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ABSTRACT: Xestospongin C (XC), which is a group of macrocyclic bis-1- oxaquinolizidines, is a potent inhibitor of sarcoendoplasmic reticulum calcium transport ATPase and IP3 receptor. Nevertheless, very less information is available regarding whether XC induces AML differentiation. We investigated the potential role of XC in the differentiation of human leukemia HL60 cells and mechanisms underlying XC actin. XC treatment inhibited proliferation by inducing G1-phase cell cycle arrest in the HL60 cells. In addition, XC induced differentiation of HL60 cells into the CD14+ monocytic lineage, which was indicated by morphological changes, nitroblue tetrazolium reduction assay, and expressions of CD11b and CD14 surface antigens. Our results also showed that XC promotes phagocytic activity and granularity in HL60 cells, suggesting that the cells are functionally activated. Furthermore, XC enhanced tumor necrosis factor (TNF)-α-mediated cytotoxic effect by increasing the numbers of TNF receptors. Moreover, we showed that XC activates extracellular signal-regulated kinase (ERK) pathway in the differentiation stages. Inhibition of ERK activation using PD98059 significantly decreased NBT+ HL60 cells induced by XC treatment. Taken together, the results show that XC promotes monocytic differentiation of HL60 cells via ERK pathway activation, suggesting that XC could be a candidate for use as a differentiation-inducing agent for AML treatment.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 02/2013; · 2.99 Impact Factor
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Long He,
Jae Hyuk Jang,
Hyun Gil Choi,
Sun Mi Lee,
Mei Hua Nan,
Sook Jung Jeong,
Zigang Dong,
Yong Tae Kwon,
Kyung Sang Lee,
Ki Won Lee,
Jong Kyeong Chung, Jong Seog Ahn,
Bo Yeon Kim
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ABSTRACT: Development of resistance to TNF-related apoptosis-inducing ligand (TRAIL) in tumor cells is one of the important problems in cancer treatment. Despite the previous report demonstrating that oligomycin suppressed TNF-induced apoptosis, in our screening of small molecules enhancing cancer cell death to TRAIL, oligomycin A (OMA) was found to enhance TRAIL-induced apoptosis in HeLa cells. CCAAT/enhancer-binding protein homologous protein (CHOP) was found to directly bind to death receptor 5 (DR5) promoter through endoplasmic reticulum stress (ER-stress) signaling and sensitize the cells to TRAIL. Among ER-stress associated proteins, OMA triggered the inositol-requiring enzyme 1 (IRE1) signaling pathway, leading to X-binding protein 1 (XBP1) splicing, CHOP expression and DR5 upregulation. In contrast, small-interfering RNA (siRNA) of CHOP reduced the number of apoptotic cells in response to the co-treatment of TRAIL and OMA. Collectively, our data suggest that OMA enhances apoptotic death of cervical cancer cells to TRAIL through upregulation of CHOP-mediated DR5 expression following ER-stress. © 2011 Wiley Periodicals, Inc.
Molecular Carcinogenesis 02/2013; 52(2):85-93. · 3.16 Impact Factor
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ABSTRACT: We investigated whether verrucarin A (VA) sensitizes HepG2 hepatoma cells to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis. We found that VA alone induces little apoptosis, but when combined with TRAIL (VA/TRAIL), it triggered significant apoptosis, causing little or no toxicity in normal mouse splenocytes. VA/TRAIL-induced cell death is involved in the loss of mitochondrial transmembrane potential and the consequent activation of caspases. Because nuclear factor (NF)-κB inhibition has been known as a critical target in TRAIL-mediated apoptosis, we also investigated the role of NF-κB in VA/TRAIL treatment. We found that VA upregulated the DNA binding activity of NF-κB, but that the antioxidants glutathione and Nacetyl- L-cysteine, as well as NF-κB inhibitor MG132, and mutant-IκB (m- IκB) transfection, significantly downregulated VA/TRAIL-induced cell death by inhibiting caspase-3 and NF-κB activities. Transfection of mutant-eIF2α also resulted in a decrease in VA/TRAIL-induced cell death by inhibiting of caspase-3, but not NF-κB activity. Although VA/TRAIL treatment led to an increase of DR5 expression, transfection of m-IκB had no influence on the DR5 expressional level. Finally, we showed that NF-κB-mediated Fas expression is critical to VA/TRAIL-induced apoptosis. Taken together, these results indicate that VA/TRAIL sensitizes HepG2 cells to apoptosis via NF-κB-mediated overexpression of Fas.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 01/2013; · 2.99 Impact Factor
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Sun-Ok Kim,
Krisada Sakchaisri,
Thimmegowda N R,
Nak Kyun Soung,
Jae-Hyuk Jang,
Young Sang Kim,
Kyung Sang Lee,
Yong Tae Kwon,
Yukihiro Asami, Jong Seog Ahn,
Raymond Leo Erikson,
Bo Yeon Kim
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ABSTRACT: STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G(2) phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent.
