Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels

Abstract

Cervical cancer is a life-threatening disease and the fourth most common cancer among women worldwide. Apple pomace is a multifunctional phenolic compound possessing effective biological activity against cervical cancer cells. This study aimed to investigate the anticancer effects of quercetin-3-glucoside (Q3G) extracted from apple pomace in HeLa cell lines and analyze its molecular mechanisms. High-performance liquid chromatography revealed that Q3G, coumaric acid, phloridzin, quercetin, and phloretin are the major polyphenolic compounds constituting apple pomace. Among them, Q3G possessed the greatest antioxidant and anti-inflammatory effects in vitro and exhibited significant cytotoxic effects in HeLa cells in a dose-and time-dependent manner. Flow cytometric analysis indicated that Q3G induced cell cycle arrest at the S phase in a time-dependent manner by altering cyclin-dependent kinase 2. Moreover, it induced apoptosis via chromosomal DNA degradation and increased reactive oxygen species generation. Furthermore, Q3G treatment altered the apoptosis-associated protein expression in the cells by activating caspase-9/-3, downregulating anti-apoptosis protein B-cell lymphoma (Bcl)-2 expressions and up regulating the pro-apoptotic Bcl-2-associated X protein. BH3-interacting domain death agonist cleavage occurred prior to the degradation of an anti-apoptotic Mu-2-related death-inducing gene involved in cell death signaling. Consequently, apple pomace Q3G holds promise as an anti-inflammatory and anticancer agent for treating cervical cancer.

Green Synthesis of Silver Nanoparticles Using the Tridax procumbens Plant Extract and Screening of Its Antimicrobial and Anticancer Activities

“…Limitations in cancer treatment are a result of the challenges seen in cancer therapies today, including lack of early diagnosis, nonspecific systemic distribution, inadequate drug concentrations reaching the tumor, and inability to monitor therapeutic responses. The cause of significant complications, such as multidrug resistance, is poor drug delivery and its residence at the target site [ 3 , 4 ]. Nanotechnology has the potential to offer solutions to these current obstacles in cancer therapies as well as solutions to develop resistance to antibiotics in microbes [ 5 , 6 ].…”

Chemical Composition, Antioxidant Activity and Cytocompatibility of Polyphenolic Compounds Extracted from Food Industry Apple Waste: Potential in Biomedical Application

“…The differences in % D IA observed among ethanolic extract of AP fractions in this study can be associated with different distributions of polyphenolic compounds with different concentrations, their chemical composition, and the degree of possible oxidation [ 32 ]. The higher % D IA of the peel extract (fraction B) compared to other fractions could be due to the existence of a higher concentration of polyphenolic compounds including quercetin and quercetin glycosides, which are more potent in radical scavenging activity than some other polyphenols such as chlorogenic acid and phloridzin, which were detected in high concentration in seed and core extracts (fraction C) [ 49 , 50 , 51 ].…”

“…Higher DPPH radical inhibition activity (14.96 ± 2.36 mM Trolox equivalents kg −1 fw), more than two-fold, was found in the extract of organic peel compared to the pulp extract (6.28 ± 2.72 mM Trolox equivalents kg −1 fw), which was attributed to the presence of a higher concentration of polyphenols such as flavanols (catechin and epicatechin), quercetin glycosides, and procyanidins with higher capacities compared to hydroxycinnamates (chlorogenic acid) and dihydrochalcones (phloridzin) with lower potential in DPPH radical inhibition activity [ 49 ]. Nile et al found that quercetin-3-glucoside extracted from AP displayed the highest % D IA (90.75%), compared to other polyphenols such as chlorogenic acid, coumaric acid, epicatechin, and phloridzin [ 51 ].…”

“…Considering our results, it can be found that the composition and content of polyphenols are different among various studied AP samples. These changes can be attributed to the variation in apple variety, manufacturing procedures, a fraction (part) of AP used as well as different extraction techniques for polyphenol extraction [ 51 , 61 ]. Fraction C contained the highest total concentration of polyphenols compared to other fractions in terms of selected polyphenols for detection; however, as the HPLC chromatograms exhibited, other different polyphenolic compounds were present in the polyphenolic extract of the fractions, particularly in fraction B, which were not among the main polyphenols quantified in this research.…”

Secondary Metabolites with Biomedical Applications from Plants of the Sarraceniaceae Family

“…Isoquercetrin exhibits significant cytotoxic action on human cervical cancer cells (HeLa) in a dose- and time-dependent manner with potent antioxidant as well as anti-inflammatory effects. Proliferation is inhibited via cell cycle arrest and apoptosis through increased generation of ROS, disruption of cellular homeostasis which eventually leads to DNA damage and cell death [ 134 ]. Quercetin-3-O-glucoside has a more potent antiproliferative effect than quercetin and quercetin-3-O-rutinoside (rutin) [ 135 ].…”