Ganoderma lucidum polysaccharides prevent platelet-derived growth factor-stimulated smooth muscle cell proliferation in vitro and neointimal hyperplasia in the endothelial-denuded artery in vivo

Shu-Huei Wang, Chan-Jung Liang, Yu-Wen Weng, Yung-Hsiang Chen, Hsien-Yeh Hsu, Hsiung-Fei Chien, Jaw-Shiun Tsai, Ying-Chin Tseng, Chi-Yuan Li, Yuh-Lien Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Ganoderma lucidum is used in traditional Chinese medicine to prevent or treat a variety of diseases, including cardiovascular disorders. We previously demonstrated that a glucan-containing extract of Reishi polysaccharides (EORP) has the potent anti-inflammatory action of reducing ICAM-1 expression in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and LPS-treated mice. In the present study, we examined whether EORP inhibited platelet-derived growth factor-BB (PDGF)-stimulated HASMC proliferation and the mechanism involved. EORP dose-dependently reduced cell numbers and DNA synthesis of PDGF-treated HASMCs in vitro. EORP also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21Cip1 and upregulation of the cyclin-dependent kinase inhibitor p27Kip1. The anti-proliferative effect of EORP was partly mediated by downregulation of PDGF-induced JNK phosphorylation. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice were fed a diet containing 100mg/kg/day of EORP. On day 14, both cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima and the neointima/media area ratio (0.67±0.03 vs. 1.46±0.30) were significantly reduced. Our data show that EORP interferes with the mitogenic activation of JNK, preventing entry of HASMCs into the cell cycle in vitro and reducing cell proliferation in the neointima and decreasing the neointimal area in vivo. Thus, EORP may represent a safe and effective novel approach to the prevention and treatment of vascular proliferative diseases. © 2011 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)3063-3071
Number of pages9
JournalJournal of Cellular Physiology
Volume227
Issue number8
DOIs
Publication statusPublished - 2012
Externally publishedYes

Fingerprint

Reishi
Platelet-Derived Growth Factor
Cell proliferation
Smooth Muscle Myocytes
Hyperplasia
Polysaccharides
Muscle
Arteries
Cell Proliferation
Cells
Neointima
Lipopolysaccharides
Cell Cycle
Cyclin E
Phosphorylation
Glucans
Cyclin-Dependent Kinases
In Vitro Techniques
Cyclin D1
Cell Cycle Resting Phase

Keywords

  • cyclin D1
  • cyclin dependent kinase 4
  • cyclin dependent kinase inhibitor 1B
  • cyclin E
  • Janus kinase
  • plant extract
  • platelet derived growth factor
  • protein p21
  • reishi polysaccharide
  • unclassified drug
  • animal cell
  • animal experiment
  • animal model
  • animal tissue
  • article
  • cell count
  • cell cycle G0 phase
  • cell cycle G1 phase
  • cell cycle progression
  • cell proliferation
  • cell viability
  • controlled study
  • diet
  • DNA synthesis
  • endothelium
  • enzyme activation
  • enzyme phosphorylation
  • erythrocyte
  • femoral artery
  • Ganoderma lucidum
  • human
  • human cell
  • hyperplasia
  • in vitro study
  • in vivo study
  • male
  • mitogenesis
  • mouse
  • neointimal hyperplasia
  • nonhuman
  • priority journal
  • protein expression
  • smooth muscle fiber
  • upregulation
  • Animals
  • Aorta
  • Cell Cycle
  • Cell Death
  • Cell Proliferation
  • Drugs, Chinese Herbal
  • Gene Knockdown Techniques
  • Humans
  • Lipopolysaccharides
  • Male
  • MAP Kinase Kinase 4
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Smooth Muscle
  • Neointima
  • Phosphorylation
  • Platelet-Derived Growth Factor
  • Polysaccharides
  • Reishi
  • Mus

Cite this

Ganoderma lucidum polysaccharides prevent platelet-derived growth factor-stimulated smooth muscle cell proliferation in vitro and neointimal hyperplasia in the endothelial-denuded artery in vivo. / Wang, Shu-Huei; Liang, Chan-Jung; Weng, Yu-Wen; Chen, Yung-Hsiang; Hsu, Hsien-Yeh; Chien, Hsiung-Fei; Tsai, Jaw-Shiun; Tseng, Ying-Chin; Li, Chi-Yuan; Chen, Yuh-Lien.