PLoS ONE 01/2013; 8(1):e53908. · 4.09 Impact Factor
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ABSTRACT: Protein tyrosine phosphatase 1B (PTP1B) plays a major role in the negative regulation of insulin signaling, and is thus considered as an attractive therapeutic target for the treatment of diabetes. Bioassay-guided investigation of the methylethylketone extract of marine-derived fungus Penicillium sp. JF-55 cultures afforded a new PTP1B inhibitory styrylpyrone-type metabolite named penstyrylpyrone (1), and two known metabolites, anhydrofulvic acid (2) and citromycetin (3). Compounds 1 and 2 inhibited PTP1B activity in a dose-dependent manner, and kinetic analyses of PTP1B inhibition suggested that these compounds inhibited PTP1B activity in a competitive manner. In an effort to gain more biological potential of the isolated compounds, the anti-inflammatory effects of compounds 1-3 were also evaluated. Among the tested compounds, only compound 1 inhibited the production of NO and PGE2, due to the inhibition of the expression of iNOS and COX-2. Penstyrylpyrone (1) also reduced TNF-α and IL-1β production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of IκB-α, NF-κB nuclear translocation, and NF-κB DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), an inhibitor of HO-1, it was verified that the inhibitory effects of penstyrylpyrone (1) on the pro-inflammatory mediators and NF-κB DNA binding activity were associated with the HO-1 expression. Therefore, these results suggest that penstyrylpyrone (1) suppresses PTP1B activity, as well as the production of pro-inflammatory mediators via NF-κB pathway, through expression of anti-inflammatory HO-1.
Marine Drugs 01/2013; 11(4):1409-26. · 3.85 Impact Factor
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Long He,
Junwon Lee,
Jae Hyuk Jang,
Krisada Sakchaisri,
Joon Sung Hwang,
Hyun Joo Cha-Molstad,
Kyung A Kim,
In Ja Ryoo,
Hee Gu Lee,
Sun Ok Kim,
Nak Kyun Soung,
Kyung Sang Lee,
Yong Tae Kwon,
Raymond Leo Erikson, Jong Seog Ahn,
Bo Yeon Kim
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ABSTRACT: Nuclear factor-κB (NF-κB) ligand (RANKL) was shown to induce osteoclast differentiation by increasing the expression of c-Fos, NFATc1 and TRAP. Salubrinal treatment to bone marrow macrophage (BMM) cells, however, significantly blocked NFATc1 expression and osteoclast differentiation by RANKL. Overexpression of NFATc1 further confirmed that NFATc1 is a key factor affected by salubrinal in osteoclast differentiation by RANKL. Unexpectedly, NFATc1 and c-Fos mRNA expressions were not affected by salubrinal, implicating that NFATc1 expression is regulated at a translational stage. In support of this, salubrinal increased the phosphorylation of a translation factor eIF2α, decreasing the global protein synthesis including NFATc1. In contrast, a phosphorylation mutant plasmid pLenti-eIF2α-S51A restored RANKL-induced NFATc1 expression and osteoclast differentiation even in the presence of salubrinal. Furthermore, knockdown of ATF4 significantly reduced salubrinal-induced osteoblast differentiation as evidenced by decreased calcium accumulation and lowered expressions of the osteoblast differentiation markers, alkaline phosphatase and RANKL in MC3T3-E1 osteoblast cells. Salubrinal treatment to co-cultured BMM and MC3T3-E1 cells also showed reduction of osteoclast differentiation. Finally, salubrinal efficiently blocked osteoporosis in mice model treated with RANKL as evidenced by elevated bone mineral density (BMD) and other osteoporosis factors. Collectively, our data indicate that salubrinal could affect the differentiation of both osteoblast and osteoclast, and be developed as an excellent anti-osteoporosis drug. In addition, modulation of ATF4 and NFATc1 expressions through eIF2α phosphorylation could be a valuable target for the treatment of osteoporosis.
