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ABSTRACT: The oncogenic PI3K/Akt/mammalian target of rapamycin (mTOR) signaling axis and its downstream effector, the ribosomal protein S6 kinase 1 (S6K1) play a key role in mediating cell survival in various tumor cells. Here, we investigated the effects of brassinin (BSN), a phytoalexin first identified as a constituent of cabbage, on the PI3K/Akt/mTOR/S6K1 activation, cellular proliferation, and apoptosis in PC-3 human prostate cancer. BSN exerted a significant dose-dependent cytotoxicity and reduced constitutive phosphorylation of Akt against androgen-independent PC-3 cells as compared to androgen-dependent LNCaP cells. Moreover, knockdown of androgen receptor (AR) by small interfering RNA enhanced the potential effect of BSN on induction of apoptosis in LNCaP cells. BSN clearly suppressed the constitutive activation of PI3K/Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, TUNEL staining, loss of mitochondrial membrane potential, down-regulation of antiapoptotic and proliferative proteins, activation of caspase-3, and cleavage of PARP. Additionally, BSN could block broad-spectrum inhibition of PI3K/Akt/mTOR/S6K1 axes, and aberrant Akt activation by pcDNA3-myr-HA-Akt1 plasmid could not prevent the observed suppressive effect of BSN on constitutive mTOR activation. Finally, overexpression of Bcl-2 also attenuated BSN-mediated apoptosis in PC-3 cells. Taken together, our findings suggest that BSN can interfere with multiple signaling cascades involved in tumorigenesis and might be provided as a potential therapeutic candidate for both the prevention and treatment of prostate cancer. Copyright © 2013 John Wiley & Sons, Ltd.
Phytotherapy Research 05/2013; · 2.09 Impact Factor
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ABSTRACT: Elderly patients visiting pain clinic may be at greater risk of misunderstanding the explanation because of age-related cognitive decline. Video instruction may provide a consistent from of teaching in a visual and realistic manner. We evaluated the effect of educational video on the patient understanding and satisfaction in a group of geriatric patients visiting pain clinic.
Ninety two patients aged more than 60 years old who were scheduled for transforaminal epidural block were recruited. After exposure to either video or paper instruction process, each patient was asked 5-item comprehension questions, overall satisfaction and preference question. During follow-up period, number of outpatient referral-line call for further explanation was counted.
We observed significantly better comprehension in the video education compared with paper instruction (P < 0.001). Patient satisfaction was also higher in the video group (P = 0.015), and patients visiting pain clinic were more preferred video instruction (P < 0.001). Proportion of referral-line call for further explanation were similar (P = 0.302).
Video approach to instruction process before consent improves treatment comprehension in geriatric patient visiting pain clinic.
The Korean journal of pain 10/2012; 25(4):254-7.
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Seong Won Kim,
Sung-Moo Kim,
Hang Bae,
Dongwoo Nam,
Jun-Hee Lee,
Seok-Geun Lee,
Bum Sang Shim, Sung-Hoon Kim,
Kyoo Seok Ahn,
Seung-Hoon Choi,
Gautam Sethi,
Kwang Seok Ahn
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ABSTRACT: BACKGROUND: Akt/mTOR/S6K1 signaling cascades play an important role both in the survival and proliferation of tumor cells. METHODS: In the present study, we investigated the effects of embelin (EB), identified primarily from the Embelia ribes plant, on the Akt/mTOR/S6K1 activation, associated gene products, cellular proliferation, and apoptosis in human prostate cancer cells. RESULTS: EB exerted significant cytotoxic and suppressive effects on Akt and mTOR activation against androgen-independent PC-3 cells as compared to androgen-dependent LNCaP cells. Moreover, EB suppressed the constitutive activation of Akt/mTOR/S6K1 signaling cascade, which correlated with the induction of apoptosis as characterized by accumulation of cells in subG1 phase, positive Annexin V binding, down-regulation of anti-apoptotic (Bcl-2, Bcl-xL, survivin, IAP-1, and IAP-2) and proliferative (cyclin D1) proteins, activation of caspase-3, and cleavage of PARP. We also observed that EB can significantly enhance the apoptotic effects of a specific pharmacological Akt inhibitor when used in combination and also caused broad inhibition of all the three kinases in Akt/mTOR/S6K1 signaling axis in PC-3 cells. CONCLUSIONS: EB inhibits multiple signaling cascades involved in tumorigenesis and can be used as a potential therapeutic candidate for both the prevention and treatment of prostate cancer. Prostate © 2012 Wiley Periodicals, Inc.
