Role of limonin in anticancer effects of Evodia rutaecarpa on ovarian cancer cells

Bae, Jae Ryul; Park, Wook Ha; Suh, Dong Hoon; No, Jae Hong; Kim, Yong Beom; Kim, Kidong

doi:10.1186/s12906-020-02890-y

Cited by 17 publications

(11 citation statements)

References 41 publications

(53 reference statements)

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“…It is a secondary metabolite that is widely found in citrus fruits [ 7 ]. Numerous studies have shown that limonin exhibits a wide spectrum of biological and pharmacological activities, including anti-cancer [ 8 , 9 , 10 ], anti-inflammatory [ 10 , 11 ], anti-oxidative [ 12 ], anti-viral [ 13 ], and liver-protective properties [ 14 , 15 ]. Hesperidin, or vitamin P, is a flavanone glycoside found in all types of citrus fruits.…”

Section: Introductionmentioning

confidence: 99%

A Green Extraction Method to Achieve the Highest Yield of Limonin and Hesperidin from Lime Peel Powder (Citrus aurantifolia)

2022

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Green extraction is aimed at reducing energy consumption by using renewable plant sources and environmentally friendly bio-solvents. Lime (Citrus aurantifolia) is a rich source of flavonoids (e.g., hesperidin) and limonoids (e.g., limonin). Manufacturing of lime products (e.g., lime juice) yields a considerable amount of lime peel as food waste that should be comprehensively exploited. The aim of this study was to develop a green and simple extraction method to acquire the highest yield of both limonin and hesperidin from the lime peel. The study method included ethanolic-aqueous extraction and variable factors, i.e., ethanol concentrations, pH values of solvent, and extraction temperature. The response surface methodology was used to optimize extraction conditions. The concentrations of limonin and hesperidin were determined by using UHPLC-MS/MS. Results showed that the yields of limonin and hesperidin significantly depended on ethanol concentrations and extraction temperature, while pH value had the least effect. The optimal extraction condition with the highest amounts of limonin and hesperidin was 80% ethanol at pH 7, 50 °C, which yields 2.072 and 3.353 mg/g of limonin and hesperidin, respectively. This study illustrates a green extraction process using food waste, e.g., lime peel, as an energy-saving source and ethanol as a bio-solvent to achieve the highest amount of double bioactive compounds.

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Section: Introductionmentioning

confidence: 99%

A Green Extraction Method to Achieve the Highest Yield of Limonin and Hesperidin from Lime Peel Powder (Citrus aurantifolia)

2022

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“…Previous studies have suggested that several active Evodia compounds exert cytotoxic effects on human cancer cell lines. Speci cally, evodiamine has an inhibitory effect on human lung cancer A549 cells [32], and limonin in Evodia induces apoptosis in ovarian cancer cells by activating the p53 signaling pathway [33]. Additionally, evodiamine plays an important role in activating JNK and PERK in human ovarian cancer cells to induce apoptosis [34] and inhibits the proliferation of hepatocarcinoma cells through a WWOX-dependent pathway to induce anticancer activity [35].…”

Section: Discussionmentioning

confidence: 99%

Analysis and verification of the molecular mechanism of Evodia in the treatment of nasopharyngeal carcinoma using network pharmacology and molecular docking

Yang

et al. 2022

Preprint

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Background: Nasopharyngeal carcinoma (NPC) is a neoplasm of the head and neck, with the highest incidence and mortality rates occurring in East and Southeast Asia. Evodia rutaecarpa is a tree that is native to Korea and China, and its fruit (hereafter referred to as Evodia) exhibits remarkable antitumor properties. However, little is known about its mechanism of action in NPC. In this study, we employed network pharmacology to identify targets of the active Evodia compounds in nasopharyngeal carcinoma and generate an interaction network.Methods: The active ingredients of Evodia and the targets for nasopharyngeal carcinoma were obtained from multiple databases, and an interaction network was constructed via the Cytoscape and STRING databases. The key biological processes and signaling pathways were predicted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Molecular docking technology was used to identify the affinity and activity of target genes, while The Cancer Genome Atlas and Human Protein Atlas databases were used to analyze differential expression. Cell Counting Kit (CCK)-8 and Annexin V-FITC/PI dual fluorescence staining were used for experimental verification.Results: Active Evodia compounds included quercetin, isorhamnetin, and evodiamine, and important nasopharyngeal carcinoma targets included MAPK14, AKT1, RELA, MAPK1, JUN, and p53, whose content in the lipid and atherosclerosis signaling pathways was also high. Additionally, we verified the high affinity and activity of the active compounds through molecular docking, and the target proteins were verified using immunohistochemistry and differential expression analyses. Furthermore, Cell Counting Kit-8 assays and Annexin V-FITC/propidium iodide dual-fluorescence staining verified that isorhamnetin inhibited the proliferation of nasopharyngeal carcinoma cells and induced apoptosis, respectively.Conclusion: These results elucidated the molecular mechanism of Evodia and demonstrated its ability to alter the proliferation and apoptosis of nasopharyngeal carcinoma cells through multiple targets and pathways, thereby providing evidence for its clinical application.

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“…For example, Bae et al. (2020) found that limonin can induce cell apoptosis by activating p53 signal pathway, reducing the viability of SKOV‐3, A2780, and RMUG‐S ovarian cancer cells, and reversing the drug resistance of CISRSKOV‐3 cells by activating apoptosis. Gong et al (2019) found that limonin can effectively inhibit lung cancer induced by benzopyrene (BP) in mice, and in vitro experiments showed that limonin can promote the production of reactive oxygen species (ROS) and induce apoptosis of A549 lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

Chen

Liang

et al. 2021

Food Science & Nutrition

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Limonin is an important bioactive substance in citrus fruits, especially in seeds, which has great potential in cancer prevention and treatment. In order to explore the anticancer activity based on interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL‐60) were studied in vitro. We found that limonin could inhibit proliferation and promote apoptosis of HL‐60 cells, and the effect was positively correlated with its dosage. Western blot results showed that limonin could activate the endogenous apoptosis pathway mediated by mitochondria via up‐regulating pro‐apoptotic proteins (Bax, cytochrome c, Caspase3, and Caspase9) and down‐regulating anti‐apoptotic proteins (Bcl‐2), thus inhibiting the proliferation of HL‐60 cells and promoting apoptosis, which further proved the anticancer activity of limonin from the molecular mechanism. At the same time, limonin down‐regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes.

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Role of limonin in anticancer effects of Evodia rutaecarpa on ovarian cancer cells

Cited by 17 publications

References 41 publications

A Green Extraction Method to Achieve the Highest Yield of Limonin and Hesperidin from Lime Peel Powder (Citrus aurantifolia)

A Green Extraction Method to Achieve the Highest Yield of Limonin and Hesperidin from Lime Peel Powder (Citrus aurantifolia)

Analysis and verification of the molecular mechanism of Evodia in the treatment of nasopharyngeal carcinoma using network pharmacology and molecular docking

Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

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