Isoliquiritigenin

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Jing Yang - One of the best experts on this subject based on the ideXlab platform.

  • Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of pi3k akt in human breast cancer
    Toxicology and Applied Pharmacology, 2013
    Co-Authors: Ying Li, Hongyan Chai, Haixia Zhao, Yuzhong Wang, Hao Zheng, Wei Yu, Jing Zhang, John R Falck, Renxiu Peng, Jing Yang
    Abstract:

    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that Isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, Isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E2 (PGE2) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B4 (LTB4). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser241), phospho-Akt (Thr308), phospho-Bad (Ser136), and Bcl-xL expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE2, LTB4 and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed Isoliquiritigenin-induced apoptosis. Notably, Isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr308). Collectively, these data suggest that Isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic network and the deactivation of PI3K/Akt in human breast cancer.

  • Analgesic and Uterine Relaxant Effects of Isoliquiritigenin, a Flavone from Glycyrrhiza glabra
    Phytotherapy research : PTR, 2012
    Co-Authors: Yulu Shi, Jing Yang, Zhen Sun, Hongyan Chai, Li Tang, Yue Guo
    Abstract:

    Shaoyao-gancao-tang, a Chinese medicinal formula consisting of peony and licorice has been used for the treatment of dysmenorrhea for thousands of years. The purpose of the present study was to demonstrate the analgesic and uterine relaxant effects of Isoliquiritigenin (ISL), a flavonoid isolated from the roots of Glycyrrhiza glabra (a type of licorice). In vitro, Isoliquiritigenin caused concentration-dependent inhibition of spontaneous contraction of isolated rat uterus and the contraction induced by various types of stimulants, such as acetylcholine (Ach, 10 mM), KCl (40 mM) and oxytocin (1 mU/mL). The uterine contractile response to cumulative concentrations of CaCl₂ was blocked by 0.1 and 1 mM of Isoliquiritigenin. The Isoliquiritigenin-induced relaxation was partly inhibited by the nitric oxide synthase (NOS) inhibitor Nv-nitro-L-arginine methylester (L-NAME, 100 mM) and the COX-1/COX-2 inhibitor indomethacin (10mM). In vivo, Isoliquiritigenin could cause a significant reduction in the acetic acid-induced writhing response and hot-plate test at the high dose. These results indicate that Isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra, not only has a spasmolytic effect on uterine contraction, which is in relation to Ca²⁺ channels, NOS and COX, but also an effective activity in reducing pain.

  • Isoliquiritigenin a flavonoid from licorice plays a dual role in regulating gastrointestinal motility in vitro and in vivo
    Phytotherapy Research, 2009
    Co-Authors: Gang Chen, Yang Liu, Lingxin Zhu, Qian Zhou, Hao Chen, Jing Yang
    Abstract:

    Licorice root has been used for years to regulate gastrointestinal function in traditional Chinese medicine. This study reveals the gastrointestinal effects of Isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra (a kind of Licorice). In vivo, Isoliquiritigenin produced a dual dose-related effect on the charcoal meal travel, inhibitory at the low doses, while prokinetic at the high doses. In vitro, Isoliquiritigenin showed an atropine-sensitive concentration-dependent spasmogenic effect in isolated rat stomach fundus. However, a spasmolytic effect was observed in isolated rabbit jejunums, guinea pig ileums and atropinized rat stomach fundus, either as noncompetitive inhibition of agonist concentration-response curves, inhibition of high K(+) (80 mM)-induced contractions, or displacement of Ca(2+) concentration-response curves to the right, indicating a calcium antagonist effect. Pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME; 30 microM), indomethacin (10 microM), methylene blue (10 microM), tetraethylammonium chloride (0.5 mM), glibenclamide (1 microM), 4-aminopyridine (0.1 mM), or clotrimazole (1 microM) did not inhibit the spasmolytic effect. These results indicate that Isoliquiritigenin plays a dual role in regulating gastrointestinal motility, both spasmogenic and spasmolytic. The spasmogenic effect may involve the activating of muscarinic receptors, while the spasmolytic effect is predominantly due to blockade of the calcium channels.

