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ABSTRACT: Numerous studies have demonstrated that autophagy is associated with cancer development. Thus, agents to induce autophagy could be employed in some cases for the treatment of cancer. Our results showed that tetrandrine significantly decreased the viability of SAS cells in a concentration- and time-dependent manner. Tetrandrine induced nuclear condensation, demonstrated by DAPI staining. The early events in apoptosis analysed by Annexin V/PI staining indicated that the percentage of cells staining positive for Annexin V was slightly increased in SAS cells with tetrandrine treatment but was much lower following bafilomycin A1 pre-treatment. Tetrandrine caused AVO and MDC induction in SAS cells in a concentration-dependent manner by fluorescence microscopy. Tetrandrine also caused LC-3 expression in SAS cells in a time-dependent manner. Our results show that tetrandrine treatment induced the levels of cleaved caspase-3 in a concentration- and time-dependent manner. Tetrandrine treatment induced the levels of LC-3 II, Atg-5, beclin-1, p-S6, p-ULK, p-mTOR, p-Akt (S473) and raptor. Tetrandrine decreased cell viability, but bafilomycin A1, 3-MA, chloroquine and NAC protected tetrandrine-treated SAS cells against decrease of cell viability. Atg-5, beclin-1 siRNA decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells and protected tetrandrine-treated SAS cells against decrease in cell viability. Chloroquine, NAC and bafilomycin A1 also decreased tetrandrine-induced cleaved caspase-3 and cleaved PARP in SAS cells. Our results indicate the tetrandrine induces apoptosis and autophagy of SAS human cancer cells via caspase-dependent and LC3-I and LC3-II‑dependent pathways.
International Journal of Oncology 05/2013; · 2.40 Impact Factor
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ABSTRACT: Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β -catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/ β -catenin signaling of SP cells. The Wnt signaling transducers such as β -catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β -catenin degradation promoting kinase GSK-3 α / β was increased. Consistently, the protein levels of β -catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β -catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/ β -catenin signaling, and inhibition of EMT.
Evidence-based Complementary and Alternative Medicine 01/2013; 2013:146136. · 4.77 Impact Factor
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ABSTRACT: BACKGROUND: Hyperglycemia is an important risk factor for cardiovascular diseases no matter if it resulted from type I or type II diabetes mellitus. High glucose-induced generation of reactive oxygen species (ROS) can lead to diabetic cardiomyopathy. In our previous study, we showed that NADPH oxidase-related ROS-induced apoptosis is mediated via the JNK-dependent activation of NF-κB in cardiomyocytes exposed to high glucose (HG). OBJECTIVE: In this study, we investigated the mechanisms governing the anti-apoptotic effect of diallyl trisulfide (DATS) on HG-exposed cardiac cells both in vitro and in vivo. METHODS: H9c2 cells were incubated with media containing 5.5 or 33mM of glucose for 36h in the presence or absence of DATS. RESULTS: We found that DATS treatment led to a dose-dependent decrease in ROS levels as well as protein levels of p22phox, gp91phox, phosphorylated JNK, and phosphorylated c-Jun. In addition, DATS inhibited the HG-induced activation of caspase 3 as well as the nuclear translocation of NF-κB. Similar results were observed in HG-exposed neonatal primary cardiomyocytes and streptozotocin-treated diabetic rats. Echocardiographic data showed that DATS administration led to a marked increase in fractional shortening and cardiac output. CONCLUSION: DATS appears to suppress high glucose-induced cardiomyocyte apoptosis by inhibiting NADPH oxidase-related ROS and its downstream JNK/NF-κB signaling, and may possess the potential on the therapy of diabetic cardiomyopathy.
International journal of cardiology 11/2012; · 7.08 Impact Factor
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ABSTRACT: Leukemia, one of the causes of cancer-related death in humans, is an aggressive malignancy via the rapid growth of abnormal white blood cells. The aim of this study was to determine the anti-leukemia effect of glycyrrhizic acid (GA) on a mouse leukemia cell line, WEHI-3. GA, an active compound in Glycyrrhiza glabra, has been proven to induce cytotoxic effects in many cancer cell lines. In the current study, we investigated the effects of GA in mouse leukemia cells in vitro. The results indicated that GA induced morphological changes, G0/G1 phase arrest, apoptosis and DNA damage in WEHI-3 cells as determined by phase contrast microscopy, DAPI-staining, flow cytometry and comet assay. The results from the flow cytometric assay showed that GA increased ROS levels, reduced the mitochondrial membrane potential (ΔΨm) and stimulated caspase-3 activity in WEHI-3 cells. GA regulated the intrinsic and extrinsic apoptosis-associated protein expression which was determined by western blotting. In addition, endoplasmic reticulum (ER) stress responses were observed in GA-treated WEHI-3 cells. GA promoted the trafficking of apoptosis-inducing factor (AIF), cytochrome c and endonuclease G (Endo G) in WEHI-3 cells. Based on this evidence, GA-triggered apoptosis occurs through the death receptor, mitochondria-mediated and ER stress multiple signaling pathways.