The Prostate 08/2012; · 3.48 Impact Factor
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ABSTRACT: Context: Nobiletin is one of the citrus bioflavonoids and can be found in citrus fruits such as lemons, oranges, tangerines, and grapefruits. The most studied properties of nobiletin are its anti-inflammatory and anticancer activities. Objective: The exact mechanisms of how nobiletin inhibits tumor metastasis and invasion are still not fully understood. In this study, we screened various natural compounds to down-modulate the CXC chemokine receptor-4 (CXCR4) and matrix metallopeptidase-9 (MMP-9). Materials and methods: The effect of nobiletin on the constitutive expressions of CXCR4 and MMP-9, MMP-9 enzymatic activity, associated nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) activation, and tumor cell invasion in human breast cancer cells was investigated. CXCR4 and MMP-9 expression were evaluated via reverse transcription polymerase chain reaction (RT-PCR) and western blotting. NF-κB activation was also evaluated by electrophoretic mobility shift assay (EMSA). In addition, the antimetastatic effects of nobiletin were determined by gelatin zymography and invasion assay. Results: Nobiletin down-regulated both the constitutive expressions of CXCR4 and MMP-9 in human breast cancer cells with IC(50) values of 32 and 24 µM, respectively. Nobiletin also suppressed MMP-9 enzymatic activity and tumor cell invasion under noncytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the nobiletin-induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the down-regulation of CXCR4 and MMP-9 were at the transcriptional level, as indicated by the down-regulation of mRNA expression and the suppression of the constitutive NF-κB and MAPKs activation. Discussion and conclusion: Our results indicate, for the first time, that nobiletin is a novel blocker of CXCR4 and MMP-9 expressions and thus has the potential to suppress metastasis of breast cancer.
Pharmaceutical Biology 08/2012; 50(10):1210-8. · 0.88 Impact Factor
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Ki Dong Kim,
Hyun Jung Kim,
Kyung-Ran Park,
Sung-Moo Kim,
Yun-Cheol Na,
Bum Sang Shim, Sung-Hoon Kim,
Seung-Hoon Choi,
Kyoo Seok Ahn,
Seung-Hee Ryu,
Sang-wook Lee,
Kwang Seok Ahn
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ABSTRACT: Korean red pine (Pinus densiflora) bark extract is used for the treatment of chronic inflammatory-related ailments through as yet undefined mechanisms. The
present study was conducted to explore the anti-inflammatory activities of Korean red pine bark extract (commercially called
Pinexol in Korea) in murine RAW 264.7 macrophages and LPS-induced shock in mice. Here, we set out to determine whether the
anti-inflammatory effects of Pinexol are mediated to suppress nuclear factor-κB (NF-κB) activation in lipopolysaccharide (LPS)-stimulated
RAW 264.7 cells. We found that Pinexol significantly suppressed LPS-stimulated nitric oxide (NO) and IL-6 production without
affecting cell viability. Pinexol inhibited the expression of LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2
(COX-2) protein and their mRNA expression. As a result, Pinexol inhibited pro-inflammatory cytokines such as IL-6, which is
hypothesized as being due to the suppression of LPS-induced NF-κB activation. Moreover, Pinexol improved the survival rate
during lethal endotoxemia by inhibiting the production of TNF-α and IL-6 in an animal model and our GC-MS analysis using derivertization
showed that four major components of Pinexol were cathechin, epi-catechin, and methylated catechins. Therefore, we demonstrate
here the evidence that Korean red pine bark extract potentially inhibits the biomarkers related to inflammation in vitro and
in vivo, and might be provided as a potential candidate for treatment of inflammatory diseases.
