Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma

Cho, Jung Jae; Chae, Jung‐Il; Yoon, Goo; Kim, Ka Hwi; Cho, Jin Hyoung; Cho, Seung‐Sik; Cho, Young Sik; Shim, Jung‐Hyun

doi:10.3892/ijo.2014.2461

Cited by 64 publications

(48 citation statements)

References 46 publications

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“…A number of studies have reported that Sp1 is highly expressed in a variety of human tumors and that the use of natural compounds may be used to inhibit Sp1 expression in cancer (33). The effectiveness of anticancer agents is closely dependent on apoptosis induction.…”

Section: Discussionmentioning

confidence: 99%

“…Sp1 is a transcription factor that modulates cell cycle regulation, anti-proliferative, and apoptosis cell death by regulating the promoter of target genes (14,32). Moreover, Sp1 regulates expression of many proteins such as p21, p27, cyclin D1, Mcl-1 and survivin (33). Among a variety of genes involved, in this experiment, cyclin D1, Mcl-1 and survivin were investigated.…”

Section: Manu a Modulates Sp1 And Sp1-regulated Proteins In The Maligmentioning

confidence: 99%

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Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway

Kim

Chae

et al. 2016

Oncology Reports

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Abstract. Manumycin A (Manu A) is a natural product isolated from Streptomyces parvulus and has been reported to have anti-carcinogenic and anti-biotic properties. However, neither its molecular mechanism nor its molecular targets are well understood. Thus, the aim of the present study was to explore the possibility that Manu A has cancer preventive and chemotherapeutic effects on malignant pleural mesothelioma (MPM) through regulation of Sp1 and induction of mitochondrial cell death pathway. Manu A inhibited the cell viability of MSTO-211H and H28 cells in a concentration-dependent manner as determined by MTS assay. IC 50 values were calculated as 8.3 and 4.3 µM in the MSTO-311H and H28 cells following 48 h incubation, respectively. Manu A induced a significant increase in apoptotic indices as shown by DAPI staining, Annexin V assay, multi-caspase activity and mitochondrial membrane potential assay. The downregulation of Sp1 mRNA and protein expression by Manu A led to apoptosis by suppressing Sp1-regulated proteins (cyclin D1, Mcl-1 and survivin). Manu A decreased the protein levels of BID, Bcl-xL and PARP while it increased Bax levels. Manu A caused depolarization of the mitochondrial membrane with induction of CHOP, DR4 and DR5. Our results demonstrated that Manu A exerted anticancer effects by inducing apoptosis via inhibition of the Sp1-related signaling pathway in human MPM.

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Section: Discussionmentioning

confidence: 99%

Section: Manu a Modulates Sp1 And Sp1-regulated Proteins In The Maligmentioning

confidence: 99%

Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway

Kim

Chae

et al. 2016

Oncology Reports

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“…Previous studies on the development of chemotherapeutic agents have been focused on inducing cancer-specific cell death through the modulation of apoptosis, or programmed cell death. Furthermore, to overcome the side effects of current chemotherapeutic agents, studies have focused on the anti-cancer activity of natural compounds purified from herbal plants (7,(11)(12)(13)(14)(15). As a result of these studies, the US Food and Drug Administration approved the clinical use of a medicinal herbal plant-derived natural compound with anti-cancer activity for cancer therapy (16).…”

Section: Licochalcone-e Induces Caspase-dependent Death Of Human Pharmentioning

confidence: 99%

“…Licorice inhibits metastasis (18), has anti-proliferative properties (19), increases apoptosis and may cause cell cycle arrest (14). Recently, the authors demonstrated that licochalcone-A, a natural phenolic chalconoid purified from licorice (15), induces caspase-dependent apoptotic FaDu cell death through the extrinsic and intrinsic apoptotic signaling pathways.…”