Oncology Reports 09/2012; 28(6):2069-76. · 1.84 Impact Factor
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ABSTRACT: Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in
men. However, it is unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility
in human colon cancer cells. Upregulation of cyclooxygenase-2 (COX-2) is reported to associate with the development of cancer
cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002 (Akt activation
inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), or QNZ (NFκB inhibitor),
we found that PGE2 treatment increases COX-2 via Akt and ERK1/2 pathways, thus promoting cellular motility in human LoVo cancer
cells. We further observed that 17β-estradiol treatment inhibits PGE2-induced COX-2 expression and cellular motility via suppressing
activation of Akt and ERK1/2 in human LoVo cancer cells. Collectively, these results suggest that 17β-estradiol treatment
dramatically inhibits PGE2-induced progression of human LoVo colon cancer cells.
KeywordsEstrogen-Prostaglandin E2-Human colon cancer cell-COX-2-Cell motility
Molecular and Cellular Biochemistry 04/2012; 342(1):63-70. · 2.06 Impact Factor
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ABSTRACT: It has been shown that deguelin, one of the compounds of rotenoids from flavonoid family, induced cytotoxic effects through induction of cell cycle arrest and apoptosis in many types of human cancer cell lines, but deguelin-affected DNA damage and repair gene expression (mRNA) are not clarified yet. We investigated the effects of deguelin on DNA damage and associated gene expression in human lung cancer NCI-H460 cells in vitro. DNA damage was assayed by using the comet assay and DNA gel electrophoresis and the results indicated that NCI-H460 cells treated with 0, 50, 250 and 500 nM deguelin led to a longer DNA migration smear based on the single cell electrophoresis and DNA fragmentation occurred based on the examination of DNA gel electrophoresis. DNA damage and repair gene expression (mRNA) were evaluated by using real-time PCR assay and the results indicated that 50 and 250 nM deguelin for a 24-h exposure in NCI-H460 cells, decreased the gene levels of breast cancer 1, early onset (BRCA1), DNA-dependent serine/threonine protein kinase (DNA-PK), O6-methylguanine-DNA methyltransferase (MGMT), p53, ataxia telangiectasia mutated (ATM) and ataxia-telangiectasia and Rad3-related (ATR) mRNA expressions. Collectively, the present study showed that deguelin caused DNA damage and inhibited DNA damage and repair gene expressions, which might be due to deguelin-inhibited cell growth in vitro.
Oncology Reports 04/2012; 27(4):959-64. · 1.84 Impact Factor
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ABSTRACT: There are increasing pieces of evidence suggesting that the recurrence of cancer may result from a small subpopulation of cancer stem cells, which are resistant to the conventional chemotherapy and radiotherapy. We investigated the effects of Chinese herbal mixture Tien-Hsien Liquid (THL) on the cancer stem-like side population (SP) cells isolated from human hepatoma cells. After sorting and subsequent culture, the SP cells from Huh7 hepatoma cells appear to have higher clonogenicity and mRNA expressions of stemness genes such as SMO, ABCG2, CD133, β-catenin, and Oct-4 than those of non-SP cells. At dose of 2 mg/mL, THL reduced the proportion of SP cells in HepG2, Hep3B, and Huh7 cells from 1.33% to 0.49%, 1.55% to 0.43%, and 1.69% to 0.27%, respectively. The viability and colony formation of Huh7 SP cells were effectively suppressed by THL dose-dependently, accompanied with the inhibition of stemness genes, e.g., ABCG2, CD133, and SMO. The tumorigenicity of THL-treated Huh7 SP cells in NOD/SCID mice was also diminished. Moreover, combination with THL could synergize the effect of doxorubicin against Huh7 SP cells. Our data indicate that THL may act as a cancer stem cell targeting therapeutics and be regarded as complementary and integrative medicine in the treatment of hepatoma.