In: Journal of Cellular Physiology, Vol. 227, No. 8, 2012, p. 3063-3071.

Research output: Contribution to journalArticle

Wang, Shu-Huei ; Liang, Chan-Jung ; Weng, Yu-Wen ; Chen, Yung-Hsiang ; Hsu, Hsien-Yeh ; Chien, Hsiung-Fei ; Tsai, Jaw-Shiun ; Tseng, Ying-Chin ; Li, Chi-Yuan ; Chen, Yuh-Lien. / Ganoderma lucidum polysaccharides prevent platelet-derived growth factor-stimulated smooth muscle cell proliferation in vitro and neointimal hyperplasia in the endothelial-denuded artery in vivo. In: Journal of Cellular Physiology. 2012 ; Vol. 227, No. 8. pp. 3063-3071.
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title = "Ganoderma lucidum polysaccharides prevent platelet-derived growth factor-stimulated smooth muscle cell proliferation in vitro and neointimal hyperplasia in the endothelial-denuded artery in vivo",
abstract = "Ganoderma lucidum is used in traditional Chinese medicine to prevent or treat a variety of diseases, including cardiovascular disorders. We previously demonstrated that a glucan-containing extract of Reishi polysaccharides (EORP) has the potent anti-inflammatory action of reducing ICAM-1 expression in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and LPS-treated mice. In the present study, we examined whether EORP inhibited platelet-derived growth factor-BB (PDGF)-stimulated HASMC proliferation and the mechanism involved. EORP dose-dependently reduced cell numbers and DNA synthesis of PDGF-treated HASMCs in vitro. EORP also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21Cip1 and upregulation of the cyclin-dependent kinase inhibitor p27Kip1. The anti-proliferative effect of EORP was partly mediated by downregulation of PDGF-induced JNK phosphorylation. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice were fed a diet containing 100mg/kg/day of EORP. On day 14, both cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima and the neointima/media area ratio (0.67±0.03 vs. 1.46±0.30) were significantly reduced. Our data show that EORP interferes with the mitogenic activation of JNK, preventing entry of HASMCs into the cell cycle in vitro and reducing cell proliferation in the neointima and decreasing the neointimal area in vivo. Thus, EORP may represent a safe and effective novel approach to the prevention and treatment of vascular proliferative diseases. {\circledC} 2011 Wiley Periodicals, Inc.",
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author = "Shu-Huei Wang and Chan-Jung Liang and Yu-Wen Weng and Yung-Hsiang Chen and Hsien-Yeh Hsu and Hsiung-Fei Chien and Jaw-Shiun Tsai and Ying-Chin Tseng and Chi-Yuan Li and Yuh-Lien Chen",
note = "被引用次數:6 Export Date: 16 March 2016 CODEN: JCLLA 通訊地址: Chen, Y.