KeywordsKorean red pine–NF-κB–MAPKs–Nitric oxide–Cyclooxygenase-2–Endotoxemia
Oriental Pharmacy and Experimental Medicine 04/2012; 11(1):61-70.
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ABSTRACT: Chrysanthemum indicum L. has been shown to possess antiinflammatory and anticancer activities, but its molecular targets/pathways are not yet fully understood in tumor cells. In the present study, the potential effects of C. indicum on signal transducer and activator of transcription 3 (STAT3) signaling pathway in different tumor cells were examined. The solvent fractions (hexane, CH(2) Cl(2) , EtOAc, and BuOH,) were obtained from a crude extract (80% EOH extract) of C. indicum. The methylene chloride fraction of C. indicum (MCI) exhibited strong cytotoxic activity as compared with the other fractions and clearly suppressed constitutive STAT3 activation against both DU145 and U266 cells, but not MDA-MB-231 cells. The suppression of constitutive STAT3 activation by MCI is associated with blocking upstream JAK1 and JAK2, but not Src. MCI downregulated the expression of STAT3-regulated gene products; this is correlated with the accumulation of the cell cycle at sub-G1 phase, the induction of caspase-3 activation, and apoptosis. Moreover, the major components of the MCI were bioactive compounds such as sudachitin, hesperetin, chrysoeriol, and acacetin. Sudachitin, chrysoeriol, and acacetin also exerted significantly cytotoxicity, clearly suppressed constitutive STAT3 activation, and induced apoptosis, although hesperetin did not show any significant effect in DU145 cells. Overall, our results demonstrate that MCI could induce apoptosis through inhibition of the JAK1/2 and STAT3 signaling pathways. Copyright © 2012 John Wiley & Sons, Ltd.
Phytotherapy Research 03/2012; · 2.09 Impact Factor
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Nae Hyung Ryu,
Kyung-Ran Park,
Sung-Moo Kim,
Hyung-Mun Yun,
Dongwoo Nam,
Seok-Geun Lee,
Hyeung-Jin Jang,
Kyoo Seok Ahn, Sung-Hoon Kim,
Bum Sang Shim,
Seung-Hoon Choi,
Ashik Mosaddik,
Somi K Cho,
Kwang Seok Ahn
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ABSTRACT: This study was carried out to evaluate the anticancer effects of guava leaf extracts and its fractions. The chemical compositions of the active extracts were also determined. In the present study, we set out to determine whether the anticancer effects of guava leaves are linked with their ability to suppress constitutive AKT/mammalian target of rapamycin (mTOR)/ribosomal p70 S6 kinase (S6K1) and mitogen-activated protein kinase (MAPK) activation pathways in human prostate cancer cells. We found that guava leaf hexane fraction (GHF) was the most potent inducer of cytotoxic and apoptotic effects in PC-3 cells. The molecular mechanism or mechanisms of GHF apoptotic potential were correlated with the suppression of AKT/mTOR/S6K1 and MAPK signaling pathways. This effect of GHF correlated with down-regulation of various proteins that mediate cell proliferation, cell survival, metastasis, and angiogenesis. Analysis of GHF by gas chromatography and gas chromatography-mass spectrometry tentatively identified 60 compounds, including β-eudesmol (11.98%), α-copaene (7.97%), phytol (7.95%), α-patchoulene (3.76%), β-caryophyllene oxide (CPO) (3.63%), caryophylla-3(15),7(14)-dien-6-ol (2.68%), (E)-methyl isoeugenol (1.90%), α-terpineol (1.76%), and octadecane (1.23%). Besides GHF, CPO, but not phytol, also inhibited the AKT/mTOR/S6K1 signaling pathway and induced apoptosis in prostate cancer cells. Overall, these findings suggest that guava leaves can interfere with multiple signaling cascades linked with tumorigenesis and provide a source of potential therapeutic compounds for both the prevention and treatment of cancer.
