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ABSTRACT: Six compounds were isolated from the twigs ofIlex macropoda. Their structures were elucidated as betulinic acid, lupeol, betulone, betulin, erythrodiol and 11-oxo-erythrodiol
by physicochemical and spectroscopic analysis. Among them, lupeol, betulone, erythrodiol and 11-oxo-erythrodiol were isolated
for the first time from this plant.
Archives of Pharmacal Research 04/2012; 25(5):617-620. · 1.59 Impact Factor
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ABSTRACT: The methanolic extract of the leaves ofLiriodendron tulipifera was found to show inhibitory activity towards farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the
methanolic extract resulted in the isolation of lipiferolide, an inhibitor of FPTase. This compound inhibited the FPTase activity
in a dose-dependent manner, and showed cell growth inhibitory activity against several tumor cells.
Archives of Pharmacal Research 04/2012; 30(3):299-302. · 1.59 Impact Factor
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ABSTRACT: cis-Hinokiresinol, also known as (+)-nyasol, was isolated for the first time from an aquatic herbaceous plant,Trapa pseudoincisa NAKAI, via silica gel and octadecyl silica gel column chromatographies. The chemical structure was determined via analyses
of the spectroscopic data, including NMR, MS and IR. cis-Hinokiresinol was also found to exhibit antioxidant and antiatherogenic
activities. The IC50 values for the scavenging activities of cis-hinokiresinol on ABTS cation and superoxide anion radicals were 45.6 and 40.5
μM, respectively. The IC50 values for the inhibitory effects on Lp-PLA2, hACAT1, hACAT2 and LDL-oxidation were 284.7, 280.6, 398.9 and 5.6 μM, respectively.
Archives of Pharmacal Research 04/2012; 30(11):1392-1397. · 1.59 Impact Factor
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Jae Hyeok Lee,
Nam-In Baek,
Sung-Hoon Kim,
Hee Wook Park,
Jae Heon Yang,
Jeong Joo Lee,
Seong Jin Kim,
Seung il Jeong,
Chan-Ho Oh,
Kyu-Hee Lee, Dae Keun Kim
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ABSTRACT: We have isolated a new prenylated chalcone from the roots of Sophora flavescens (Leguminosae). We determined that structure
of this compound is 7,9,2’,4’-tetrahydroxy-8-isopentenyl-5-methoxychalcone (1) on the basis of spectroscopic analysis (1D
and 2D NMR data). Compound 1 exhibited potent cytotoxicity against human acute promyelocytic (HL60), mouse lymphocytic (L1210)
and human histiocytic (U937) leukemia cells.
Archives of Pharmacal Research 04/2012; 30(4):408-411. · 1.59 Impact Factor
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ABSTRACT: A new compound 2 and two known guaiane-type sesquiterpenoids were isolated from the methylene chloride-soluble fraction of
the methanolic extract of the fruits ofTorilis japonica (Umbelliferae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated
as torilin (1), 11-acetoxy-8-angeloyloxy-1β-hydroxy-4-guaien-3-one (1β-hydroxytorilin,2) and 11-acetoxy-8-angeloyloxy-1α-hydroxy-4-guaien-3-one (1α-hydroxytorilin,3) by spectroscopic analysis. Compounds1–3 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.
Archives of Pharmacal Research 04/2012; 29(2):131-134. · 1.59 Impact Factor
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ABSTRACT: The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937.
Icariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-x(L) and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells.
Our results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.
PLoS ONE 01/2012; 7(4):e28706. · 4.09 Impact Factor
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ABSTRACT: Anthraquinones have been reported as phosphatase inhibitors. Therefore, anthraquinone derivatives were screened to identify a potent phosphatase inhibitor against the phosphatase of regenerating liver-3 (PRL-3). Emodin strongly inhibited phosphatase activity of PRL-3 with IC(50) values of 3.5μM and blocked PRL-3-induced tumor cell migration and invasion in a dose-dependent manner. Emodin rescued the phosphorylation of ezrin, which is a known PRL-3 substrate. The results of this study reveal that emodin is a PRL-3 inhibitor and a good lead molecule for obtaining a selective PRL-3 inhibitor.