  • Isoliquiritigenin a flavonoid from licorice relaxes guinea pig tracheal smooth muscle in vitro and in vivo role of cgmp pkg pathway
    European Journal of Pharmacology, 2008
    Co-Authors: Bin Liu, Jing Yang, Qingshan Wen
    Abstract:

    Licorice root is used to treat asthma as a component of Shaoyao-Gancao-tang, a traditional Chinese medicine formula. In this study, we investigated the tracheal relaxation effects of Isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra (a kind of Licorice), on guinea-pig tracheal smooth muscle in vitro and in vivo. The tension changes of isolated tracheal rings were isometrically recorded on a polygraph. The large-conductance Ca2+-activated K+ channels (BKCa) were measured by inside-out patch-clamp techniques and intracellular Ca2+concentrations ([Ca2+]i) were tested by microfluorometric method in guinea-pig tracheal smooth muscle cells (TSMCs). Isoliquiritigenin produced concentration-dependent relaxation in isolated guinea-pig tracheal rings precontracted with acetylcholine, KCl, and histamine. Pretreatments with charybdotoxin, ODQ and KT5823 attenuated the relaxation induced by Isoliquiritigenin. Isoliquiritigenin significantly increased intracellular cGMP level in cultured TSMCs and inhibited the activity of phosphodiesterase (PDE) 5 in human platelets. Moreover, Isoliquiritigenin increased by 9-fold the probability of BKCa channel openings of TSMCs in inside-out patches and markedly reduced [Ca2+]i rise induced by acetylcholine inTSMCs, pretreatment with KT5823 attenuated above two responses to Isoliquiritigenin. In vivo experiment Isoliquiritigenin significantly prolonged the latency time of histamine-acetylcholine aerosol-induced collapse and inhibited the increase of lung overflow induced by intravenously administered histamine dose-dependently. These data indicate that Isoliquiritigenin relaxes guinea-pig trachea through a multiple of intracellular actions, including sGC activation, inhibition of PDEs, and associated activation of the cGMP/PKG signaling cascade, leading to the opening of BKCa channels and [Ca2+]i decrease through PKG-dependent mechanism and thus to tracheal relaxation.

  • Isoliquiritigenin, a flavonoid from licorice, relaxes guinea-pig tracheal smooth muscle in vitro and in vivo: role of cGMP/PKG pathway.
    European journal of pharmacology, 2008
    Co-Authors: Bin Liu, Jing Yang, Qingshan Wen
    Abstract:

    Licorice root is used to treat asthma as a component of Shaoyao-Gancao-tang, a traditional Chinese medicine formula. In this study, we investigated the tracheal relaxation effects of Isoliquiritigenin, a flavonoid isolated from the roots of Glycyrrhiza glabra (a kind of Licorice), on guinea-pig tracheal smooth muscle in vitro and in vivo. The tension changes of isolated tracheal rings were isometrically recorded on a polygraph. The large-conductance Ca2+-activated K+ channels (BKCa) were measured by inside-out patch-clamp techniques and intracellular Ca2+concentrations ([Ca2+]i) were tested by microfluorometric method in guinea-pig tracheal smooth muscle cells (TSMCs). Isoliquiritigenin produced concentration-dependent relaxation in isolated guinea-pig tracheal rings precontracted with acetylcholine, KCl, and histamine. Pretreatments with charybdotoxin, ODQ and KT5823 attenuated the relaxation induced by Isoliquiritigenin. Isoliquiritigenin significantly increased intracellular cGMP level in cultured TSMCs and inhibited the activity of phosphodiesterase (PDE) 5 in human platelets. Moreover, Isoliquiritigenin increased by 9-fold the probability of BKCa channel openings of TSMCs in inside-out patches and markedly reduced [Ca2+]i rise induced by acetylcholine inTSMCs, pretreatment with KT5823 attenuated above two responses to Isoliquiritigenin. In vivo experiment Isoliquiritigenin significantly prolonged the latency time of histamine-acetylcholine aerosol-induced collapse and inhibited the increase of lung overflow induced by intravenously administered histamine dose-dependently. These data indicate that Isoliquiritigenin relaxes guinea-pig trachea through a multiple of intracellular actions, including sGC activation, inhibition of PDEs, and associated activation of the cGMP/PKG signaling cascade, leading to the opening of BKCa channels and [Ca2+]i decrease through PKG-dependent mechanism and thus to tracheal relaxation.