Journal of medicinal food 03/2012; 15(3):231-41. · 1.39 Impact Factor
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ABSTRACT: Emodin (ED), an anthraquinone derivative, has been found to inhibit proliferation, induce apoptosis, suppress angiogenesis, impede metastasis, and enhance chemotherapy. However, the detailed mechanism of ED related to the regulation of CXC chemokine receptor-4 (CXCR4) gene expression that affects cellular migration and invasion in prostate and lung cancer cells are not fully understood. Recent evidence indicates that the CXCR4/CXCL12 axis is involved in promoting invasion and metastasis in tumors. Thus, novel agents that can downregulate CXCR4 expression have therapeutic potential in repressing cancer metastasis. Among ED and its derivatives, it is found that ED downregulated the expression of both CXCR4 and HER2 without affecting cell viability in tumor cells. The suppression of CXCR4 expression by ED was found to correlate with the inhibition of CXCL12-induced migration and invasion of both DU145 and A549 cells. Besides, neither proteasome inhibition nor lysosomal stabilization had any effect on ED-induced decrease in CXCR4 expression. The basic molecular mechanisms unveiled that the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression and suppression of NF-κB activation. Overall, our findings suggest that ED is a novel blocker of CXCR4 expression and, thus, has enormous potential as a powerful therapeutic agent for metastatic cancer.
Immunopharmacology and Immunotoxicology 02/2012; 34(5):768-78. · 1.83 Impact Factor
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Shu Yuan Chiang,
Sung-Moo Kim,
Chulwon Kim,
Jae-Young Um,
Kyung-Ran Park,
Seong Won Kim,
Seok-Geun Lee,
Hyeung-Jin Jang,
Dongwoo Nam,
Kyoo Seok Ahn, Sung-Hoon Kim,
Seung-Hoon Choi,
Bum Sang Shim,
Yun-Cheol Na,
Eun-Kyung Jeong,
Somi K Cho,
Kwang Seok Ahn
[show abstract]
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ABSTRACT: Although Dangyuja (Citrus grandis Osbeck) exhibits anti-inflammatory and anticancer activities, its molecular targets and pathways, especially in human prostate cancer cells, are not fully understood. In this study, the antiproliferative effect of Dangyuja leaves through the signal transducer and activator of transcription (STAT) 3 signaling pathway was investigated in human prostate carcinoma DU145 cells. The solvent fractions (n-hexane, chloroform, ethyl acetate, and n-butanol) were obtained from a crude extract (80% methanol extract) of Dangyuja leaves. We first found that the chloroform fraction of Dangyuja leaves (DCF) was the most cytotoxic against DU145 cells. DCF inhibited constitutive STAT3 activation through blocking upstream Janus-like kinase 2 and c-Src. Consistent with STAT3 inactivation, DCF down-regulated the expression of STAT3 target genes, including bcl-2, bcl-xl, and cyclin D1; this correlated with the suppression of proliferation, the accumulation of cell cycle at the sub-G(1) phase, and the induction of apoptosis. Furthermore, DCF exerted a relatively minor effect on the growth of human prostate noncancerous RWPE-1 cells. Nobiletin, a major active constituent of DCF, could induce apoptosis via the suppression of constitutive STAT3 activation. Overall, our results indicate that the anti-inflammatory and anticancer activities previously assigned to DCF may be mediated partially through the suppression of the STAT3 signaling.
Journal of medicinal food 02/2012; 15(2):152-60. · 1.39 Impact Factor
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ABSTRACT: Lumbar spinal stenosis is a commonly treated with epidural injections of local anesthetics and corticosteroids, however, these therapies may relieve leg pain for weeks to months but do not influence functional status. Furthermore, the majority of patients report no substantial symptom change over the repeated treatment. Utilizing balloon catheters, we successfully treated with three patients who complained persistent symptoms despite repeated conventional steroid injections. Our results suggest that transforaminal decompression using a balloon catheter may have potential in the nonsurgical treatment of spinal stenosis by modifying the underlying pathophysiology.
