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Review
. 2021 Nov 26;10(12):3326.
doi: 10.3390/cells10123326.

Role of Natural Antioxidant Products in Colorectal Cancer Disease: A Focus on a Natural Compound Derived from Prunus spinosa, Trigno Ecotype

Maria Condello  1 , Stefania Meschini  1
Affiliations
Review

Role of Natural Antioxidant Products in Colorectal Cancer Disease: A Focus on a Natural Compound Derived from Prunus spinosa, Trigno Ecotype

Maria Condello et al. Cells. .

Abstract

Colorectal cancer (CRC) is on the rise in industrialized countries, which is why it is important to find new compounds that are effective, with little or no adverse health effects. CRC arises from some cells of the epithelium which, following a series of genetic or epigenetic mutations, obtain a selective advantage. This work consists of a review on endogenous and exogenous antioxidant products that may have an efficacy in the treatment of CRC and an experimental study, in which the treatment was carried out with a natural compound with antitumor and antiproliferative activity, Prunus spinosa Trigno ecotype, patented by us, on HCT116 colorectal carcinoma cell line. The superoxide content was quantified after the treatments at different concentrations (2, 5, or 10 mg/mL) by means of the DHR123 probe; loss of the mitochondrial membrane potential with the tetramethylrodamine methyl ester (TMRM) cationic probe and reduced glutathione content (GSH) from monochlorobimane (MCB). This study revealed the importance of a careful choice of the concentration of the natural compound to be used in the CRC, due to the presence of a paradoxical effect, both antioxidant and pro-oxidant, depending on the different physiological conditions of the cell.

Keywords: Prunus spinosa; antioxidant products; colorectal cancer cells; natural compounds.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Classification of antioxidants.
Figure 2
Figure 2
Schematic representation of the main reactions in which antioxidants are involved. Lipid peroxidation (red); Haber-Weiss reaction (green); Fenton reaction (light blue); SOD: superoxide dismutase; CAT: catalase.
Figure 3
Figure 3
Schematic representation of Glutathione. (A) interconversion between the reduced (GSH) and oxidized (GSSG) form of Glutathione. The role of nuclear factor-2 related erythroid factor-2 (Nrf2) in GSH metabolism under physiological conditions (B) and oxidative stress (C). GSH: reduced glutathione; GSSG: oxidized glutathione; GPx: glutathione peroxidase; GR: Glutathione reductase; KEAP1: Kelch-Like ECH Associated Protein 1.
Figure 4
Figure 4
Prunus spinosa Trigno ecotype (PsT) plant, from Bagnoli del Trigno, Molise, Italy.
Figure 5
Figure 5
Scanning electron microscopic observations of morphological changes induced by Prunus sp. extract on HCT116 cells. (A) untreated HCT116 cells; (B) HCT116 cells treated with PsT 10 mg/mL plus NAC for 24 h. Cells were fixed with glutaraldehyde and sucrose in cacodylate buffer. After post-fixation with OsO4 for 30 min, cells were dehydrated through graded ethanol concentration, critical point-dried in CO2 (CPD 030 Balzers device, Bal-Tec, Balzers), and gold coated by sputtering (SCD040 Balzers device, Bal-Tec). The observations were performed with a field emission gun scanning electron microscope (Quanta 200 Inspect, FEI Company, Eindhoven, The Netherlands). For detailed description see Condello et al., 2015 [67].
Figure 6
Figure 6
Flow cytometric analysis of oxidative stress after HCT116 cells treatment with increased concentration of Prunus spinosa extract plus nutraceutical activator complex (NAC) (PsT 2 mg/mL + NAC; PsT 5 mg/mL + NAC; PsT 10 mg/mL + NAC) for 1, 3 and 24h. (A) Superoxide content by dihydrorhodamine 123 (DHR123) probe; (B) hyperpolarized cell percentage by tetramethylrhodamine methyl ester (TMRM) cation probe; (C) depolarized cell percentage by tetramethylrhodamine methyl ester (TMRM) cation probe; (D) GSH content by monochlorobimane (MCB) probe. After treatment, cells were incubated with DHR123, or TMRM or MCB and then analyzed by a BDLSRII flow cytometer (Becton, Dickinson & Company, Franklin Lakes, NJ, USA). For detailed materials and methods see De Berardis et al., 2010 [73]. The results obtained from three independent experiments were expressed as mean±standard deviation. One-way Analysis of Variance (ANOVA), and Dunnett post hoc analysis are applied to reveal differences between all treated and control samples, using GraphPad Prism 5 software (GraphPad, San Diego, CA, USA). The alpha level was set at p < 0.05. *: p < 0.05 vs control.
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