Fu Peng - One of the best experts on this subject based on the ideXlab platform.

  • Isoliquiritigenin modulates miR-374a/PTEN/Akt axis to suppress breast cancer tumorigenesis and metastasis
    Scientific reports, 2017
    Co-Authors: Fu Peng, Hailin Tang, Peng Liu, Jiangang Shen, Xin Yuan Guan, Xiaofang Xie, Jihai Gao, Liang Xiong, Lei Jia, Jianping Chen
    Abstract:

    Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that Isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of Isoliquiritigenin were explored. The results proved that Isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of Isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by Isoliquiritigenin treatment in breast cancer. Further study displayed that Isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest Isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies.

  • Isoliquiritigenin modulates mir 374a pten akt axis to suppress breast cancer tumorigenesis and metastasis
    Scientific Reports, 2017
    Co-Authors: Fu Peng, Hailin Tang, Peng Liu, Jiangang Shen, Xin Yuan Guan, Xiaofang Xie
    Abstract:

    Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that Isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of Isoliquiritigenin were explored. The results proved that Isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of Isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by Isoliquiritigenin treatment in breast cancer. Further study displayed that Isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest Isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies.

  • Cytotoxic Evaluation against Breast Cancer Cells of Isoliquiritigenin Analogues from Spatholobus suberectus and Their Synthetic Derivatives.
    Journal of natural products, 2015
    Co-Authors: Fu Peng, Jianping Chen, Chun-wang Meng, Qin-mei Zhou, Liang Xiong
    Abstract:

    Five Isoliquiritigenin analogues, including a new methylene-bridged bischalcone (1), were isolated from Spatholobus suberectus. Cytotoxicity screening of these isolates and several synthetic derivatives indicated that the introduction, removal, position modification, or glycosylation of hydroxy groups in Isoliquiritigenin did not improve the resultant cytotoxicity against the MCF-7 and MDA-MB-231 human breast cancer cell lines. In addition, cyclization of OH-2' chalcones or reduction of the α,β-unsaturated carbonyl double bond decreased such cytotoxicity substantially. However, methylation of hydroxy groups resulted in a marked increase in such cytotoxic activity. Among these active Isoliquiritigenin analogues, 3',4',5',4″-tetramethoxychalcone (3h) was obtained as a compound with promising cytotoxic activity.

Da-lei Zhang - One of the best experts on this subject based on the ideXlab platform.

Xiaofang Xie - One of the best experts on this subject based on the ideXlab platform.

  • Isoliquiritigenin modulates miR-374a/PTEN/Akt axis to suppress breast cancer tumorigenesis and metastasis
    Scientific reports, 2017
    Co-Authors: Fu Peng, Hailin Tang, Peng Liu, Jiangang Shen, Xin Yuan Guan, Xiaofang Xie, Jihai Gao, Liang Xiong, Lei Jia, Jianping Chen
    Abstract:

    Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that Isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of Isoliquiritigenin were explored. The results proved that Isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of Isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by Isoliquiritigenin treatment in breast cancer. Further study displayed that Isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest Isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies.