Evidence-based Complementary and Alternative Medicine 01/2012; 2012:617085. · 4.77 Impact Factor
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ABSTRACT: To focus on bee venom-induced apoptosis in human bladder cancer TSGH-8301 cells and to investigate its signaling pathway to ascertain whether intracellular calcium iron (Ca(2+)) is involved in this effect.
Bee venom-induced cytotoxic effects, productions of reactive oxygen species and Ca(2+) and the level of mitochondrial membrane potential (ΔΨm) were analyzed by flow cytometry. Apoptosis-associated proteins were examined by Western blot analysis and confocal laser microscopy.
Bee venom-induced cell morphological changes and decreased cell viability through the induction of apoptosis in TSGH-8301 cell were found. Bee venom promoted the protein levels of Bax, caspase-9, caspase-3 and endonuclease G. The enhancements of endoplasmic reticulum stress-related protein levels were shown in bee venom-provoked apoptosis of TSGH-8301 cells. Bee venom promoted the activities of caspase-3, caspase-8, and caspase-9, increased Ca(2+) release and decreased the level of ΔΨm. Co-localization of immunofluorescence analysis showed the releases of endonuclease G and apoptosis-inducing factor trafficking to nuclei for bee venom-mediated apoptosis. The images revealed evidence of nuclear condensation and formation of apoptotic bodies by 4',6-diamidino-2-phenylindole staining and DNA gel electrophoresis showed the DNA fragmentation in TSGH-8301 cells.
Bee venom treatment induces both caspase-dependent and caspase-independent apoptotic death through intracellular Ca(2+) -modulated intrinsic death pathway in TSGH-8301 cells.
International Journal of Urology 12/2011; 19(1):61-70. · 1.75 Impact Factor
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Ru-Duan Yeh,
Jung-Chou Chen, Tung-Yuan Lai,
Jai-Sing Yang,
Chun-Shu Yu,
Jo-Hua Chiang,
Chi-Cheng Lu,
Su-Tso Yang,
Chien-Chih Yu,
Shu-Jen Chang,
Hui-Yi Lin,
Jing-Gung Chung
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ABSTRACT: Gallic acid (GA) induces apoptosis in different types of cancer cell lines. In this study, we investigate the apoptotic effects induced by GA in human promyelocytic leukemia HL-60 cells, and clarify the underlying mechanism. Our results showed that GA reduced the viability of HL-60 cells in a dose- and time-dependent manner. GA led to G(0)/G(1) phase arrest in HL-60 cells through promoting p21 and p27 and inhibiting the levels of cyclin D and cyclin E. GA caused DNA damage and fragmentation in HL-60 cells as assayed using DAPI staining and Comet assay. Flow cytometric analysis revealed that GA increased Ca(2+) levels and reduced the mitochondrial membrane potential (ΔΨ(m)) in HL-60 cells. Apoptotic protein expressions were determined by Western blotting. The results indicated that GA-mediated apoptosis of HL-60 cells mainly depended on mitochondrial pathway, by promoting the release of cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (Endo G) and by up-regulating the protein expression of Bcl-2-associated X protein (BAX), caspase-4, caspase-9 and caspase-3. In addition, GA also activated the death receptor-dependent pathway by enhancing the protein expressions of fatty acid synthase (FAS), FAS ligand (FASL), caspase-8 and BCL-2 interacting domain (BID). We determined the mRNA expression of the gene levels of these proteins by real-time PCR. The results showed that GA-mediated apoptosis of HL-60 cells mainly depended on up-regulation of the mRNA of caspase-8, caspase-9, caspase-3, AIF and Endo G. In conclusion, GA-induced apoptosis occurs through the death receptor and mitochondria-mediated pathways. The evaluation of GA as a potential therapeutic agent for treatment of leukemia seems warranted.
