Pomegranate Extract (POMx) Induces Mitochondrial Dysfunction and Apoptosis of Oral Cancer Cells

Peng, Sheng-Yao; Lin, Li‐Ching; Chen, Shu-Rong; Farooqı, Ammad Ahmad; Cheng, Yuan-Bin; Tang, Jen‐Yang; Chang, Hsueh‐Wei

doi:10.3390/antiox10071117

Cited by 25 publications

(29 citation statements)

References 61 publications

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“…The antiproliferative effect of the pomegranate phenolic extract was also observed against human oral cancer. The extract triggered the dysfunction of the mitochondria by damaging their membrane potential and inducing the apoptotic mechanism [53] Chlorogenic acid is an interesting antioxidant molecule due to its wide spectrum of healthy effects on some pathologies, from diabetes to cardiovascular disease and cancer [54]. The oral administration of green coffee, particularly rich in chlorogenic acid, in hypertensive rats reduced the systolic blood pressure dose dependently without inducing any modification in the normotensive control group [55].…”

Section: Discussionmentioning

confidence: 99%

Recovery from Food Waste—Biscuit Doughs Enriched with Pomegranate Peel Powder as a Model of Fortified Aliment

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Lozano-Sánchez

et al. 2022

Biology

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The aim of the present work is the characterization of biscuit doughs enriched with pomegranate peel powder (PPP) at 3 (PPP3) and 5 (PPP5) wt% in the prospect of developing a fortified aliment as a support of the therapy of chronic inflammatory diseases of the intestinal tract. The total phenolic content of the powder was preliminarily evaluated. Then, the main compounds present in the PPP were identified by HPLC-ESI-TOF-MS analysis, being mainly hydrolysable tannins. The PPP was then treated at 180 °C for 20 min to mimic the baking treatment, and its water-soluble fraction (PPPwsf) was then added in the Caco-2 cell culture as a model of the intestinal epithelial barrier to verify its dose-dependent toxicity, ability in counteracting the oxidative stress, and anti-inflammatory action. Rheological experiments were performed to predict the macroscopic behavior of the PPP-added doughs during lamination and biscuit baking. SEM investigations gave their contribution to the microscopic comprehension of the dough structure. Finally, a consumer panel composed by thirty volunteers was enrolled to express its opinion on the sensory agreeableness of the biscuits prepared with two different concentrations of PPP compared with the reference dough. The discussion is focused on the biological effects of the main components found in the PPP.

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Section: Discussionmentioning

confidence: 99%

Recovery from Food Waste—Biscuit Doughs Enriched with Pomegranate Peel Powder as a Model of Fortified Aliment

Nuzzo

Picone

Lozano-Sánchez

et al. 2022

Biology

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“…Oxidative stress is tightly associated with apoptosis and other forms of cell death. It has been shown that pomegranate extract induced adenosine triphosphate (ATP) depletion, subG1 accumulation, and apoptosis in oral cancer cell lines but showed no toxicity to normal oral cells [18]. The apoptotic mechanisms involved mitochondrial membrane potential disruption and mitochondrial superoxide generation associated with the differential downregulation of several antioxidant gene mRNA/protein expressions and mitochondrial DNA damage.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture

et al. 2022

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Pomegranate peel extract (PoPEx) has been shown to have antioxidant and anti-inflammatory properties, but its effect on the adaptive immune system has not been sufficiently investigated. In this study, the treatment of human peripheral blood mononuclear cells (PBMC) with PoPEx (range 6.25–400 µg/mL) resulted in cytotoxicity at concentrations of 100 µg/mL and higher, due to the induction of apoptosis and oxidative stress, whereas autophagy was reduced. At non-cytotoxic concentrations, the opposite effect on these processes was observed simultaneously with the inhibition of PHA-induced PBMC proliferation and a significant decrease in the expression of CD4. PoPEx differently modulated the expression of activation markers (CD69, CD25, ICOS) and PD1 (inhibitory marker), depending on the dose and T-cell subsets. PoPEx (starting from 12.5 µg/mL) suppressed the production of Th1 (IFN-γ), Th17 (IL-17A, IL-17F, and IL-22), Th9 (IL-9), and proinflammatory cytokines (TNF-α and IL-6) in culture supernatants. Lower concentrations upregulated Th2 (IL-5 and IL-13) and Treg (IL-10) responses as well as CD4+CD25hiFoxp3+ cell frequency. Higher concentrations of PoPEx increased the frequency of IL-10- and TGF-β-producing T-cells (much higher in the CD4+ subset). In conclusion, our study suggested for the first time complex immunoregulatory effects of PoPEx on T cells, which could assist in the suppression of chronic inflammatory and autoimmune diseases.

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“…When antioxidant signaling is suppressed, ROS are generally developed. For example, pomegranate extract downregulated several antioxidant signaling pathways, enhancing oxidative stress, in oral cancer cells [ 50 ]. Accordingly, SK2 may downregulate the antioxidant signaling pathway, inducing ROS generation.…”

Section: Discussionmentioning

confidence: 99%

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

et al. 2022

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The benzo-fused dioxabicyclo[3.3.1]nonane core is the central framework in several natural products. Using this core, we had developed a novel nitrated [6,6,6]tricycle-derived compound containing an n-butyloxy group, namely, SK2. The anticancer potential of SK2 was not assessed. This study aimed to determine the antiproliferative function and investigated possible mechanisms of SK2 acting on oral cancer cells. SK2 preferentially killed oral cancer cells but caused no harmful effect on non-malignant oral cells. After the SK2 exposure of oral cancer cells, cells in the sub-G1 phase accumulated. This apoptosis-like outcome of SK2 treatment was validated to be apoptosis via observing an increasing annexin V population. Mechanistically, apoptosis signalers such as pancaspase, caspases 8, caspase 9, and caspase 3 were activated by SK2 in oral cancer cells. SK2 induced oxidative-stress-associated changes. Furthermore, SK2 caused DNA damage (γH2AX and 8-hydroxy-2′-deoxyguanosine). In conclusion, a novel nitrated [6,6,6]tricycle-derived compound, SK2, exhibits a preferential antiproliferative effect on oral cancer cells, accompanied by apoptosis, oxidative stress, and DNA damage.

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Pomegranate Extract (POMx) Induces Mitochondrial Dysfunction and Apoptosis of Oral Cancer Cells

Cited by 25 publications

References 61 publications

Recovery from Food Waste—Biscuit Doughs Enriched with Pomegranate Peel Powder as a Model of Fortified Aliment

Recovery from Food Waste—Biscuit Doughs Enriched with Pomegranate Peel Powder as a Model of Fortified Aliment

Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture

Antiproliferation- and Apoptosis-Inducible Effects of a Novel Nitrated [6,6,6]Tricycle Derivative (SK2) on Oral Cancer Cells

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