-L.; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Ren-Ai Rd, Taipei 100, Taiwan; 電子郵件: ylchenv@ntu.edu.tw 化學物質/CAS: Janus kinase, 161384-16-3; cyclin dependent kinase 4, 147014-97-9; protein p21, 85306-28-1; Drugs, Chinese Herbal; Lipopolysaccharides; MAP Kinase Kinase 4, 2.7.12.2; Platelet-Derived Growth Factor; Polysaccharides 參考文獻: Andres, V., Castro, C., Antiproliferative strategies for the treatment of vascular proliferative disease (2003) Curr Vasc Pharmacol, 1, pp. 85-98; Desbois-Mouthon, C., Cadoret, A., Blivet-Van Eggelpoel, M.J., Bertrand, F., Caron, M., Atfi, A., Cherqui, G., Capeau, J., Insulin-mediated cell proliferation and survival involve inhibition of c-Jun N-terminal kinases through a phosphatidylinositol 3-kinase- and mitogen-activated protein kinase phosphatase-1-dependent pathway (2000) Endocrinology, 141, pp. 922-931; Dudhgaonkar, S., Thyagarajan, A., Sliva, D., Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum (2009) Int Immunopharmacol, 9, pp. 1272-1280; Dzau, V.J., Braun-Dullaeus, R.C., Sedding, D.G., Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies (2002) Nat Med, 8, pp. 1249-1256; Evans, S., Dizeyi, N., Abrahamsson, P.A., Persson, J., The effect of a novel botanical agent TBS-101 on invasive prostate cancer in animal models (2009) Anticancer Res, 29, pp. 3917-3924; Gao, Y., Gao, H., Chan, E., Tang, W., Xu, A., Yang, H., Huang, M., Zhou, S., Antitumor activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, in mice (2005) Immunol Invest, 34, pp. 171-198; Ghosh, S.S., Gehr, T.W., Ghosh, S., Fakhry, I., Sica, D.A., Lyall, V., Schoolwerth, A.C., PPARgamma ligand attenuates PDGF-induced mesangial cell proliferation: Role of MAP kinase (2003) Kidney Int, 64, pp. 52-62; Golias, C.H., Charalabopoulos, A., Charalabopoulos, K., Cell proliferation and cell cycle control: A mini review (2004) Int J Clin Pract, 58, pp. 1134-1141; Heldin, C.H., Westermark, B., Mechanism of action and in vivo role of platelet-derived growth factor (1999) Physiol Rev, 79, pp. 1283-1316; Hsu, H.Y., Hua, K.F., Lin, C.C., Lin, C.H., Hsu, J., Wong, C.H., Extract of Reishi polysaccharides induces cytokine expression via TLR4-modulated protein kinase signaling pathways (2004) J Immunol, 173, pp. 5989-5999; Ishizawa, K., Izawa-Ishizawa, Y., Ohnishi, S., Motobayashi, Y., Kawazoe, K., Hamano, S., Tsuchiya, K., Tamaki, T., Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells (2009) J Pharmacol Sci, 109, pp. 257-264; Jiang, J., Slivova, V., Harvey, K., Valachovicova, T., Sliva, D., Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling (2004) Nutr Cancer, 49, pp. 209-216; Jiang, J., Slivova, V., Sliva, D., Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling (2006) Int J Oncol, 29, pp. 695-703; Kim, H.S., Cho, H.J., Park, S.J., Park, K.W., Chae, I.H., Oh, B.H., Park, Y.B., Lee, M.M., The essential role of p21 in radiation-induced cell cycle arrest of vascular smooth muscle cell (2004) J Mol Cell Cardiol, 37, pp. 871-880; Lin, S.J., Shyue, S.K., Hung, Y.Y., Chen, Y.H., Ku, H.H., Chen, J.W., Tam, K.B., Chen, Y.L., Superoxide dismutase inhibits the expression of vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 induced by tumor necrosis factor-alpha in human endothelial cells through the JNK/p38 pathways (2005) Arterioscler Thromb Vasc Biol, 25, pp. 334-340; Lin, C.Y., Chen, Y.H., Hsu, H.Y., Wang, S.H., Liang, C.J., Kuan, I.I., Wu, P.J., Chen, Y.L., Ganoderma lucidum polysaccharides attenuate endotoxin-induced intercellular cell adhesion molecule-1 expression in cultured smooth muscle cells and in the neointima in mice (2010) J Agric Food Chem, 