  • Isoliquiritigenin modulates mir 374a pten akt axis to suppress breast cancer tumorigenesis and metastasis
    Scientific Reports, 2017
    Co-Authors: Fu Peng, Hailin Tang, Peng Liu, Jiangang Shen, Xin Yuan Guan, Xiaofang Xie
    Abstract:

    Breast cancer is one of the most frightful causes of death among females worldwide. Accumulating evidence attached the importance of microRNAs negative regulation to tumorigenesis in breast cancer, suggesting novel cancer therapies targeting microRNAs modulation. Recent studies demonstrated that Isoliquiritigenin could inhibit breast cancer cells proliferation and migration, but the underlying mechanism is still limited. In this study, the anti-cancer effects as well as the detailed mechanisms of Isoliquiritigenin were explored. The results proved that Isoliquiritigenin could negatively regulate breast cancer growth through the induction of apoptosis. We also verified the anti-cancer effect of Isoliquiritigenin on migration and invasion, and identified highly expressed miR-374a as one of the main microRNAs down-regulated by Isoliquiritigenin treatment in breast cancer. Further study displayed that Isoliquiritigenin increased PTEN expression through the decrease of miR-374a expression to inhibit the aberrant Akt signaling. Our findings suggest Isoliquiritigenin as a novel anti-cancer candidate significantly regulating miR-374a/PTEN/Akt axis in microRNA-based breast cancer therapies.

Hoyoku Nishino - One of the best experts on this subject based on the ideXlab platform.

  • Induction of cell cycle arrest and p21CIP1/WAF1 expression in human lung cancer cells by Isoliquiritigenin
    Cancer letters, 2004
    Co-Authors: Tsunehiro, Yoshiko Satomi, Masaki Baba, Toru Okuyama, Hoyoku Nishino, Daishiro Katoh, Junichi Shimada, Nobuo Kitamura
    Abstract:

    Isoliquiritigenin is a natural flavonoid isolated from licorice, shallot and bean sprouts. The effect of Isoliquiritigenin on cell proliferation and cell cycle progression was examined in the A549 human lung cancer cell line. Isoliquiritigenin significantly inhibited the proliferation of lung cancer cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that Isoliquiritigenin restrained the cell cycle progression at G2/M phase. Further examinations using cDNA arrays and real-time quantitative RT-PCR revealed that Isoliquiritigenin enhanced the expression of p21CIP1/WAF1, a universal inhibitor of cyclin-dependent kinases. These results suggest that Isoliquiritigenin will be a promising agent for use in chemopreventive or therapeutics against lung cancer.

  • induction of cell cycle arrest and p21cip1 waf1 expression in human lung cancer cells by Isoliquiritigenin
    Cancer Letters, 2004
    Co-Authors: Yoshiko Satomi, Masaki Baba, Toru Okuyama, Hoyoku Nishino, Daishiro Katoh, Junichi Shimada, Nobuo Kitamura
    Abstract:

    Isoliquiritigenin is a natural flavonoid isolated from licorice, shallot and bean sprouts. The effect of Isoliquiritigenin on cell proliferation and cell cycle progression was examined in the A549 human lung cancer cell line. Isoliquiritigenin significantly inhibited the proliferation of lung cancer cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that Isoliquiritigenin restrained the cell cycle progression at G2/M phase. Further examinations using cDNA arrays and real-time quantitative RT-PCR revealed that Isoliquiritigenin enhanced the expression of p21CIP1/WAF1, a universal inhibitor of cyclin-dependent kinases. These results suggest that Isoliquiritigenin will be a promising agent for use in chemopreventive or therapeutics against lung cancer.

