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.
Highlights
Apple (Malus domestica), one of the most widely consumed edible fruits worldwide, is considered a major source of bioactive compounds such as phenolics, flavonoids, terpenoids, and carotenoids possessing various health benefits, such as providing a source of antioxidants in the diet and reduction of cancer risk in humans [1,2]
A total of eight polyphenolic compounds were quantified in apple pomace, as follows: chlorogenic acid (5.2 ± 0.082) epicatechin
Extensive studies have indicated that apple pomace consists of numerous types of polyphenolic compounds that are similar to those observed in apple fruit—including flavanols, flavones, flavanones, chalcones, hydroxycinnamic acids, and anthocyanins [17,18]
Summary
Apple (Malus domestica), one of the most widely consumed edible fruits worldwide, is considered a major source of bioactive compounds such as phenolics, flavonoids, terpenoids, and carotenoids possessing various health benefits, such as providing a source of antioxidants in the diet and reduction of cancer risk in humans [1,2]. Various techniques have been employed in the utilization of apple pomace for the direct extraction of various bioactive compounds—such as polyphenolics—possessing various biological properties. These have received much interest over the years as a natural and low-cost source of phytochemicals [2,4]. These phytochemicals play a significant role in maintaining human health by exercising preventive effects against cardiovascular diseases, diabetes, and cancer [1,5]. Chlorogenic acid, epicatechin, caffeic acid, coumaric acid, quercetin-3-glucoside (Q3G; isoquercetin), quercetin, phloridzin, and phloretin are the major polyphenolics found in apple pomace [7,8]
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