58, pp. 9563-9571; Miyazaki, T., Nishijima, M., Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum (1981) Chem Pharm Bull, 29, pp. 3611-3616; Moon, S.K., Kim, H.M., Lee, Y.C., Kim, C.H., Disialoganglioside (GD3) synthase gene expression suppresses vascular smooth muscle cell responses via the inhibition of ERK1/2 phosphorylation, cell cycle progression, and matrix metalloproteinase-9 expression (2004) J Biol Chem, 279, pp. 33063-33070; Ross, R., Cell biology of atherosclerosis (1995) Annu Rev Physiol, 57, pp. 791-804; Sata, M., Maejima, Y., Adachi, F., Fukino, K., Saiura, A., Sugiura, S., Aoyagi, T., Nagai, R., A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia (2000) J Mol Cell Cardiol, 32, pp. 2097-2104; Shankland, S.J., Wolf, G., Cell cycle regulatory proteins in renal disease: Role in hypertrophy, proliferation, and apoptosis (2000) Am J Physiol Renal Physiol, 278, pp. F515-F529; Shiao, M.S., Natural products of the medicinal fungus Ganoderma lucidum: Occurrence, biological activities, and pharmacological functions (2003) Chem Rec, 3, pp. 172-180; Sliva, D., Labarrere, C., Slivova, V., Sedlak, M., Lloyd Jr., F.P., Ho, N.W., Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells (2002) Biochem Biophys Res Commun, 298, pp. 603-612; Sun, J., He, H., Xie, B.J., Novel antioxidant peptides from fermented mushroom Ganoderma lucidum (2004) J Agric Food Chem, 52, pp. 6646-6652; Thyagarajan, A., Jiang, J., Hopf, A., Adamec, J., Sliva, D., Inhibition of oxidative stress-induced invasiveness of cancer cells by Ganoderma lucidum is mediated through the suppression of interleukin-8 secretion (2006) Int J Mol Med, 18, pp. 657-664; Uchida, K., Sasahara, M., Morigami, N., Hazama, F., Kinoshita, M., Expression of platelet-derived growth factor B-chain in neointimal smooth muscle cells of balloon injured rabbit femoral arteries (1996) Atherosclerosis, 124, pp. 9-23; Wang, S.Y., Hsu, M.L., Hsu, H.C., Tzeng, C.H., Lee, S.S., Shiao, M.S., Ho, C.K., The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes (1997) Int J Cancer, 70, pp. 699-705; Wang, Y.Y., Khoo, K.H., Chen, S.T., Lin, C.C., Wong, C.H., Lin, C.H., Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: Functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities (2002) Bioorg Med Chem, 10, pp. 1057-1062; Wang, G.J., Huang, Y.J., Chen, D.H., Lin, Y.L., Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor (2009) Phytother Res, 23, pp. 833-839; Xie, J.T., Wang, C.Z., Wicks, S., Yin, J.J., Kong, J., Li, J., Li, Y.C., Yuan, C.S., Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells (2006) Exp Oncol, 28, pp. 25-29; Zhan, Y., Kim, S., Izumi, Y., Izumiya, Y., Nakao, T., Miyazaki, H., Iwao, H., Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression (2003) Arterioscler Thromb Vasc Biol, 23, pp. 795-801",
year = "2012",
doi = "10.1002/jcp.23053",
language = "English",
volume = "227",
pages = "3063--3071",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - Ganoderma lucidum polysaccharides prevent platelet-derived growth factor-stimulated smooth muscle cell proliferation in vitro and neointimal hyperplasia in the endothelial-denuded artery in vivo

