Characterization and Purification of Bergamottin from Citrus grandis (L.) Osbeck cv. Yongjiazaoxiangyou and Its Antiproliferative Activity and Effect on Glucose Consumption in HepG2 cells

Liu, Yilong; Ren, Chao; Cao, Yunlin; Wang, Yue; Duan, Wenyi; Xie, Linfeng; Sun, Chongde; Li, Xian

doi:10.3390/molecules22071227

Cited by 29 publications

(15 citation statements)

References 38 publications

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“…The anti-proliferative activity of bergamottin against promyelocytic leukemia HL-60 cells has also previously been reported by our group [58,59]. We observed that the combination of bergamottin and simvastatin produced synergistic effects on the tumor necrosis factor (TNF)-induced cytotoxicity and apoptosis in human chronic myelogenous leukemia KBM-5 cells.…”

Section: Bergamottin and Cancersupporting

confidence: 79%

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Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy

Arfuso

Sethi

et al. 2018

IJMS

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Cancer still remains one of the leading causes of death worldwide. In spite of significant advances in treatment options and the advent of novel targeted therapies, there still remains an unmet need for the identification of novel pharmacological agents for cancer therapy. This has led to several studies evaluating the possible application of natural agents found in vegetables, fruits, or plant-derived products that may be useful for cancer treatment. Bergamottin is a furanocoumarin derived from grapefruits and is also a well-known cytochrome P450 inhibitor. Recent studies have demonstrated potent anti-oxidative, anti-inflammatory, and anti-cancer properties of grapefruit furanocoumarin both in vitro and in vivo. The present review focuses on the potential anti-neoplastic effects of bergamottin in different tumor models and briefly describes the molecular targets affected by this agent.

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Section: Bergamottin and Cancersupporting

confidence: 79%

“…The anti-proliferative activity of bergamottin against human liver cancer HepG2 cells and gastric cancer BGC-823 cells has also been reported [59]. The cytotoxic effect of bergamottin on gastric cancer NCI-N87 cells has also been reported [65].…”

Section: Bergamottin and Cancermentioning

confidence: 99%

Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy

Arfuso

Sethi

et al. 2018

IJMS

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“…As far as we know, this is the first report about the anticancer activity of bergamottin toward HeLa cells. As shown in previous reports, although BM showed an inhibition effect on many cancer cell lines, such as HT-1080 fibrosarcoma [17], U266 multiple myeloma [18], HepG2 liver cancer, BGC-823 gastric cancer, HL-60 promyelotic leukemia [38], and A549 lung cancer cells [16], we did not observe BM to be significantly cytotoxic toward the HeLa cell line. Nevertheless, the insertion of a nitroxide moiety (10, IC 50.…”

Section: Discussionsupporting

confidence: 71%

Synthesis of Spin-Labelled Bergamottin: A Potent CYP3A4 Inhibitor with Antiproliferative Activity

Zsidó

Balog

Erős

et al. 2020

IJMS

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Bergamottin (BM, 1), a component of grapefruit juice, acts as an inhibitor of some isoforms of the cytochrome P450 (CYP) enzyme, particularly CYP3A4. Herein, a new bergamottin containing a nitroxide moiety (SL-bergamottin, SL-BM, 10) was synthesized; chemically characterized, evaluated as a potential inhibitor of the CYP2C19, CYP3A4, and CYP2C9 enzymes; and compared to BM and known inhibitors such as ketoconazole (KET) (3A4), warfarin (WAR) (2C9), and ticlopidine (TIC) (2C19). The antitumor activity of the new SL-bergamottin was also investigated. Among the compounds studied, BM showed the strongest inhibition of the CYP2C9 and 2C19 enzymes. SL-BM is a more potent inhibitor of CYP3A4 than the parent compound; this finding was also supported by docking studies, suggesting that the binding positions of BM and SL-BM to the active site of CYP3A4 are very similar, but that SL-BM had a better ∆Gbind value than that of BM. The nitroxide moiety markedly increased the antitumor activity of BM toward HeLa cells and marginally increased its toxicity toward a normal cell line. In conclusion, modification of the geranyl sidechain of BM can result in new CYP3A4 enzyme inhibitors with strong antitumor effects.

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“…HSCCC (TBE-300A, Shanghai Tauto Biotech. Co., Ltd., Shanghai, China) was used for further purification of nobiletin, tangeretin, and 5-demethylnobiletin from the PMF fraction according to our previous publication [21] with some modifications. Partition coefficients ( K value) of the three PMF monomers in different ratios of solutions were calculated, and the K value was used for selecting the two-phase solvent system.…”

Section: Methodsmentioning

confidence: 99%

Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway

Wang

Zang

et al. 2019

Nutrients

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In order to establish an efficient method for separation of polymethoxyflavones (PMFs) and explore the anti-inflammatory mechanism of PMF monomers, a citrus variety rich in PMFs, Ougan (Citrus reticulata cv. Suavissima), was selected, and three monomers, including nobiletin, tangeretin, and 5-demethylnobiletin, were purified by ultrasonic-assisted extraction, solid phase extraction, and high-speed countercurrent chromatography separation. UPLC-MS was used to identify the three monomers. UPLC determined purities of 99.87% to nobiletin, 99.76% to tangeretin, and 98.75% to 5-demethylnobiletin with the standard curve method. A lipopolysaccharide (LPS)-induced NO releasing model was performed in the mouse microglia BV-2 cell line. Results illustrated that PMF monomers inhibited the NO release and the inflammation-related cytokines, including IL-1β, IL-6, and TNFα elevation. QRT-PCR revealed that PMFs alleviated LPS-induced upregulation of iNOS, IL-6, JAK2, TNFα, IL-1β, and NF-κB and LPS-induced downregulation of IκBα, while they did not affect TLR1, TLR2, TLR4, and TLR6. STAT3 expression was repressed by tangeretin and 5-demethylnobiletin, but not by nobiletin. Western blot assay also showed a suppression of expression and phosphorylation of JAK2 by all three PMF monomers, while STAT3 phosphorylation was restrained by tangeretin and 5-demethylnobiletin. The mechanism was primarily verified by the JAK2 inhibitor Ruxolitinib and the STAT3 inhibitor Stattic.

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Characterization and Purification of Bergamottin from Citrus grandis (L.) Osbeck cv. Yongjiazaoxiangyou and Its Antiproliferative Activity and Effect on Glucose Consumption in HepG2 cells

Cited by 29 publications

References 38 publications

Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy

Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy

Synthesis of Spin-Labelled Bergamottin: A Potent CYP3A4 Inhibitor with Antiproliferative Activity

Three Polymethoxyflavones Purified from Ougan (Citrus reticulata Cv. Suavissima) Inhibited LPS-Induced NO Elevation in the Neuroglia BV-2 Cell Line via the JAK2/STAT3 Pathway

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