Anticancer research 09/2011; 31(9):2821-32. · 1.73 Impact Factor
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ABSTRACT: Currently, there are no diagnostic or metastatic markers that can be used in early diagnosis and treatment of human hepatocellular carcinoma (HCC). The aim of this study was to find a molecular marker that regulated migration and metastasis in HCC. We analyzed the gene expression of β-catenin, c-Myc and IL-8 in human HCC tissue by RT-PCR and immunohistochemistry and analyzed five variously differentiated HCC cell lines by Western blotting and migration and invasion assays to find markers for HCC diagnosis and HCC metastasis. mRNA expression of β-catenin was significantly higher in the tumor area compared to the non-tumor area and was more abundant in specimens of late-stage HCC. Immunohistochemistry revealed that the translocation of β-catenin into the nucleus was closely correlated with IL-8 protein levels and tumor stage. Similarly, the level of expression and nuclear translocation of β-catenin was greater in HA22T cells with high proliferative activity than in HCC cell lines with low proliferative activity (PLC, Hep3B, HepG2). Knockdown of the β-catenin gene with β-catenin antisense oligonucleotides resulted in inhibition of cell migration and invasion of HA22T cells. Taken together, these results suggest that β-catenin may be a suitable diagnostic marker of metastasis in human HCC.
Oncology Reports 08/2011; 26(2):415-22. · 1.84 Impact Factor
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ABSTRACT: Melanoma is one of the most common cancers worldwide and its incidence has been increasing over the past few decades. Gallic acid (GA) can inhibit the growth of human cancer cells in vitro and in vivo. However, there is no available information to address the effects of GA on migration and invasion of human skin cancer cells. Matrix metalloproteinases (MMPs), zinc-dependent proteolytic enzymes, play an important role in the invasion, metastasis, and angiogenesis of cancer cells. Therefore, MMPs are one of the targets for agents to suppress and that could inhibit the migration and invasion of cancer cells. GA affected the viable A375.S2 cells by propidium iodide exclusion and flow cytometric analysis. Cell migration and invasion were investigated by Boyden chamber assay and we also determined the levels of protein and mRNA expression cell migration and invasion by gelatin zymography, western blotting, and real-time PCR assays. In this study, we examined the influence of GA on the protein levels and gene expression of MMP-2 and MMP-9 and in-vitro migration and invasiveness of human melanoma cells. GA decreases the MMPs and associated signal pathway protein and MMPs mRNA levels in A375.S2 human melanoma cells. Our findings suggest that GA has antimetastatic potential by decreasing invasiveness of cancer cells. Moreover, this action of GA was involved in the Ras, p-ERK signaling pathways resulting in inhibition of MMP-2 in A375.S2 human melanoma cells. These data, therefore, provide evidence for the role of GA as a potential cancer chemotherapeutic agent, which can markedly inhibit the invasive capacity of melanoma cells.
Melanoma research 08/2011; 21(4):267-73. · 2.06 Impact Factor
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Kung-Wen Lu,
Jung-Chou Chen, Tung-Yuan Lai,
Jai-Sing Yang,
Shu-Wen Weng,
Yi-Shih Ma,
Hui-Yi Lin,
Rick Sai-Chuan Wu,
King-Chuen Wu,
W Gibson Wood,
Jing-Gung Chung
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ABSTRACT: Gypenosides (Gyp) are the major components of Gynostemma pentaphyllum Makino. The authors investigated the effects of Gyp on cell morphology, viability, cell cycle distribution, and induction of apoptosis in human oral cancer SAS cells and the determination of murine SAS xenograft model in vivo.
Flow cytometry was used to quantify the percentage of viable cells; cell cycle distribution; sub-G1 phase (apoptosis); caspase-3, -8, and -9 activity; reactive oxygen species (ROS) production, intracellular Ca(2+) determination; and the level of mitochondrial membrane potential (ΔΨ(m)). Western blotting was used to examine levels of apoptosis-associated proteins, and confocal laser microscopy was used to examine the translocation of proteins in cells.
Gyp induced morphological changes, decreased the percentage of viable cells, caused G0/G1 phase arrest, and triggered apoptotic cell death in SAS cells. Cell cycle arrest induced by Gyp was associated with apoptosis. The production of ROS, increased intracellular Ca(2+) levels, and the depolarization of ΔΨ(m) were observed. Gyp increased levels of the proapoptotic protein Bax but inhibited the levels of the antiapoptotic proteins Bcl-2 and Bcl-xl. Gyp also stimulated the release of cytochrome c and Endo G. Translocation of GADD153 to the nucleus was stimulated by Gyp. Gyp in vivo attenuated the size and volume of solid tumors in a murine xenograft model of oral cancer.
Gyp-induced cell death occurs through caspase-dependent and caspase-independent apoptotic signaling pathways, and the compound reduced tumor size in a xenograft nu/nu mouse model of oral cancer.