AU - Wang, Shu-Huei

AU - Liang, Chan-Jung

AU - Weng, Yu-Wen

AU - Chen, Yung-Hsiang

AU - Hsu, Hsien-Yeh

AU - Chien, Hsiung-Fei

AU - Tsai, Jaw-Shiun

AU - Tseng, Ying-Chin

AU - Li, Chi-Yuan

AU - Chen, Yuh-Lien

N1 - 被引用次數:6 Export Date: 16 March 2016 CODEN: JCLLA 通訊地址: Chen, Y.-L.; Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Ren-Ai Rd, Taipei 100, Taiwan; 電子郵件: ylchenv@ntu.edu.tw 化學物質/CAS: Janus kinase, 161384-16-3; cyclin dependent kinase 4, 147014-97-9; protein p21, 85306-28-1; Drugs, Chinese Herbal; Lipopolysaccharides; MAP Kinase Kinase 4, 2.7.12.2; Platelet-Derived Growth Factor; Polysaccharides 參考文獻: Andres, V., Castro, C., Antiproliferative strategies for the treatment of vascular proliferative disease (2003) Curr Vasc Pharmacol, 1, pp. 85-98; Desbois-Mouthon, C., Cadoret, A., Blivet-Van Eggelpoel, M.J., Bertrand, F., Caron, M., Atfi, A., Cherqui, G., Capeau, J., Insulin-mediated cell proliferation and survival involve inhibition of c-Jun N-terminal kinases through a phosphatidylinositol 3-kinase- and mitogen-activated protein kinase phosphatase-1-dependent pathway (2000) Endocrinology, 141, pp. 922-931; Dudhgaonkar, S., Thyagarajan, A., Sliva, D., Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum (2009) Int Immunopharmacol, 9, pp. 1272-1280; Dzau, V.J., Braun-Dullaeus, R.C., Sedding, D.G., Vascular proliferation and atherosclerosis: New perspectives and therapeutic strategies (2002) Nat Med, 8, pp. 1249-1256; Evans, S., Dizeyi, N., Abrahamsson, P.A., Persson, J., The effect of a novel botanical agent TBS-101 on invasive prostate cancer in animal models (2009) Anticancer Res, 29, pp. 3917-3924; Gao, Y., Gao, H., Chan, E., Tang, W., Xu, A., Yang, H., Huang, M., Zhou, S., Antitumor activity and underlying mechanisms of ganopoly, the refined polysaccharides extracted from Ganoderma lucidum, in mice (2005) Immunol Invest, 34, pp. 171-198; Ghosh, S.S., Gehr, T.W., Ghosh, S., Fakhry, I., Sica, D.A., Lyall, V., Schoolwerth, A.C., PPARgamma ligand attenuates PDGF-induced mesangial cell proliferation: Role of MAP kinase (2003) Kidney Int, 64, pp. 52-62; Golias, C.H., Charalabopoulos, A., Charalabopoulos, K., Cell proliferation and cell cycle control: A mini review (2004) Int J Clin Pract, 58, pp. 1134-1141; Heldin, C.H., Westermark, B., Mechanism of action and in vivo role of platelet-derived growth factor (1999) Physiol Rev, 79, pp. 1283-1316; Hsu, H.Y., Hua, K.F., Lin, C.C., Lin, C.H., Hsu, J., Wong, C.H., Extract of Reishi polysaccharides induces cytokine expression via TLR4-modulated protein kinase signaling pathways (2004) J Immunol, 173, pp. 5989-5999; Ishizawa, K., Izawa-Ishizawa, Y., Ohnishi, S., Motobayashi, Y., Kawazoe, K., Hamano, S., Tsuchiya, K., Tamaki, T., Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells (2009) J Pharmacol Sci, 109, pp. 257-264; Jiang, J., Slivova, V., Harvey, K., Valachovicova, T., Sliva, D., Ganoderma lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB signaling (2004) Nutr Cancer, 49, pp. 209-216; Jiang, J., Slivova, V., Sliva, D., Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling (2006) Int J Oncol, 29, pp. 695-703; Kim, H.S., Cho, H.J., Park, S.J., Park, K.W., Chae, I.H., Oh, B.H., Park, Y.B., Lee, M.M., The essential role of p21 in radiation-induced cell cycle arrest of vascular smooth muscle cell (2004) J Mol Cell Cardiol, 37, pp. 871-880; Lin, S.J., Shyue, S.K., Hung, Y.Y., Chen, Y.H., Ku, H.H., Chen, J.W., Tam, K.B., Chen, Y.L., Superoxide