The anticancer effect of pomegranate polyphenolic extract POMx in
oral cancer cells has rarely been explored, especially where its impact on mitochondrial functioning is concerned. Here, we attempt to evaluate the proliferation modulating function and mechanism of POMx against human
oral cancer (Ca9-22, HSC-3, and OC-2) cells. POMx induced
ATP depletion, subG1 accumulation, and
annexin V/Western blotting-detected apoptosis in these three
oral cancer cell lines but showed no toxicity to normal oral cell lines (HGF-1). POMx triggered mitochondrial membrane potential (MitoMP) disruption and mitochondrial
superoxide (
MitoSOX) generation associated with the differential downregulation of several
antioxidant gene
mRNA/
protein expressions in
oral cancer cells. POMx downregulated mitochondrial mass,
mitochondrial DNA copy number, and mitochondrial biogenesis gene
mRNA/
protein expression in
oral cancer cells. Moreover, POMx induced both PCR-based
mitochondrial DNA damage and γH2AX-detected nuclear DNA damage in
oral cancer cells. In conclusion, POMx provides antiproliferation and apoptosis of
oral cancer cells through mechanisms of mitochondrial impairment.