Integrative Cancer Therapies 06/2011; 11(2):129-40. · 2.14 Impact Factor
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ABSTRACT: Hyperglycemia-induced generation of reactive oxygen species (ROS) can lead to cardiomyocyte apoptosis and cardiac dysfunction. However, the mechanism by which high glucose causes cardiomyocyte apoptosis is not clear. In this study, we investigated the signaling pathways involved in NADPH oxidase-derived ROS-induced apoptosis in cardiomyocytes under hyperglycemic conditions. H9c2 cells were treated with 5.5 or 33 mM glucose for 36 h. We found that 33 mM glucose resulted in a time-dependent increase in ROS generation as well as a time-dependent increase in protein expression of p22(phox), p47(phox), gp91(phox), phosphorylated IκB, c-Jun N-terminal kinase (JNK) and p38, as well as the nuclear translocation of NF-kB. Treatment with apocynin or diphenylene iodonium (DPI), NADPH oxidase inhibitors, resulted in reduced expression of p22(phox), p47(phox), gp91(phox), phosphorylated IκB, c-Jun N-terminal kinase (JNK) and p38. In addition, treatment with JNK and NF-kB siRNAs blocked the activity of caspase-3. Furthermore, treatment with JNK, but not p38, siRNA inhibited the glucose-induced activation of NF-κB. Similar results were obtained in neonatal cardiomyocytes exposed to high glucose concentrations. Therefore, we propose that NADPH oxidase-derived ROS-induced apoptosis is mediated via the JNK-dependent activation of NF-κB in cardiomyocytes exposed to high glucose.
Journal of Cellular Physiology 05/2011; 227(4):1347-57. · 3.87 Impact Factor
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Jen-Jyh Lin,
Hui-Ying Hsu,
Jai-Sing Yang,
Kung-Wen Lu,
Rick Sai-Chuen Wu,
King-Chuen Wu, Tung-Yuan Lai,
Po-Yuan Chen,
Chia-Yu Ma,
W Gibson Wood,
Jing-Gung Chung
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ABSTRACT: We have shown that gypenosides (Gyp) induced cell cycle arrest and apoptosis in many human cancer cell lines. However, there are no reports showing that show Gyp acts on human leukemia HL-60 cells in vitro and in a murine xenograft model in vivo. In the present study effects of Gyp on cell morphological changes and viability, cell cycle arrest and induction of apoptosis in vitro and effects on Gyp in an in vivo murine xenograft model. Results indicated that Gyp induced morphological changes, decreased cell viability, induced G0/G1 arrest, DNA fragmentation and apoptosis (sub-G1 phase) in HL-60 cells. Gyp increased reactive oxygen species production and Ca(2+) levels but reduced mitochondrial membrane potential in a dose- and time-dependent manner. Gyp also changed one of the primary indicators of endoplasmic reticulum (ER) stress due to the promotion of ATF6-α and ATF4-α associated with Ca(2+) release. Gyp reduced the ratio of Bcl-2 to Bax due to an increase in the pro-apoptotic protein Bax and inhibited levels of the anti-apoptotic protein Bcl-2. Oral consumption of Gyp reduced tumor size of HL-60 cell xenograft mode mice in vivo. These results provide new information on understanding mechanisms by which Gyp induces cell cycle arrest and apoptosis in vitro and in vivo.