dismutase inhibits the expression of vascular cell adhesion molecule-1 and intracellular cell adhesion molecule-1 induced by tumor necrosis factor-alpha in human endothelial cells through the JNK/p38 pathways (2005) Arterioscler Thromb Vasc Biol, 25, pp. 334-340; Lin, C.Y., Chen, Y.H., Hsu, H.Y., Wang, S.H., Liang, C.J., Kuan, I.I., Wu, P.J., Chen, Y.L., Ganoderma lucidum polysaccharides attenuate endotoxin-induced intercellular cell adhesion molecule-1 expression in cultured smooth muscle cells and in the neointima in mice (2010) J Agric Food Chem, 58, pp. 9563-9571; Miyazaki, T., Nishijima, M., Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum (1981) Chem Pharm Bull, 29, pp. 3611-3616; Moon, S.K., Kim, H.M., Lee, Y.C., Kim, C.H., Disialoganglioside (GD3) synthase gene expression suppresses vascular smooth muscle cell responses via the inhibition of ERK1/2 phosphorylation, cell cycle progression, and matrix metalloproteinase-9 expression (2004) J Biol Chem, 279, pp. 33063-33070; Ross, R., Cell biology of atherosclerosis (1995) Annu Rev Physiol, 57, pp. 791-804; Sata, M., Maejima, Y., Adachi, F., Fukino, K., Saiura, A., Sugiura, S., Aoyagi, T., Nagai, R., A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia (2000) J Mol Cell Cardiol, 32, pp. 2097-2104; Shankland, S.J., Wolf, G., Cell cycle regulatory proteins in renal disease: Role in hypertrophy, proliferation, and apoptosis (2000) Am J Physiol Renal Physiol, 278, pp. F515-F529; Shiao, M.S., Natural products of the medicinal fungus Ganoderma lucidum: Occurrence, biological activities, and pharmacological functions (2003) Chem Rec, 3, pp. 172-180; Sliva, D., Labarrere, C., Slivova, V., Sedlak, M., Lloyd Jr., F.P., Ho, N.W., Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells (2002) Biochem Biophys Res Commun, 298, pp. 603-612; Sun, J., He, H., Xie, B.J., Novel antioxidant peptides from fermented mushroom Ganoderma lucidum (2004) J Agric Food Chem, 52, pp. 6646-6652; Thyagarajan, A., Jiang, J., Hopf, A., Adamec, J., Sliva, D., Inhibition of oxidative stress-induced invasiveness of cancer cells by Ganoderma lucidum is mediated through the suppression of interleukin-8 secretion (2006) Int J Mol Med, 18, pp. 657-664; Uchida, K., Sasahara, M., Morigami, N., Hazama, F., Kinoshita, M., Expression of platelet-derived growth factor B-chain in neointimal smooth muscle cells of balloon injured rabbit femoral arteries (1996) Atherosclerosis, 124, pp. 9-23; Wang, S.Y., Hsu, M.L., Hsu, H.C., Tzeng, C.H., Lee, S.S., Shiao, M.S., Ho, C.K., The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes (1997) Int J Cancer, 70, pp. 699-705; Wang, Y.Y., Khoo, K.H., Chen, S.T., Lin, C.C., Wong, C.H., Lin, C.H., Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: Functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities (2002) Bioorg Med Chem, 10, pp. 1057-1062; Wang, G.J., Huang, Y.J., Chen, D.H., Lin, Y.L., Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor (2009) Phytother Res, 23, pp. 833-839; Xie, J.T., Wang, C.Z., Wicks, S., Yin, J.J., Kong, J., Li, J., Li, Y.C., Yuan, C.S., Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells (2006) Exp Oncol, 28, pp. 25-29; Zhan, Y., Kim, S., Izumi, Y., Izumiya, Y., Nakao, T., Miyazaki, H., Iwao, H., Role of JNK, p38, and ERK in platelet-derived growth factor-induced vascular proliferation, migration, and gene expression (2003) Arterioscler Thromb Vasc Biol, 23, pp. 795-801