Bioorganic & medicinal chemistry letters 11/2011; 22(1):323-6. · 2.65 Impact Factor
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ABSTRACT: The leaves of Eriobotrya japonica Lindl. have been widely used as a traditional medicine for the treatment of many diseases including gastroenteric disorders, diabetes mellitus, chronic bronchitis and asthma. In the present study, the anti-metastatic action of the EtOAc fraction of the leaves of E. japonica (LEJ) was investigated. LEJ showed potent inhibitory effects on MMP-2 and MMP-9 activities and expressions via down-regulation of NF-κB translocation to the nucleus in B16F10 cells. In addition, the cell migration and invasion were down-regulated by LEJ. LEJ also significantly suppressed lung metastasis in vivo. Moreover, we isolated the compounds ursolic acid and 2α-hydroxyursolic acid from LEJ and both compounds also significantly suppressed MMP-2 and MMP-9 activities, indicating that they are the active components of LEJ. The present results demonstrate that LEJ may be used as valuable antimetastatic agent for the treatment of cancer metastasis.
Archives of Pharmacal Research 03/2011; 34(3):425-36. · 1.59 Impact Factor
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Sun-Hee Kim,
Kwang Seok Ahn,
Soo-Jin Jeong,
Tae-Rin Kwon,
Ji Hoon Jung,
Sun-Mi Yun,
Ihn Han,
Seok-Geun Lee, Dae Keun Kim,
Minkyung Kang,
Chang-Yan Chen,
Jung Weon Lee,
Sung-Hoon Kim
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ABSTRACT: Although the flavonoid icariside II exhibits anti-inflammatory and anti-cancer activities, its molecular targets/pathways in human multiple myeloma cells are poorly understood. To analyze the effects on signal transducer and activator of transcription 3 (STAT3) signaling and apoptosis, U266 multiple myeloma cells were treated with icariside II and performed Western blotting, electrophoretic mobility gel shift assay (EMSA), RT-PCR, proliferation assay, cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Icariside II inhibited STAT3 activation and enhanced the expression of SHP-1 and PTEN through inhibiting Janus activated kinase 2 (JAK2) and c-Src. Icariside II down-regulated the expression of STAT3 target genes Bcl-2, Bcl-x(L), survivin, cyclin D(1), COX-2 and vascular endothelial growth factor (VEGF). Also, icariside II enhanced poly (ADP-ribose) polymerase (PARP) cleavage and caspase-3 activation. Pervanadate reversed the icariside II-mediated STAT3 inactivation and also blocked the cleavages of caspase-3 and PARP, suggesting involvement of STAT3 pathway in icariside II-induced apoptosis. Furthermore, icariside II enhanced the apoptotic effects of clinically used drugs thalidomide and bortezomib in U266 cells. Icariside II could be a potential therapeutic intervention agent alone or in combination with current drugs for multiple myeloma as a novel blocker of STAT3 signaling cascades at multiple levels, contributing to its anti-proliferative and anti-apoptosis.
European journal of pharmacology 03/2011; 654(1):10-6. · 2.59 Impact Factor
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Eun Jeong Choo,
Yun-Hee Rhee,
Soo-Jin Jeong,
Hyo-Jung Lee,
Hyun Seok Kim,
Hyun Suk Ko,
Ji-Hyun Kim,
Tae-Rin Kwon,
Ji Hoon Jung,
Jin Hyoung Kim,
Hyo-Jeong Lee,
Eun-Ok Lee, Dae Keun Kim,
Chang-Yan Chen,
Sung-Hoon Kim
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ABSTRACT: Anethole is known to possess anti-inflammatory and anti-tumor activities and to be a main constituent of fennel, anise, and camphor. In the present study, we evaluated anti-metastatic and apoptotic effects of anethole on highly-metastatic HT-1080 human fibrosarcoma tumor cells. Despite weak cytotoxicity against HT-1080 cells, anethole inhibited the adhesion to Matrigel and invasion of HT-1080 cells in a dose-dependent manner. Anethole was also able to down-regulate the expression of matrix metalloproteinase (MMP)-2 and -9 and up-regulate the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1. The similar inhibitory effect of anethole on MMP-2 and -9 activities was confirmed by zymography assay. Furthermore, anethole significantly decreased mRNA expression of urokinase plasminogen activator (uPA), but not uPA receptor (uPAR). In addition, anethole suppressed the phosphorylation of AKT, extracellular signal-regulated kinase (ERK), p38 and nuclear transcription factor kappa B (NF-κB) in HT-1080 cells. Taken together, our findings indicate that anethole is a potent anti-metastatic drug that functions through inhibiting MMP-2/9 and AKT/mitogen-activated protein kinase (MAPK)/NF-κB signal transducers.
