Abstract
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.
Highlights
POMx is a commercial pomegranate (Punica granatum L.)-derived polyphenols-rich aqueous extract powder (POM Wonderful, LLC, Los Angeles, CA, USA) [13,24]
The present study shows that the IC50 values at the 24 h ATP assay for POMx incubated three oral cancer cell lines (Ca9-22, HSC-3, and OC-2) were 80.53, 100.34, and 108.12 μg/mL, respectively (Figure 2)
POMx for three oral cancer cell lines (Figure 7A). Protein expressions for these antioxidant genes are downregulated at 72 h POMx treatment for oral cancer cells (HSC-3 and OC-2) but slightly upregulated for Ca9-22 cells (Figure 7B). These results suggest that mRNA and protein expressions for antioxidant signaling may be differentially regulated between different oral cancer cell lines
Summary
Pomegranate has gained extraordinary appreciation because of its ability to inhibit/. Prevent a wide variety of cancers [1,2,3]. Pomegranate (Punica granatum L.) fruits contain abundant polyphenols [4,5]. The knowledge base in fields such as nutrigenetics and nutrigenomics continuously expands at a rapid rate. Emerging scientific evidence enables us to obtain a better understanding of the significant pharmacological properties of bioactive constituents derived from plants such as pomegranate [6]. Pomegranate, due to its bioactive compounds, belongs to a group of functional foods [7]. POMx, is standardized with polyphenolic ellagitannin content, and its food safety is regarded as “generally recognized as being safe (GRAS)” by the U.S Food and Drug
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