kaempferol inhibited multiple myeloma cell proliferation and induced apoptosis in a dose-dependent manner. It significantly increased mitochondrial damage, enhanced mitochondrial autophagy, and accumulated intracellular Fe2+ levels. In addition, kaempferol decreased SFXN2 expression, which is associated with disturbed iron metabolism and enhanced mitochondrial autophagy. Kaempferol effectively inhibited tumor growth and promoted apoptosis in vivo, particularly when combined with iron.

CONCLUSION

Kaempferol was identified as a novel regulator of SFXN2, linking its natural activity to mitochondrial iron dysregulation and mitophagy in MM. Targeting the kaempferol-SFXN2 axis may represent a promising therapeutic strategy for multiple myeloma.