Biological & Pharmaceutical Bulletin 01/2011; 34(1):41-6. · 1.66 Impact Factor
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ABSTRACT: The methanolic extract of the roots of Rubia akane (Rubiaceae) was found to show inhibitory activity on phosphatase of regenerating liver-3 (PRL-3). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two anthraquinone compounds, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6'-O-acetyl)-α-rhamnosyl(1→2)-β-glucoside and 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone, as inhibitors on PRL-3. These compounds inhibited PRL-3 in a dose-dependent manner with IC₅₀ values of 5.2 and 1.3 μg/mL, respectively.
Archives of Pharmacal Research 11/2010; 33(11):1747-51. · 1.59 Impact Factor
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ABSTRACT: The present study was conducted to investigate the effects of Baicalein (BE), which is hydrolyzed product of Baicalin (BA), on atopic dermatitis (AD). AD was induced in NC/Nga mice by DPE treatment. BE hydrogels treatment reduced the levels of skin severity scores. BE hydrogels treatment also decreased inflammatory cytokines such as TNF-alpha, IL-6, and its level in the serum. BE hydrogels treatment elevated IFN-gamma level in the spleenocyte culture supernatant. Cell numbers in the skin positive to CD3+/CD69+, CCR3+, CD11b+/Gr-1+, B220+/IgE+ all of which were up-regulated in AD-induced mice were decreased and returned to normal levels. Histological examination showed that infiltration levels of immune cells in the skin of AD-induced NC/Nga mice were much improved by BE hydrogels treatment. These results thus suggest that BE can regulate molecular mediators and immune cells that are functionally associated with atopic dermatitis induced in NC/Nga mice, and may play an important role in recovering AD symptoms.
International immunopharmacology 09/2010; 10(9):1142-8. · 2.21 Impact Factor
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ABSTRACT: Mast cell-mediated allergic disease is involved in many diseases such as anaphylaxis, rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of the water extract of Clinopodium gracile Matsum var. multicaule (WECG) on the mast cell-mediated allergic inflammation and studied the possible mechanism of action. WECG inhibited compound 48/80-induced systemic anaphylaxis and immunoglobulin E-mediated cutaneous anaphylaxis in a dose-dependent manner. WECG dose-dependently reduced histamine release from rat peritoneal mast cells and human mast cells. The inhibitory effect of WECG on histamine release was mediated by the modulation of intracellular calcium. In addition, WECG attenuated the phorbol 12-myristate 13-acetate and calcium ionophore A23187-stimulated gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 in human mast cells. The inhibitory effect of WECG on these proinflammatory cytokines was nuclear factor-kappaB (NF-kappaB) dependent. Our findings provide evidence that WECG inhibits mast cell-derived allergic inflammation and involvement of calcium and NF-kappaB in these effects.
Experimental Biology and Medicine 05/2010; 235(5):606-13. · 2.64 Impact Factor
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ABSTRACT: We recently reported the inhibitory effect of an oral administration of a Sophora flavescens Aiton methanol extract on the development of atopic dermatitis in the NC/Nga model mice. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. The aim of this study was to investigate the possible mechanism by which prenylated chalcone (PC, 7,9,2',4'-tetrahydroxy-8-isopentenyl-5-methoxychalcone), a natural product isolated from S. flavescens, inhibited cytokine-induced Th2 chemokine expression in human keratinocytes, HaCaT cells. The level of chemokine expression was measured by reverse transcription-polymerase chain reaction and HO-1 study was performed by Western blot analysis. Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha)-induced thymus- and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), cutaneous T-cell attracting chemokine (CTACK/CCL27) expression in a dose-dependent manner. Interestingly, PC significantly suppressed IFN-gamma and TNF-alpha-induced TARC/CCL17, MDC/CCL22 and CTACK/CCL27 expression via the induction of heme oxygenase (HO)-1. This suppression was completely restored by HO-1 siRNA, suggesting a direct role of HO-1 for the suppressive effect. Furthermore, exogenous CO, but not other end products of HO-1 activity, also suppressed IFN-gamma and TNF-alpha-induced TARC/CCL17, MDC/CCL22 and CTACK/CCL27 expression. These results demonstrate that prenylated chalcone induces HO-1 expression, which in turn HO-1 and/or CO suppresses Th2 chemokine expressions induced by cytokines in human HaCaT cells.