The Korean journal of pain 01/2012; 25(1):55-9.
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ABSTRACT: Spinal nerve ligation (SNL) injury in rats produces a pain syndrome that includes mechanical and thermal allodynia. Previous studies have indicated that proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) play an important role in peripheral mediation of neuropathic pain, and that altered dorsal root ganglion (DRG) function and degree of DRG neuronal apoptosis are associated with spinal nerve injury. The present study was conducted to evaluate the expression of TNF-α and the extent of apoptosis in the dorsal root ganglion after SNL in rats.
Sprague-Dawley rats were subjected to SNL of the left L5 and L6 spinal nerves distal to the DRG and proximal to the formation of the sciatic nerve. At postoperative day 8, TNF-α protein levels in the L5-6 DRG were compared between SNL and naive groups using ELISA. In addition, we compared the percentage of neurons injured in the DRG using immunostaining for apoptosis and localization of activated caspase-3.
SNL injury produced significant mechanical and cold allodynia throughout the 7-day experimental period. TNF-α protein levels were increased in the DRG in rats that had undergone SNL (12.7 ± 3.2 pg/100 µg, P < 0.001) when compared with naïve rats (4.1 ± 1.4 pg/100 µg). The percentage of neurons or satellite cells co-localized with activated caspase-3 were also significantly higher in rats with SNL than in naïve rats (P < 0.001, P < 0.05, respectively).
SNL injury produces mechanical and cold allodynia, as well as TNF-α elevation and apoptosis in the DRG.
The Korean journal of pain 12/2011; 24(4):185-90.
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Ji Young Heo,
Hyun Jung Kim,
Sung-Moo Kim,
Kyung-Ran Park,
Sang-Yoon Park,
Seong Won Kim,
Dongwoo Nam,
Hyeung-Jin Jang,
Seok-Geun Lee,
Kyoo Seok Ahn, Sung-Hoon Kim,
Bum Sang Shim,
Seung-Hoon Choi,
Kwang Seok Ahn
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ABSTRACT: Even though embelin, an inhibitor of the XIAP, is known to exhibit anti-inflammatory and anti-cancer activities, very little is known about its mechanism of action. Here, we investigated whether embelin mediates its effect through interference with the signal transducer and activator of transcription 3 (STAT3) pathway. We found that embelin inhibited constitutive STAT3 activation in a variety of human cancer cell lines such as U266, DU-145, and SCC4 cells. The suppression of STAT3 was mediated through inhibition of the activation of JAK2 and c-Src. Pervanadate treatment also reversed the embelin-induced down-regulation of STAT3, suggesting the involvement of a protein tyrosine phosphatase. Indeed, we found that embelin-induced the expression of the tyrosine phosphatase PTEN and deletion of the PTEN gene by small interfering RNA abolished the ability of embelin to inhibit STAT3 activation. Besides, embelin failed to suppress STAT3 activation in PTEN-null PC3 cells, thus indicating that the inhibitory effect of embelin on STAT3 is PTEN-dependent. Embelin down-regulated the expression of STAT3-regulated gene products; this correlated with the suppression of cell proliferation and invasion, and the induction of apoptosis through the activation of caspase-3. Overall, our results indicate that the anti-inflammatory and anti-cancer activities previously assigned to embelin may be mediated in part through the suppression of the STAT3 pathway.
