Abstract

Cancer is the second cause of death worldwide. Among cancers, hepatocellular carcinoma is one of the most prevalent. Evidence indicates that the daily consumption of fruits and vegetables can prevent the onset of various cancers due to the presence of bioactive compounds. Sweet cherries are known for their richness in phenolics, including anthocyanins, which are the major constituents, and presumably, the key contributors to their biological activity. Therefore, the present study aimed to evaluate the effects of three different cherry fractions on human hepatocellular carcinoma (HepG2) cells viability and effectiveness to improve the redox status of these cells under oxidative damage induced by nitric oxide radicals and hydrogen peroxide. Phenolic characterization of fractions was performed by Fourier transform infrared spectroscopy. The obtained results indicated that enriched phenolic fractions of sweet cherries (cv. Saco, can impair cell viability and suppress cells growth after 72 h of exposure, promoting necrosis at the highest tested concentrations (>50 µg/mL). Additionally, fractions also showed the capacity to protect these cells against oxidative injury by capturing radicals before they can attack cells’ membrane and by modulating reactive oxygen and nitrogen species generation, as demonstrated by bioinformatic tools.

Highlights

  • Cancer is considered one of the most alarming medical problems worldwide

  • Considering the high liver cancer death rates and the lack of reports about the effect of sweet cherries on tumoral hepatic cell proliferation and cytotoxicity, the present study provides the first information about the pharmacological effects of sweet cherry concentrated phenolic-rich fractions

  • Fourier Transform Infrared (FT-IR) analysis is largely used for being simple to perform, economical, as well as due to their possibility to provide a molecular fingerprint of the sample by featuring their molecular vibrations, and allowing detailed analysis of the characteristics of the samples [41]

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Summary

Introduction

Cancer is considered one of the most alarming medical problems worldwide. This disease results from genetic and epigenetic alterations of oncogenes or tumour suppressor genes, leading to uncontrolled and rapid cells growth, proliferation and invasion to other organs and tissues [1]. Since several epidemiological and animal studies highlight that daily consumption of vegetables and fruits are robust and viable strategies useful to reduce the development and/or to act as a complementary treatment against various cancer types, being capable of increasing survival rates [7,8,9,10], it is not surprising the increasing incorporation of molecules derived from natural products in antitumor drugs [7] Among these molecules, phenolic compounds, such as phenolic acids, flavan-3-ols and anthocyanins, have been largely studied due to their antioxidant, anti-inflammatory and antimutagenic effects, as well as capacities to inhibit cell development and differentiation, modulate cell metabolism, induce cell cycle arrest and apoptosis, and control the expression of genes involved on cancer cells growth, among others [3,11,12,13,14]. The phenolic profile was characterized using the Fourier transform infrared (FT-IR) spectroscopy

Chemical Reagents
Cherry Samples
Preparation of Crude Cherry Extracts
Cancer Cell Models
MTT Reduction
Membrane Integrity Assay
Cells’ Morphology
2.10. Determination of NO Levels
2.12. Measurement of Intracellular Reactive Oxygen Species
2.13. Preparation of Protein and Ligands
2.14. Receptor-Ligand Docking
2.15. Inhibition of Lipid Peroxidation
2.16. Ferric Reducing-Antioxidant Power Assay
2.17. Statistical Analysis of Results
FT-IR Spectroscopy Analysis
Effect of Sweet Cherry Fractions in HepG2 Cell Viability
Cell Culture Radical Scavenging Activity
NO Scavenging Activity
Docking Results
Conclusions

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