Archives of Pharmacal Research 05/2010; 33(5):753-60. · 1.59 Impact Factor
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Chan-Ho Oh,
Nam-Seok Kim,
Jae Heon Yang,
Hyunjin Lee,
Seokwon Yang,
Saerom Park,
Un-Ki So,
Jin-Beom Bae,
Jae Soon Eun,
Hoon Jeon,
Jong Pil Lim,
Jin Kwon,
Young-Suk Kim,
Tae Yong Shin, Dae Keun Kim
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ABSTRACT: Three compounds were isolated from the ethyl acetate soluble fraction of the methanolic extract of the leaves of Catalpa ovata (Bignoniaceae) through repeated column chromatography. We investigated the effects of these compounds on T cell-mediated responses for tumor surveillance and proliferation in U937, HL60, and Molt-4 leukemia cells. Compounds 1-3 inhibited proliferation of those cells in a dose-dependent manner. Compound 3 showed mild effect in Molt-4 cell cytotoxicity. Compound 3 enhanced gene expressions of p53 and IL-4, but decreased IL-2 and IFN-Gamma genes in Molt-4 cell. Our findings indicate that compound 3 may enhance T cell-mediated immune responses and anticancer properties.
Archives of Pharmacal Research 04/2010; 33(4):545-50. · 1.59 Impact Factor
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ABSTRACT: A new (3) and three known germacrane-type sesquiterpenoids were isolated from the chloroform-soluble fraction of the methanolic extract of the bark of Magnolia kobus (Magnoliaceae) through repeated silica gel and Sephadex LH-20 column chromatography. Their chemical structures were elucidated as costunolide (1), parthenolide (2), isobisparthenolidine (3), and bisparthenolidine (4) by spectroscopic analysis. Compounds 1-4 exhibited cytotoxicity against human A549, SK-OV-3, SK-MEL-2, and HCT15 tumor cells.
Archives of Pharmacal Research 01/2010; 33(1):71-4. · 1.59 Impact Factor
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Young Ran Park,
Jae Soon Eun,
Hwa Jung Choi,
Manoj Nepal, Dae Keun Kim,
Seung-Yong Seo,
Rihua Li,
Woo Sung Moon,
Nam-Pyo Cho,
Sung-Dae Cho,
Tae Sung Bae,
Byung Il Kim,
Yunjo Soh
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ABSTRACT: Osteoclasts, derived from multipotent myeloid progenitor cells, play homeostatic roles in skeletal modeling and remodeling, but may also destroy bone in pathological conditions such as osteoporosis and rheumatoid arthritis. Osteoclast development depends critically on a differentiation factor, the receptor activator of NF-kappaB ligand (RANKL). In this study, we found that the hexane soluble fraction of the common fig Ficus carica (HF6-FC) is a potent inhibitor of osteoclastogenesis in RANKL-stimulated RAW264.7 cells and in bone marrow-derived macrophages (BMMs). HF6-FC exerts its inhibitory effects by suppression of p38 and NF-kappaB but activation of ERK. In addition, HF6-FC significantly decreased the expression of NFATc1 and c-Fos, the master regulator of osteoclast differentiation. The data indicate that components of HF6-FC may have therapeutic effects on bone-destructive processes such as osteoporosis, rheumatoid arthritis, and periodontal bone resorption.
Korean Journal of Physiology and Pharmacology 12/2009; 13(6):417-24. · 0.96 Impact Factor
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Jin-Hyuk Lee,
Yun-Hee Lee,
Hyo-Jung Lee,
Hyo-Jeong Lee,
Eun-Ok Lee,
Kwang Seok Ahn,
Bum Sang Shim,
Hyunsu Bae,
Seung-Hoon Choi,
Kyoo-Seok Ahn,
Nam-In Baek, Dae-Keun Kim,
Sung-Hoon Kim
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ABSTRACT: Solanum lyratum herba (SLH) has been traditionally used for the treatment of febrifuge, diarrhea, eye disease and cancer with little scientific evidences. Thus, in the present study, to elucidate the antitumor mechanism of SLH: in vitro and in vivo experiments were performed with hexane fraction of Solanum lyratum herba (HSLH).