Cancer letters 09/2011; 308(1):71-80. · 4.86 Impact Factor
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Eun-Jung Lee,
Chulwon Kim,
Jin-Young Kim,
Sung-Moo Kim,
Dongwoo Nam,
Hyeung-Jin Jang, Sung-Hoon Kim,
Bum Sang Shim,
Kyoo Seok Ahn,
Seung-Hoon Choi,
Sang Hoon Jung,
Kwang Seok Ahn
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ABSTRACT: Patrinia scabiosaefolia (PS) has been used for curing various types of inflammatory-related disorders. However, the precise mechanism of the anti-inflammatory activity of PS remains unclear. Here, we investigated the anti-inflammatory effects of several fractions isolated from the PS in RAW 264.7 macrophages. The results indicated that the ethyl acetate fraction of PS (EAPS) concentration highly suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) and IL-6 productions without a cytotoxic effect on RAW 264.7 cells. EAPS inhibited the expressions of LPS-induced iNOS and COX-2 protein and their mRNA in a dose-dependent manner. Particularly, EAPS suppressed the level of nuclear factor-κB (NF-κB) activity, which was linked with the suppression of LPS-induced phosphorylation of p65 at serine 276 and p65 translocation into nuclei, but not MAPK signaling. In addition, treatment with EAPS inhibited the production of TNF-α in LPS-injected mice and suppressed the production of IL-6 and TNF-α in LPS-stimulated splenocytes from BALB/c mice. Therefore, we demonstrate here that Patrinia scabiosaefolia potentially inhibits the biomarkers related to inflammation through the blocking of NF-κB p65 activation, and it may be a potential therapeutic candidate for the treatment of inflammatory diseases.
Immunopharmacology and Immunotoxicology 08/2011; 34(2):282-91. · 1.83 Impact Factor
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ABSTRACT: Facet joint disease plays a major role in axial low-back pain. Few diagnostic tests and imaging methods for identifying this condition exist. Single photon emission computed tomography (SPECT) is reported that it has a high sensitivity and specificity in diagnosing facet disease. We prospectively evaluated the use of bone scintigraphy with SPECT for the identification of patients with low back pain who would benefit from medial branch block.
SPECT was performed on 33 patients clinically suspected of facet joint disease. After SPECT, an ultrasound guided medial branch block was performed on all patients. On 28 SPECT-positive patients, medial branch block was performed based on the SPECT findings. On 5 negative patients, medial branch block was performed based on clinical findings. For one month, we evaluated the patients using the visual analogue scale (VAS) and Oswestry disability index. SigmaStat and paired t-tests were used to analyze patient data and compare results.
Of the 33 patients, the ones who showed more than 50% reduction in VAS score were assigned 'responders'. SPECT positive patients showed a better response to medial branch blocks than negative patients, but no changes in the Oswestry disability index were seen.
SPECT is a sensitive tool for the identification of facet joint disease and predicting the response to medial branch block.
The Korean journal of pain 06/2011; 24(2):81-6.
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ABSTRACT: Recent reports have indicated that decursin can induce apoptosis, suppress tumor growth, and inhibit angiogenesis. In this experiment, we investigated how decursin could potentiate the cytotoxic effects of bortezomib in human multiple myeloma cells. We found that decursin inhibited cell viability in U266, MM.1S and ARH77 cells, but not in peripheral blood mononuclear cells (PBMC). Decursin-induced apoptosis through the activation of caspase-8, -9, and -3 in U266 cells. This correlated with the down-regulating of cyclin D1, bcl-2, bcl-xL, survivin, and the vascular endothelial growth factor (VEGF), which are all regulated by the activation of signal transducers and the activator of transcription 3 (STAT3). Indeed, decursin inhibited constitutive STAT3 activation through inhibition of the activation of Janus-activated kinase 2 (JAK2) in U266 cells. In addition, decursin inhibited interleukin-6-inducible STAT3 activation in a time-dependent manner in MM.1S cells. Interestingly, decursin significantly potentiated the apoptotic effects of bortezomib in U266 cells. These effects of decursin were correlated with the suppression of constitutive STAT3 activation in U266 cells. Overall, these results suggest that decursin is a novel blocker of STAT3 activation and it may be a potential candidate for overcoming chemo-resistance through suppression of this signaling.