Phytomedicine: international journal of phytotherapy and phytopharmacology 05/2011; 18(12):1075-85. · 2.17 Impact Factor
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Kung-Wen Lu,
Jung-Chou Chen, Tung-Yuan Lai,
Jai-Sing Yang,
Shu-Wen Weng,
Yi-Shih Ma,
Pei-Jung Lu,
Jing-Ru Weng,
Fu-Shin Chueh,
W Gibson Wood,
Jing-Gung Chung
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ABSTRACT: Gypenosides (Gyp), found in Gynostemma pentaphyllum Makino, has been used as a folk medicine in the Chinese population for centuries and is known to have diverse pharmacologic effects, including anti-proliferative and anti-cancer actions. However, the effects of Gyp on prevention from invasion and migration of oral cancer cells are still unsatisfactory. The purpose of this study was to investigate effects of Gyp treatment on migration and invasion of SAS human oral cancer cells. SAS cells were cultured in the presence of 90 and 180 μg/mL Gyp for 24 and 48 hours. Gyp induced cytotoxic effects and inhibited SAS cells migration and invasion in dose- and time-dependent response. Wound-healing assay and boyden chamber assay were carried out to investigate Gyp-inhibited migration and invasion of SAS cells. Gyp decreased the abundance of several proteins, including nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), extracellular signal-regulated kinase 1/2 (ERK1/ 2), matrix metalloproteinase-9, -2 (MMP-9, -2), sevenless homolog (SOS), Ras, urokinase-type plasminogen activator (uPA), focal adhesion kinase (FAK) and RAC-alpha serine/threonine-protein kinase (Akt), in a time-dependent manner. In addition, Gyp decreased mRNA levels of MMP-2, MMP-7, MMP-9 but did not affect FAK and Rho A mRNA levels in SAS cells. These results provide evidences for the role of Gyp as a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of oral cancer cells. The inhibition of NF-κB and MMP-2, -7 and -9 signaling may be one of the mechanisms that is present in Gyp-inhibited cancer cell invasion and migration.
Human & Experimental Toxicology 05/2011; 30(5):406-15. · 1.31 Impact Factor
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ABSTRACT: Invasion of distant tissues by tumor cells is the primary cause of therapeutic failure in the treatment of malignant lung cancer cells. Receptor activator of nuclear factor-κB ligand (RANKL) and its receptor, RANK, play a key role in osteoclastogenesis and tumor metastasis. Intercellular adhesion molecule-1 (ICAM-1, also called CD54), a member of the immunoglobulin supergene family, is an inducible surface glycoprotein that mediates adhesion-dependent cell-to-cell interactions. The effects of RANKL on cell migration and ICAM-1 expression in human lung cancer cells are largely unknown. We found that RANKL directed the migration and increased ICAM-1 expression in human lung cancer (A549) cells. Pretreatment of A549 cells with the MAPK kinase (MEK) inhibitor PD98059 or U0126 inhibited RANKL-mediated migration and ICAM-1 expression. Stimulation of cells with RANKL increased the phosphorylation of MEK and extracellular signal-regulating kinase (ERK). In addition, an NF-κB inhibitor (PDTC) and IκB protease inhibitor (TPCK) also inhibited RANKL-mediated cell migration and ICAM-1 up-regulation. Taken together, these results suggest that the RANKL and RANK interaction acts through MEK/ERK, which in turn activates NF-κB, resulting in the activation of ICAM-1 and contributing to the migration of human lung cancer cells.
Journal of Cellular Biochemistry 03/2011; 112(3):933-41. · 2.87 Impact Factor
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Yuan-Chang Chang, Tung-Yuan Lai,
Chun-Shu Yu,
Hung-Yi Chen,
Jai-Sing Yang,
Fu-Shin Chueh,
Chi-Cheng Lu,
Jo-Hua Chiang,
Wen-Wen Huang,
Chia-Yu Ma,
Jing-Gung Chung
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ABSTRACT: Emodin is one of major compounds in rhubarb (Rheum palmatum L.), a plant used as herbal medicine in Chinese population. Although many reports have shown that emodin exhibits anticancer activity in many tumor cell types, there is no available information addressing emodin-affected apoptotic responses in the murine leukemia cell line (WEHI-3) and modulation of the immune response in leukemia mice. We investigated that emodin induced cytotoxic effects in vitro and affected WEHI-3 cells in vivo. This study showed that emodin decreased viability and induced DNA fragmentation in WEHI-3 cells. Cells after exposure to emodin for 24 h have shown chromatin condensation and DNA damage. Emodin stimulated the productions of ROS and Ca(2+) and reduced the level of ΔΨ(m) by flow cytometry. Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. In in vivo study, emodin enhanced the levels of B cells and monocytes, and it also reduced the weights of liver and spleen compared with leukemia mice. Emodin promoted phagocytic activity by monocytes and macrophages in comparison to the leukemia mice group. In conclusions, emodin induced apoptotic death in murine leukemia WEHI-3 cells and enhanced phagocytosis in the leukemia animal model.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011:523596. · 4.77 Impact Factor