Section: Licochalcone-e Induces Caspase-dependent Death Of Human Pharmentioning

confidence: 99%

Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways

Cho

Kang

et al. 2017

Oncology Letters

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Abstract. The aim of the present study was to investigate licochalcone-E (Lico-E)-induced apoptosis and the associated apoptotic signaling pathway in FaDu cells, a human pharyngeal squamous carcinoma cell line. Treatment with Lico-E exhibited significant cytotoxicity on FaDu cells in a concentration-dependent manner. The IC 50 value of Lico-E in FaDu cells was ~50 µM. Treatment with Lico-E increased the number of dead FaDu cells. Furthermore, chromatin condensation, which is associated with apoptotic cell death, was observed in FaDu cells treated with Lico-E for 24 h. By contrast, Lico-E did not produce cytotoxicity or increase the number of dead cells when applied to human normal oral keratinocytes (hNOKs). Furthermore, chromatin condensation was not observed in hNOKs treated with Lico-E. Treatment with Lico-E increased the expression of Fas ligand and the cleaved form of caspase-8 in FaDu cells. Furthermore, treatment with Lico-E increased the expression of pro-apoptotic factors, including apoptosis regulator BAX, Bcl-2-associated agonist of cell death, apoptotic protease-activating factor 1, caspase-9 and tumor suppressor p53, while decreasing the expression of anti-apoptotic factors, including apoptosis regulator Bcl-2 and Bcl-2-like protein 1 in FaDu cells. The expression of cleaved caspases-3 and poly (ADP-ribose) polymerase was significantly upregulated following treatment with Lico-E in FaDu cells, while Lico-E-induced apoptotic FaDu cell death was partially suppressed by treatment with Z-VAD-FMK, a pan caspase inhibitor. Therefore, Lico-E-induced oral cancer (OC) cell-specific apoptosis is mediated by the death receptor-dependent extrinsic and mitochondrial-dependent intrinsic apoptotic signaling pathways. In conclusion, these data suggested that Lico-E exhibits potential chemopreventive effects and warrants further developed as a chemotherapeutic agent against OC.

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“…Licochalcone A, an anti-inflammatory [1][2][3][4], immunomodulatory [5,6], and antimicrobial [3,5,[7][8][9] polyphenol extracted from Glycyrrhiza inflata [1][2][3]10], triggers apoptosis or inhibits proliferation and migration of tumor cells [11], including those of cervical cancer [12], oral squamous carcinoma [7,9,[13][14][15], esophageal carcinoma [16], gastric cancer [4,17,18], hepatocellular carcinoma [2,19], malignant pleural mesothelioma [20], bladder determined photometrically at 405 nm. The absorption of the supernatant of erythrocytes lysed in distilled water was defined as 100% hemolysis.…”

Section: Introductionmentioning

confidence: 99%

Licochalcone A Induced Suicidal Death of Human Erythrocytes

Egler

Läng

2015

Cell Physiol Biochem

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Background: The anti-inflammatory, immunomodulatory, and antimicrobial Glycyrrhiza inflata extract component licochalcone A triggers apoptosis of tumor cells and is thus considered for the treatment of malignancy. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling involved in the triggering of eryptosis includes Ca²⁺ entry with increase of cytosolic Ca²⁺ activity ([Ca²⁺]_i), and ceramide. The present study explored, whether and how licochalcone A induces eryptosis. Methods: Human erythrocytes drawn from healthy individuals were exposed for 24 hours to 1-10 µg/ml licochalcone A. Flow cytometry was subsequently employed to estimate phosphatidylserine exposure at the cell surface from annexin V binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, and ceramide utilizing specific antibodies. In addition, hemolysis was quantified from hemoglobin release. Results: Licochalcone A significantly increased the percentage of annexin-V-binding cells (≥ 5 µg/ml), significantly decreased forward scatter (2.5 - 5 µg/ml), significantly increased Fluo3-fluorescence (≥ 7.5 µg/ml), and significantly increased ceramide abundance (10 µg/ml). The effect of licochalcone on annexin-V-binding was not significantly modified, but hemolysis significantly enhanced by removal of extracellular Ca²⁺. Conclusions: Licochalcone triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect independent from Ca²⁺ entry and presumably in part due to ceramide.

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Licochalcone A, a natural chalconoid isolated from Glycyrrhiza inflata root, induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma

Cited by 64 publications

References 46 publications

Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway

Manumycin A induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway

Licochalcone-E induces caspase-dependent death of human pharyngeal squamous carcinoma cells through the extrinsic and intrinsic apoptotic signaling pathways

Licochalcone A Induced Suicidal Death of Human Erythrocytes

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