Cellular signalling 11/2012; · 4.09 Impact Factor
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Pham Thi Thu Huong,
Nak Kyun Soung,
Jae Hyuk Jang,
Hyun Joo Cha-Molstad,
Krisada Sakchaisri,
Sun Ok Kim,
Jun Min Jang,
Kyoon Eon Kim,
Kyung Sang Lee,
Yong Tae Kwon,
Raymond Leo Erikson, Jong Seog Ahn,
Bo Yeon Kim
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ABSTRACT: Centrosomal proteins play important roles in cell cycle. Among them, the centrosomal protein of 131kDa (CEP131) has been reported as a critical factor for cilia formation which is related with development, signaling, and various diseases, the malfunction of cilia leading to cancer. Specificity protein 1 (SP1), known as a centrosome regulator, is an essential transcription factor regulating the genes involved in multiple cellular processes such as cell cycle, apoptosis, and DNA damages. In this study, we explored the crucial role of SP1 in regulation of CEP131 gene transcription. A deletion analysis of the CEP131 promoter region revealed dominant promoter elements within the sequence between -400bp and -200bp, which contained consensus binding sites for SP1. Electrophoretic mobility shift assay (EMSA) and chromatin immuno-precipitation (ChIP) assay further confirmed the direct binding of SP1 to the CEP131 promoter. On the other hand, CEP131 transcription could be inhibited by mithramycin (a GC-rich region inhibitor), but exogenous expression of SP1 could increase CEP131 expression as evidenced by a reporter gene assay. In addition, mutation of several SP1 binding sites revealed four SP1 binding sites at -244/-225, -258/-239, -304/-283 and -323/-304 that strongly affect CEP131 expression. Hence, it is suggested that SP1 is a pivotal transcription factor for the regulation of CEP131 expression, consequently leading the control of centrosome functions.
Gene 11/2012; · 2.34 Impact Factor
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ABSTRACT: Geldanamycin (GM) and its analogs are important anticancer agents that inhibit heat shock protein (Hsp) 90, which is a major chaperone protein in cancer cells. Accordingly, based on interest in obtaining novel natural GM derivatives, the potential of Streptomyces hygroscopicus JCM4427, a GM producer, was explored for novel natural GM derivative(s), resulting in the discovery of new GM analogs as a biosynthetic shunt product and intermediates from its fermentation broth. In this study, the fermentation, isolation, structure determination, and biological activity of the compounds, two new tetracyclic thiazinogeldanamycin (1) and 19-hydroxy-4,5-dihydrogeldanamycin (3), together with the three known 4,5-dihydrothiazinogeldanamycin (2), reblastatin (4), and 17-demethoxy-reblastatin (5), are described.
Journal of Microbiology and Biotechnology 11/2012; 22(11):1478-81. · 1.38 Impact Factor
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ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the most promising candidates for new cancer therapeutics. However, resistance to TRAIL in some cancers remains a current problem in recent. The protein-folding compartment of the endoplasmic reticulum (ER) is particularly sensitive to disturbances, which, if severe, may trigger apoptosis. Therefore, we examined whether verrucarin A (VA) sensitize TRAIL-induced apoptosis in cancer cells by induction of ER stress. We first found that VA induces a major molecule of ER stress, CCAAT/enhancer binding protein homologous protein (CHOP)-dependent DR5 induction and subsequently increases TRAIL-induced cleavage of caspases and PARP in TRAIL-resistant Hep3B cells. Importantly, the transient knockdown using siRNA for CHOP abrogated VA-induced DR5 expression and attenuated TRAIL-induced apoptosis. Treatment with VA also increased the levels of phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), which is a common cellular response of ER stress. Furthermore, salubrinal, a specific eIF2α phosphorylation-inducing agent, increased CHOP and DR5 expression in the presence of VA. In contrast, transfection of mutant-eIF2α significantly reversed VA-induced apoptosis with downregulation of CHOP-dependent DR5 expression. Therefore, VA-induced eIF2α phosphorylation seemed to be important for CHOP and DR5 upregulation and TRAIL-induced apoptosis. In addition, generation of reactive oxygen species (ROS) is an effector molecular in sensitization of VA-induced ER stress. We concluded that VA triggers TRAIL-induced apoptosis by eIF2α/CHOP-dependent DR5 induction via ROS generation.