Cytotoxicity assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, flow cytometric analysis for sub-G1 peaks, Western blot analysis were used with the antibodies of apoptosis related proteins in vitro. In addition, the effect of HSLH on in vivo tumor growth was evaluated in Lewis lung carcinoma (LLC) tumor model and immunohistochemistry also was performed with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in tumor section.
HSLH exhibited cytotoxicity against LLC cells most effectively among its solvent fractions. Ladder like DNA fragmentation and apoptotic features such as chromatin condensation and apoptotic bodies were observed in HSLH treated LLC cells by 4'-6-diamidino-2-phenylindole staining. HSLH also significantly increased sub-G(1) peaks, activated caspase-8, -9 and -3 proteins and cleaved poly(ADP-ribose) polymerase (PARP). Furthermore, HSLH increased the phosphorylation of extracellular signal-regulated kinase (ERK), transiently activated phospho-JNK (c-jun N-terminal kinase) and downregulated phospho-p38 MAPK. In addition, we have found for the first time HSLH treatment effectively suppressed the in vivo growth of LLC to up to approximately 30% of untreated control at 50mg/kg and significantly increased apoptotic expression in tumor section by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Taken together, these findings strongly demonstrate that hexane fraction of Solanum lyratum herba exerts antitumor activity via caspase activation and MAPK regulation and can be effectively applied to lung cancer as a cancer chemopreventive agent.
Journal of ethnopharmacology 06/2009; 123(1):121-7. · 2.32 Impact Factor
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Byoung-Mog Kwon,
Sung-Hoon Kim,
Nam-In Baek,
Sa Im Lee,
Eun Jeong Kim,
Jae Heon Yang,
Byeong Suk Chae,
Jae Hyeok Lee,
Hee Wook Park,
Jeong-Suk Park, Dae Keun Kim
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ABSTRACT: The methanolic extract of the roots of Polygonum multiflorum (Polygonaceae) was found to show inhibitory activity towards farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two anthraquinone glycosides, as inhibitors of FPTase. These compounds inhibited the FPTase activity in a dose-dependent manner.
Archives of Pharmacal Research 05/2009; 32(4):495-9. · 1.59 Impact Factor
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ABSTRACT: Icariside II (IS) isolated from the roots of Epimedium koreanum Nakai was known to have antioxidant activity and inhibit melanogenesis and hypoxia inducible factor. We report here for the first time that IS induces apoptosis through its anti-inflammatory effects in PC-3 prostate cancer cells. IS exerted cytotoxicity against PC-3 cells with IC(50) of approximately 20 microM. IS suppressed both constitutive and arachidonic acid (AA)-induced cyclooxygenase-2 (COX-2) expression as well as reduced prostaglandin E2 (PGE2) levels in PC-3 cells even at a low concentrations (5 and 10 microM). Additionally, IS increased sub G1 apoptotic portion and exhibited terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL)-positive apoptotic bodies in PC-3 cells at higher concentrations (20 and 40 microM). Furthermore, IS attenuated the mitochondrial membrane potential, released cytochrome C into cytosol, activated caspase-9, -8, and -3 expressions and cleaved poly (ADP-ribose) polymerase (PARP) in PC-3 cells. Consistently, COX-2, inducible NO synthase (iNOS), and vascular endothelial growth factor (VEGF) expressions were suppressed while in parallel inducing apoptosis in hormone-independent prostate carcinoma cells PC-3. Moreover, exogeneous PGE2 inhibited IS induced PARP cleavage in PC-3 cells and also knockdown of COX-2 by siRNA potentiated IS induced PARP cleavage, thereby implicating the critical role of COX-2 pathway in IS induced apoptosis. Taken together, these findings demonstrate that IS initiates the inhibition of COX-2/PGE(2) pathway and then induces apoptosis mainly via mitochondrial dependent pathway in PC-3 prostate cancer cells as a potent cancer chemotherapeutic agent.
Cancer letters 04/2009; 280(1):93-100. · 4.86 Impact Factor