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ABSTRACT: Dilong, also known as earthworm, has been widely used in traditional Chinese medicine (TCM) for thousands of years. Schwann cell migration and proliferation are critical for the regeneration of injured nerves and Schwann cells provide an essentially supportive role for neuron regeneration. However, the molecular mechanisms of migration and proliferation induced by dilongs in Schwann cells remain unclear. Here, we discuss the molecular mechanisms that includes (i) migration signaling, MAPKs (mitogen-activated protein kinases), mediated PAs and MMP2/9 pathway; (ii) survival and proliferative signaling, IGF-I (insulin-like growth factor-I)-mediated PI3K/Akt pathways and (iii) cell cycle regulation. Dilong stimulate RSC96 cell proliferation and migration. It can induce phosphorylation of ERK1/2 and p38, but not JNK, and activate the downstream signaling expression of PAs (plasminogen activators) and MMPs (matrix metalloproteinases) in a time-dependent manner. In addition, Dilong stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with chemical inhibitors (U0126 and SB203580), and small interfering ERK1/2 and p38 RNA, resulting in migration and uPA-related signal pathway inhibition. Dilong also induces the phosphorylation of IGF-I-mediated PI3K/Akt pathway, activates protein expression of PCNA (proliferating cell nuclear antigen) and cell cycle regulatory proteins (cyclin D1, cyclin E and cyclin A) in a time-dependent manner. In addition, it accelerates G(1)-phase progression with earlier S-phase entry and significant numbers of cells entered the S-phase. The siRNA-mediated knockdown of PI3K that significantly reduces PI3K protein expression levels, resulting in Bcl(2) survival factor reduction, revealing a marked blockage of G(1) to S transition in proliferating cells. These results reveal the unknown RSC96 cell migration and proliferation mechanism induced by dilong, which find use as a new medicine for nerve regeneration.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011:380809. · 4.77 Impact Factor
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ABSTRACT: CHM-1 [2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one] is a quinolone derivative that has been reported to induce apoptosis and inhibit invasion of cancer cells. However, there is no available information to address the effects of CHM-1 on leukemia cells in vivo. Therefore, the present study examined the effects of CHM-1 using a mouse model of leukemia. We established leukemia in mice by injecting WEHI-3 cells into BALB/c mice. Mice were then treated with or without CHM-1 (5 and 10 mg/kg). CHM-1 promoted the total survival rate of leukemic mice and these effects were dose-dependent. CHM-1 increased body weight and decreased spleen weight, but did not affect liver weight. The levels of cell markers Mac-3 and CD11b were reduced by CHM-1, indicating that the differentiation of macrophage precursor cells was inhibited. Levels of CD3 and CD19 were induced by CHM-1, suggesting that the differentiation of precursors of T and B cells was promoted in PBMC. Results of the present study indicate that CHM-1 has an inhibitory effect on leukemia induced in mice in vivo and warrants further study as to the mechanisms and effects in other types of cancer.
Leukemia & lymphoma 11/2010; 51(11):2098-102. · 2.40 Impact Factor
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Kuang-Chi Lai,
Shu-Chun Hsu,
Jai-Sing Yang,
Chao-Lin Kuo,
Siu-Wan Ip, Tung-Yuan Lai,
Shuw-Yuan Lin,
Ching-Che Huang,
Sheng-Chu Kuo,
W Gibson Wood,
Jing-Gung Chung
[show abstract]
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ABSTRACT: Matrix metalloproteinases (MMPs) play an important role in the invasion, metastasis and angiogenesis of cancer cells. Many agents have been shown to inhibit the cancer cell migration and invasion by suppression of MMPs. 2-(3-Methoxyphenyl)-6,7-methylenedioxoquinolin-4-one (MMEQ) is a derivative compound synthesized from quinolin and the purpose of this study is to determine whether or not cell migration would be reduced in human bladder cancer TSGH8301 cells after MMEQ treatment. Wound healing assay and boyden chamber assay were used in cell migration and invasion determinations. Cell migration and invasion inhibited by MMEQ exerted an inhibitory effect on the sevenless homolog-1 (SOS-1), protein kinase c (PKC), extracellular signal-regulated kinase (ERK) and Rho A for causing the inhibitions of MMP-2 and -9, and then followed by the inhibitions of invasion and migration. MMEQ also affected FAK, PI3K or inhibited growth factor receptor-bound protein 2 (GRB2), nuclear factor kappaB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) for cell proliferation inhibition. Therefore, MMEQ may serve as a drug in the prevention of tumor metastasis of bladder cancer in the future.
Human & Experimental Toxicology 10/2010; 30(8):1045-52. · 1.31 Impact Factor