Cancer letters 02/2011; 301(1):29-37. · 4.86 Impact Factor
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Jung Il Lee,
Young Wan Ha,
Tae Won Choi,
Hyun Jung Kim,
Sung-Moo Kim,
Hyeung-Jin Jang,
Jung-Hye Choi,
Man Ho Choi,
Bong Chul Chung,
Gautam Sethi, Sung-Hoon Kim,
Kyoo Seok Ahn,
Seung-Hoon Choi,
Bum Sang Shim,
Kwang Seok Ahn
[show abstract]
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ABSTRACT: Panax ginseng has been reported to have cancer-preventive properties and, through anti-inflammatory, antioxidant, and pro-apoptotic mechanisms, to influence gene expression. However, the comparison of Korean white ginseng (WG) and red ginseng (RG) in their apoptotic effects and the identification of the selective cellular uptake of the ginsenosides in human breast cancer cells have not yet been fully understood. In the present study, the relative nonpolar and protopanaxadiol (PPD) class ginsenosides exhibited more cytotoxic and efficient cellular uptake on MCF-7 cells compared with the relative polar and protopanaxatriol (PPT) class compounds. PPD class ginsenosides were present in RG in a 2.5 times higher concentration as compared to WG, while PPT class ginsenosides were only present in WG. Thus, RG exerted more potent cytotoxicity than WG against MCF-7 and MDA-MB231 cells. RG also increased the sub-G1 DNA contents of the cell cycle and Annexin V-positive apoptotic bodies undergoing apoptosis through the caspase-3 activation in MCF-7 cells. In addition, RG downregulated the proliferative and anti-apoptotic gene products and potentiated paclitaxel-induced apoptosis in MCF-7 cells. Overall, RG contained a higher concentration of PPD class ginsenosides as compared to WG; the greater cellular uptake of PPD resulted in more substantial antiproliferative activity in human breast cancer cells.
Planta Medica 01/2011; 77(2):133-40. · 2.15 Impact Factor
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Hyoung Joo Lee,
Tae Won Choi,
Hyun Jung Kim,
Dongwoo Nam,
Sang Hoon Jung,
Eun Ha Lee,
Hee Ju Lee,
Eun Myoung Shin,
Hyeung-Jin Jang,
Kyoo Seok Ahn,
Bum Sang Shim,
Seung-Hoon Choi, Sung-Hoon Kim,
Gautam Sethi,
Kwang Seok Ahn
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ABSTRACT: Angelica keiskei has been shown to exhibit antitumor, antioxidant, and antidiabetic activities, and the fresh leaves and dry powder are used for health food. In spite of several beneficial effects, however, the molecular mechanism or mechanisms behind anti-inflammatory activities of A. keiskei remain unclear. Thus, we investigated the effects of A. keiskei on the activities of inducible nitric oxide (NO) synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. We found that the n-hexane fraction of A. keiskei (HAK) significantly inhibited LPS-induced NO and prostaglandin E(2) production and tumor necrosis factor-alpha secretion. HAK also inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNA levels. Furthermore, we hypothesize that anti-inflammatory effects by HAK can be linked to interference with the signaling pathway of mitogen-activated protein kinases (MAPKs) and the activation pathway of nuclear factor kappaB (NF-kappaB). HAK suppressed LPS-induced c-Jun NH(2)-terminal kinase, p38, and p44/p42 MAPK activation. We also found that the cell-based assay system showed that HAK suppressed LPS-induced NF-kappaB activity in transfectant RAW 264.7 cells. In addition, the electrophoretic mobility shift assay showed the same result as in the cell-based assay system. Our data suggest that the anti-inflammatory effect of HAK is mediated through down-modulation of iNOS and COX-2 gene products by blocking the signaling pathways of MAPKs and NF-kappaB.