PY - 2012

Y1 - 2012

N2 - Ganoderma lucidum is used in traditional Chinese medicine to prevent or treat a variety of diseases, including cardiovascular disorders. We previously demonstrated that a glucan-containing extract of Reishi polysaccharides (EORP) has the potent anti-inflammatory action of reducing ICAM-1 expression in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and LPS-treated mice. In the present study, we examined whether EORP inhibited platelet-derived growth factor-BB (PDGF)-stimulated HASMC proliferation and the mechanism involved. EORP dose-dependently reduced cell numbers and DNA synthesis of PDGF-treated HASMCs in vitro. EORP also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21Cip1 and upregulation of the cyclin-dependent kinase inhibitor p27Kip1. The anti-proliferative effect of EORP was partly mediated by downregulation of PDGF-induced JNK phosphorylation. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice were fed a diet containing 100mg/kg/day of EORP. On day 14, both cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima and the neointima/media area ratio (0.67±0.03 vs. 1.46±0.30) were significantly reduced. Our data show that EORP interferes with the mitogenic activation of JNK, preventing entry of HASMCs into the cell cycle in vitro and reducing cell proliferation in the neointima and decreasing the neointimal area in vivo. Thus, EORP may represent a safe and effective novel approach to the prevention and treatment of vascular proliferative diseases. © 2011 Wiley Periodicals, Inc.

AB - Ganoderma lucidum is used in traditional Chinese medicine to prevent or treat a variety of diseases, including cardiovascular disorders. We previously demonstrated that a glucan-containing extract of Reishi polysaccharides (EORP) has the potent anti-inflammatory action of reducing ICAM-1 expression in lipopolysaccharide (LPS)-treated human aortic smooth muscle cells (HASMCs) and LPS-treated mice. In the present study, we examined whether EORP inhibited platelet-derived growth factor-BB (PDGF)-stimulated HASMC proliferation and the mechanism involved. EORP dose-dependently reduced cell numbers and DNA synthesis of PDGF-treated HASMCs in vitro. EORP also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21Cip1 and upregulation of the cyclin-dependent kinase inhibitor p27Kip1. The anti-proliferative effect of EORP was partly mediated by downregulation of PDGF-induced JNK phosphorylation. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice were fed a diet containing 100mg/kg/day of EORP. On day 14, both cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima and the neointima/media area ratio (0.67±0.03 vs. 1.46±0.30) were significantly reduced. Our data show that EORP interferes with the mitogenic activation of JNK, preventing entry of HASMCs into the cell cycle in vitro and reducing cell proliferation in the neointima and decreasing the neointimal area in vivo. Thus, EORP may represent a safe and effective novel approach to the prevention and treatment of vascular proliferative diseases. © 2011 Wiley Periodicals, Inc.

KW - cyclin D1

KW - cyclin dependent kinase 4

KW - cyclin dependent kinase inhibitor 1B

KW - cyclin E

KW - Janus kinase

KW - plant extract

KW - platelet derived growth factor

KW - protein p21

KW - reishi polysaccharide

KW - unclassified drug

KW - animal cell

KW - animal experiment

KW - animal model

KW - animal tissue

KW - article

KW - cell count

KW - cell cycle G0 phase

KW - cell cycle G1 phase

KW - cell cycle progression

KW - cell proliferation

KW - cell viability

KW - controlled study

KW - diet

KW - DNA synthesis

KW - endothelium

KW - enzyme activation

KW - enzyme phosphorylation

KW - erythrocyte

KW - femoral artery

KW - Ganoderma lucidum

KW - human

KW - human cell

KW - hyperplasia

KW - in vitro study

KW - in vivo study

KW - male

KW - mitogenesis

KW - mouse

KW - neointimal hyperplasia

KW - nonhuman

KW - priority journal

KW - protein expression

KW - smooth muscle fiber

KW - upregulation

KW - Animals

KW - Aorta

KW - Cell Cycle

KW - Cell Death

KW - Cell Proliferation

KW - Drugs, Chinese Herbal

KW - Gene Knockdown Techniques

KW - Humans

KW - Lipopolysaccharides

KW - Male

KW - MAP Kinase Kinase 4

KW - Mice

KW - Mice, Inbred C57BL

KW - Myocytes, Smooth Muscle

KW - Neointima

KW - Phosphorylation

KW - Platelet-Derived Growth Factor

KW - Polysaccharides

KW - Reishi

KW - Mus

U2 - 10.1002/jcp.23053

DO - 10.1002/jcp.23053

M3 - Article

VL - 227

SP - 3063

EP - 3071

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 8

ER -