Phosphorylation of the fission protein Drp1 contributes to the impact of the curcuminoid 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one on mitochondrial and cellular processes

Curcumin and its curcuminoid derivatives extracted from turmeric have been investigated for their potential therapeutic benefits in cancer treatment. Curcuminoids 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one and bisdemethoxycurcumin can be obtained from <i>Alpinia galangal</i>. Despite their similar chemical structures, the effects of these curcuminoids on cellular functions and their therapeutic potential require further characterization. This study examined the impact of 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one and bisdemethoxycurcumin on human cancer cell lines and mouse embryonic fibroblasts. Our findings suggest that curcuminoids induce a shift in mitochondria dynamics toward fission. Exposure to curcuminoids resulted in attenuated mitochondrial activity, decreased mitochondrial mass, reduced reactive oxygen species (ROS) levels, and decreased membrane potential, accompanied by alterations in Drp1 phosphorylation. Notably, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one had more pronounced effects than curcumin and bisdemethoxycurcumin. Curcuminoids derived from <i>Alpinia galangal</i> influence mitochondrial function and cell survival through Drp1 phosphorylation, indicating their potential for cancer therapy via the modulation of mitochondrial function.