Toxicology in Vitro 09/2012; · 2.78 Impact Factor
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ABSTRACT: Geldanamycin (GM) is a naturally occurring anticancer agent isolated from several strains of Streptomyces hygroscopicus. However, its potential clinical utility is compromised by its severe toxicity and poor water solubility. For this reason, considerable efforts are under way to make new derivatives that have both good clinical efficacy and high water solubility. On the other hand, glycosylation is often a step that improves the water solubility and/or biological activity in many natural products of biosynthesis. Here, we report the facile production of glucose-conjugated nonbenzoquinone GM analogs using the Bacillus UDP-glycosyltransferase BL-C. Five aglycon substrates containing nonbenzoquinone aromatic rings were chosen to validate the in vitro glycosylation reaction. Putative glucoside compounds were determined through the presence of a product peak(s) and were also verified using LC/MS analyses. Further, the chemical structures of new glucoside compounds 6 and 7 were elucidated using spectroscopy data. These glucoside compounds showed a dramatic improvement in water solubility compared with that of the original aglycon, nonbenzoquinone GM.
Applied and environmental microbiology 08/2012; 78(21):7680-6. · 3.69 Impact Factor
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Yukihiro Asami,
Jae-Hyuk Jang,
Hyuncheol Oh,
Jae Hak Sohn,
Jong Won Kim,
Dong Oh Moon,
Osong Kwon,
Makoto Kawatani,
Hiroyuki Osada,
Bo Yeon Kim, Jong Seog Ahn
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ABSTRACT: Violaceol-I and -II were isolated from a fractionated library of marine-derived fungal metabolites. These compounds increased the calcium ion concentration inside the cell and caused F-actin aggregation in rat fibroblast 3Y1 cells within 3 h resulting in cell shape elongation. Calcium chelator BAPTA-AM (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) inhibited violaceol-I and -II induced F-actin aggregation in 3Y1 cells, and hence violaceol-I and -II act in a calcium dependent manner. Violaceol-I and -II inhibited G-actin polymerization in vitro in a dose-dependent manner and strongly associated with G-actin, at dissociation equilibrium constants of 1.44 × 10(-8) M and 2.52 × 10(-9) M respectively. Here we report the identification of a novel function of violaceol-I and -II as actin inhibitors. Violaceol-I and -II induced cell shape elongation through F-actin aggregation in 3Y1 fibroblasts. These compounds may give researchers new insights into the role of actin in tumorigenesis and lead to the development of additional anti-tumor drugs.
Bioscience Biotechnology and Biochemistry 08/2012; 76(8):1431-7. · 1.28 Impact Factor
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The Journal of Antibiotics 08/2012; 65(8):437-40. · 1.65 Impact Factor
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ABSTRACT: In the continued search for melanogenesis inhibitors from microbial metabolites, we found that the culture broth of Clitocybe sp. MKACC 53267 inhibited melanogenesis in B16F10 melanoma cells. The active component was purified by solvent extraction, silica gel chromatography, Sephadex LH-20 column chromatography, and finally by preparative HPLC. Its structure was determined as 5- pentyl-2-furaldehyde on the basis of the UV, NMR, and MS spectroscopic analysis. The 5-pentyl-2-furaldehyde potently inhibited melanogenesis in B16F10 cells with an IC50 value of 8.4 microgram/ml, without cytotoxicity.