Journal of medicinal food 06/2010; 13(3):691-9. · 1.39 Impact Factor
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Jung-Hoon Lee,
Hyo-Jeong Lee,
Chan-Hee Lee,
Hyo-Jung Lee,
Hyunsoo Bae,
Sung-Moo Kim,
Sun-Hee Kim,
Wonil Koh,
Wan-Seok Kim,
Kwang Seok Ahn,
Seung-Hoon Choi,
Namin Baek, Sung-Hoon Kim
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ABSTRACT: Hwaeumjeon is a classical prescription that has been traditionally used for treatment of urogenital diseases with no scientific evidences until now. Thus, the present study was performed to evaluate antitumor mechanism of ethanolic Hwaeumjeon (EHEJ). 2-Dimensional electrophoresis (2-DE) proteomic analysis, cell culture study, and Western blotting on apoptosis and prostate-specific antigen (PSA) related proteins were carried out in LNCaP prostate cancer cells. Eight spots with significant increased or decreased expression revealed by 2-DE based comparative proteomic analysis were identified as an increased protein ENC-1AS, four decreased proteins such as RAB34, SFRS1, heat shock 27, and proteasome activator, and three novel proteins such as Rho GDP dissociation inhibitor alpha, cytoplasmic antiproteinase, and EIF3EIP protein in EHEJ-treated LNCaP cells. In addition, EHEJ selectively inhibited the growth of LNCaP prostate cancer cells compared to normal human umbilical vein endothelial cells. Furthermore, EHEJ inhibited PSA and androgen receptor (AR) expression in androgen sensitive LNCaP prostate cancer cells at nontoxic concentrations. Also, EHEJ increased sub-G1 apoptotic portion, activated caspase-9 and -3, cleaved poly (ADP-ribose) polymerase (PARP) and increased the ratio of Bax to Bcl-2. Interestingly, EHEJ also attenuated phosphatidylinositol-3 kinase (PI3K) expression and suppressed the phosphorylation of survival gene AKT, ERK, and HSP27 in LNCaP cells. Consistently, PI3K and ERK inhibitors potentiated EHEJ-induced cytotoxicity and overexpression of Bcl-2 attenuated EHEJ-mediated apoptosis in LNCaP cells. These findings suggest that EHEJ induces mitochondrial dependent apoptosis partly via PI3K/AKT/HSP27/ERK pathways and inhibits PSA and AR in LNCaP cells as a prostate cancer chemopreventive candidate.
Environmental Toxicology and Pharmacology 07/2009; 28(1):78-85. · 1.47 Impact Factor
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ABSTRACT: This study was designed to evaluate the effect of Hand acupuncture treatment on the stress urinary incontinence of 52 women randomly assigned to Experimental hand acupuncture treatment group (n = 25) and Control group (n = 27). 11 hand acupuncture points were established as a basic treatment formula. Among them, 5 points on the midline of the palm represent the major acupoints of external genitals, bladder, abdominal aorta, stomach and heart, while the other 6 points were applied as supplementary ones (2 points on the mid line of the palm for adrenal glands and heart, 2 points near the wrist for kidneys and 2 points on the back of the hand for bladder). This basic treatment formula was applied to all subjects in the Experimental group. Additional treatments were given to the subjects with tenderness at ST27, CV4 or SP15, while no treatment to the subjects in Control group for 12 weeks. Assessment was made before and after 12 weeks of clinical study. In the present study, Hand acupuncture treatment significantly reduced the frequency of urinary incontinence compared to Control group. Similarly, the prevalence score of urinary incontinence was significantly reduced up to 37% of Control group in Experimental group. Furthermore, vaginal contraction pressure of the Experimental group was significantly increased 1.6 fold compared to Control group. In addition, Hand acupuncture treatment significantly improved the scores of making friends, sexual life and social community in Experimental group compared to Control group. Overall, these findings suggest that Hand acupuncture can be a potent alternative therapy for stress urinary incontinence.
Acupuncture & electro-therapeutics research 02/2008; 33(3-4):179-92. · 1.30 Impact Factor
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ABSTRACT: Topochemical photoreaction of bis(phenylethenyl)-dicyanopyrazines (1) was conducted in solution, in the vapor deposited thin film, and in the single crystals. Compound 1 showed the crystal morphology to give the yellow and orange colored crystals. The difference in crystal structures of yellow and orange crystals was confirmed with X-ray crystal analysis which revealed that the orange one was contracted in the crystallographic c-axis by 0.11 Å than that of the yellow one at the same temperature. The physical property and photoreactivity of two crystals were explained with the topochemical control and lattice contraction.
Dyes and Pigments.