  • Isoliquiritigenin inhibits the growth of prostate cancer.
    European urology, 2003
    Co-Authors: Motohiro Kanazawa, Yoshiko Satomi, Yoichi Mizutani, Osamu Ukimura, Akihiro Kawauchi, Toshiyuki Sakai, Masaki Baba, Toru Okuyama, Hoyoku Nishino, Tsuneharu Miki
    Abstract:

    Abstract Objective: Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L. , is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. In this study, we investigated the anti-tumor effect of Isoliquiritigenin on prostate cancer in vitro. Methods: DU145 and LNCaP prostate cancer cell lines were used as targets. We examined the effects of Isoliquiritigenin on cell proliferation, cell cycle regulation and cell cycle-regulating gene expression. Further, we investigated the effects of Isoliquiritigenin on the GADD153 mRNA and protein expression, and promoter activity. Results: Isoliquiritigenin significantly inhibited the proliferation of prostate cancer cell lines in a dose-dependent and time-dependent manner. Fluorescence-activated cell sorting (FACS) analysis indicated that Isoliquiritigenin induced S and G2/M phase arrest. Isoliquiritigenin enhanced the expression of GADD153 mRNA and protein associated with cell cycle arrest. Further, Isoliquiritigenin stimulated transcriptional activity of GADD153 promoter dose-dependently. Conclusion: These findings suggest that Isoliquiritigenin is a candidate agent for the treatment of prostate cancer and GADD153 may play an important role in Isoliquiritigenin-induced cell cycle arrest and cell growth inhibition.

  • Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma
    Cancer letters, 2002
    Co-Authors: Shoji Yamazaki, Masaki Baba, Toru Okuyama, Tatuo Morita, Hitoshi Endo, Toshiro Hamamoto, Yoshiko Joichi, Sanae Kaneko, Yoshihito Okada, Hoyoku Nishino
    Abstract:

    Isoliquiritigenin is a chalcone isolated from licorice and shallots. The ability of Isoliquiritigenin to suppress metastasis was examined in a pulmonary metastasis model of mouse renal cell carcinoma. Isoliquiritigenin significantly reduced pulmonary metastasis, without any weight loss or leukocytopenia. Isoliquiritigenin suppressed in vitro proliferation of carcinoma cells, potentiated nitric oxide production by lipopolysaccharide-stimulated macrophages, and facilitated cytotoxicity of splenic lymphocytes in vitro. These findings suggest activation of macrophages, activation of cytotoxicity of lymphocytes, and direct cytotoxicity as possible mechanisms of metastasis suppression by Isoliquiritigenin. In addition, Isoliquiritigenin prevented severe leukocytopenia caused by administration of 5-fluorouracil.

  • studies on cancer chemoprevention by traditional folk medicines xxv inhibitory effect of Isoliquiritigenin on azoxymethane induced murine colon aberrant crypt focus formation and carcinogenesis
    Biological & Pharmaceutical Bulletin, 2002
    Co-Authors: Masaki Baba, Hoyoku Nishino, Yoshihito Okada, Ryoya Asano, Ikumi Takigami, Tetsuyuki Takahashi, Masayoshi Ohmura, Hajime Sugimoto, Tadashi Arika, Toru Okuyama
    Abstract:

    Isoliquiritigenin is a natural pigment with the simple chalcone structure, 4,2',4'-trihydroxychalcone. The effect of this compound on azoxymethane (AOM)-induced colonic aberrant crypt focus and tumor formation in ddY mice was examined. Administration of 15 ppm of Isoliquiritigenin in drinking water, significantly suppressed AOM-induced aberrant crypt focus formation (p<0.01), with an inhibitory ratio of 37.3%. Isoliquiritigenin also inhibited AOM-induced colon carcinogenesis by administration in a mixed diet. The average number of tumors was 14.6+/-8.9 items in the control group and were 7.3+/-7.3, 3.9+/-5.6, 4.7+/-6.5 items in the 10, 100 and 250 ppm in the Isoliquiritigenin treated groups, respectively. In histopathological studies, the tumors were identified as adenoma and adenocarcinoma, however, significant differences were not observed between the control group and Isoliquiritigenin treated groups. These results indicated that Isoliquiritigenin might be a potential chemopreventive agent against colon cancer.