Journal of Microbiology and Biotechnology 06/2012; 22(6):814-7. · 1.38 Impact Factor
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Yukihiro Asami,
Jae-Hyuk Jang,
Nak-Kyun Soung,
Long He,
Dong Oh Moon,
Jong Won Kim,
Hyuncheol Oh,
Makoto Muroi,
Hiroyuki Osada,
Bo Yeon Kim, Jong Seog Ahn
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ABSTRACT: Previously we reported the identification of a new oxepin-containing diketopiperazine-type marine fungal metabolite, named protuboxepin A which showed antiproliferative activity in several cancer cell lines. In this study we elucidated the mechanism by which protuboxepin A induces cancer cell growth inhibition. Here we report that protuboxepin A induced round-up morphology, M phase arrest, and an increase in the subG(1) population in tumor cells in a dose dependent manner. Our investigations revealed that protuboxepin A directly binds to α,β-tubulin and stabilizes tubulin polymerization thus disrupting microtubule dynamics. This disruption leads to chromosome misalignment and metaphase arrest which induces apoptosis in cancer. Overall, we identified protuboxepin A as a microtubule-stabilizing agent which has a distinctly different chemical structure from previously reported microtubule inhibitors. These results indicate that protuboxepin A has a potential of being a new and effective anti-cancer drug.
Bioorganic & medicinal chemistry 04/2012; 20(12):3799-806. · 2.82 Impact Factor
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Kangdong Liu,
Chanmi Park,
Shengqing Li,
Ki Won Lee,
Haidan Liu,
Long He,
Nak Kyun Soung, Jong Seog Ahn,
Ann M Bode,
Ziming Dong,
Bo Yeon Kim,
Zigang Dong
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ABSTRACT: Phosphatidylinositol 3-kinase (PI3-K) amplification and phosphatase and tensin homolog (PTEN) deletion-caused Akt activation contribute to the development of prostate cancer. Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5 and functions in the phosphorylation of Akt at Ser473. Herein, we report that mTORC2 plays an important role in PC3 androgen refractory prostate cell proliferation and anchorage-independent growth. Aloe-emodin, a natural compound found in aloe, inhibited both proliferation and anchorage-independent growth of PC3 cells. Protein content analysis suggested that activation of the downstream substrates of mTORC2, Akt and PKCα, was inhibited by aloe-emodin treatment. Pull-down assay and in vitro kinase assay results indicated that aloe-emodin could bind with mTORC2 in cells and inhibit its kinase activity. Aloe-emodin also exhibited tumor suppression effects in vivo in an athymic nude mouse model. Collectively, our data suggest that mTORC2 plays an important role in prostate cancer development and aloe-emodin suppresses prostate cancer progression by targeting mTORC2.
Carcinogenesis 04/2012; 33(7):1406-11. · 5.70 Impact Factor
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Jae-Hyuk Jang,
Yukihiro Asami,
Jun-Pil Jang,
Sun-Ok Kim,
Dong Oh Moon,
Kee-Sun Shin,
Daisuke Hashizume,
Makoto Muroi,
Tamio Saito,
Hyuncheol Oh,
Bo Yeon Kim,
Hiroyuki Osada, Jong Seog Ahn
Journal of the American Chemical Society 04/2012; · 9.91 Impact Factor
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Dong-Oh Moon,
Bo Yeon Kim,
Jae Hyuk Jang,
Mun-Ock Kim,
R G P T Jayasooriya,
Chang-Hee Kang,
Yung Hyun Choi,
Sung-Kwon Moon,
Wun-Jae Kim, Jong Seog Ahn,
Gi-Young Kim
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ABSTRACT: The anti-apoptotic oncogene K-RAS is hypothesized to increase the antioxidant status of cells, thereby protecting them from generation of reactive oxygen species (ROS). Therefore, we examined whether K-RAS overcomes hydrogen peroxide (H2O2)-mediated apoptosis in the human fetal prostate epithelial cell 267B1. In this study, we found that treatment of 267B1 cells with H2O2 resulted in significant reduction of cell growth, which was associated with cytochrome-c release and caspase-3 activation. However, mutated K-RAS transformation (268B1/K-RAS) rendered 267B1 cells reduction of the resistance to H2O2-induced apoptosis through suppression of ROS generation. In addition, we analyzed profiling of gene expression in K-RAS transformation and found that gamma-glutamyltransferase 2 (GGT2) most highly expressed. Transient knockdown of K-RAS resulted in a significant downregulation of GGT gene expression. We also revealed that expression of GGT2 gene is closely regulated by the ERK signal pathway in 267B1/K-RAS cells. In addition, the anti-apoptotic effect of mutated K-RAS was attenuated by treatment with GGT2 RNA interference through inhibition of ROS generation, suggesting that mutated K-RAS mediates resistance to H2O2-induced apoptosis through GGT2 activation. These results importantly provide mechanistic insights on the anti-apoptotic activity of mutated K-RAS.
Toxicology in Vitro 04/2012; 26(3):429-34. · 2.78 Impact Factor
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Osong Kwon,
Nak Kyun Soung,
N R Thimmegowda,
Sook Jung Jeong,
Jae Hyuk Jang,
Dong-Oh Moon,
Jong Kyeong Chung,
Kyung Sang Lee,
Yong Tae Kwon,
Raymond Leo Erikson, Jong Seog Ahn,
Bo Yeon Kim
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ABSTRACT: Patulin is a fungal mycotoxin of Aspergilus and Penicillium that is commonly found in rotting fruits and exerts its potential toxic effect mainly by reactive oxygen species (ROS) generation. However, the effect of patulin on cancer cells as well as its intracellular mechanism has been controversial and not clearly defined yet. In this study, patulin was found to induce G1/S accumulation and cell growth arrest accompanied by caspase-3 activation, PARP cleavage and ATF3 expression in human colon cancer cell line HCT116. Ser/Thr phosphorylation of a transcription factor, EGR-1, was increased while its expression did not change upon patulin treatment to the cells. Knockdown of ATF3 and EGR-1 using their respective siRNAs showed EGR-1 dependent ATF3 expression. Moreover, treatment of the cells with antioxidants N-acetylcysteine (NAC) and glutathione (GSH) revealed that patulin induced ATF3 expression and apoptosis were dependent on ROS generation. ATF3 expression was also increased by patulin in other colorectal cancer cell types, Caco2 and SW620. Collectively, our data present a new anti-cancer molecular mechanism of patulin, suggesting EGR-1 and ATF3 as critical targets for the development of anti-cancer chemotherapeutics. In this regard, patulin could be a candidate for the treatment of colorectal cancers.
Cellular signalling 04/2012; 24(4):943-50. · 4.09 Impact Factor
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Long He,
Junwon Lee,
Jae Hyuk Jang,
Sung-Hoon Lee,
Mei Hua Nan,
Byung-Chul Oh,
Sang Gu Lee,
Hong Hee Kim,
Nak Kyun Soung, Jong Seog Ahn,
Bo Yeon Kim
[show abstract]
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ABSTRACT: Ginsenoside Rh2 is one of the most active components of red ginseng, controlling cancer and other metabolic diseases including osteoclast differentiation. However, the molecular mechanism underlying the inhibition of osteoclast differentiation by ginsenoside Rh2 remains poorly understood. In the present study, it was found that ginsenoside Rh2 suppressed osteoclast differentiation from bone marrow macrophages (BMMs) treated with receptor activator of nuclear factor κB ligand (RANKL) without any cytotoxicity. Ginsenoside Rh2 significantly reduced RANKL-induced expression of transcription factors, c-Fos and nuclear factor of activated T-cells (NFATc1), as well as osteoclast markers, TRAP and OSCAR. In defining the signaling pathways, ginsenoside Rh2 was shown to moderately inhibit NF-κB activation and ERK phosphorylation in response to RANKL stimulation in BMM cells without any effect on p38 and c-Jun N-terminal kinase (JNK). Finally, ginsenoside Rh2 blocked osteoporosis in vivo as confirmed by restored bone mineral density (BMD) and other markers associated osteoclast differentiation. Hence, it is suggested that ginsenoside Rh2 could suppress RANKL-induced osteoclast differentiation in vitro and in vivo through the regulation of c-Fos and NFATc1 expressions, not excluding the involvement of NF-κB and ERK. Ginsenoside Rh2 is also suggested to be developed as a therapeutic drug for prevention and treatment of osteoporosis.
Bone 03/2012; 50(6):1207-13. · 4.02 Impact Factor
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Jun-Pil Jang,
Jae-Hyuk Jang,
Nak-Kyun Soung,
Hye-Min Kim,
Sook-Jung Jeong,
Yukihiro Asami,
Kee-Sun Shin,
Mee Ree Kim,
Hyuncheol Oh,
Bo Yeon Kim, Jong Seog Ahn
The Journal of Antibiotics 02/2012; 65(4):215-7. · 1.65 Impact Factor
