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ABSTRACT: Metastasis is a major cause of death of patients with malignant tumors. Matrix metalloproteinases (MMPs) are important for the migration and invasion of various types of cancer cell. Propofol is a known anesthetic agent, widely used for short-term anesthesia and for longer-term sedation. Propofol inhibits the proliferation of a variety of tumor cells, but there is no available information regarding propofol-inhibited migration and invasion of tumor cells in vitro. In this study, we investigated the effects of propofol on the migration and invasion of human lung carcinoma A549 cells. Wound healing assay and Boyden chamber assays indicated that propofol inhibited the migration and invasion of A549 cells in vitro. Gelatin zymographic analysis showed the inhibitory effect of propofol on the activation of expression MMP-2. Western blot analysis also indicated that propofol suppressed the protein expiration of growth factor receptor-bound protein 2 (GRB2), Jun N-terminal kinases 1/2 (p-JNK1/2), p-p38, MMP-2 and MMP-9 in A549 cells. Results from real-time PCR assay also showed that propofol inhibited the mRNA gene expression of MMP-2, -7 and -9, and enhanced that of tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 in A549 cells. Taken together, these data show that propofol inhibits MMP-2 and -9 mRNA and protein expressions, resulting in suppression of lung cancer cell invasion and migration in vitro.
Anticancer research 11/2012; 32(11):4833-42. · 1.73 Impact Factor
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Kuo-Ching Liu,
Chun-Yi Yen, Rick Sai-Chuen Wu,
Jai-Sing Yang,
Hsu-Feng Lu,
Kung-Wen Lu,
Chyi Lo,
Hung-Yi Chen,
Nou-Ying Tang,
Chih-Chung Wu,
Jing-Gung Chung
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ABSTRACT: Prostate cancer has its highest incidence and is becoming a major concern. Many studies have shown that traditional Chinese medicine exhibited antitumor responses. Quercetin, a natural polyphenolic compound, has been shown to induce apoptosis in many human cancer cell lines. Although numerous evidences show multiple possible signaling pathways of quercetin in apoptosis, there is no report to address the role of endoplasmic reticulum (ER) stress in quercetin-induced apoptosis in PC-3 cells. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human prostate cancer PC-3 cells. Cells were treated with quercetin for 24 and 48 h and at various doses (50-200 μM), and cell morphology and viability decreased significantly in dose-dependent manners. Flow cytometric assay indicated that quercetin at 150 μM caused G0/G1 phase arrest (31.4-49.7%) and sub-G1 phase cells (19.77%) for 36 h treatment and this effect is a time-dependent manner. Western blotting analysis indicated that quercetin induces the G0/G1 phase arrest via decreasing the levels of CDK2, cyclins E, and D proteins. Quercetin also stimulated the protein expression of ATF, GRP78, and GADD153 which is a hall marker of ER stress. Furthermore, PC-3 cells after incubation with quercetin for 48 h showed an apoptotic cell death and DNA damage which are confirmed by DAPI and Comet assays, leading to decrease the antiapoptotic Bcl-2 protein and level of ΔΨ(m) , and increase the proapoptotic Bax protein and the activations of caspase-3, -8, and -9. Moreover, quercetin promoted the trafficking of AIF protein released from mitochondria to nuclei. These data suggest that quercetin may induce apoptosis by direct activation of caspase cascade through mitochondrial pathway and ER stress in PC-3 cells. © 2012 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Environmental Toxicology 03/2012; · 2.41 Impact Factor
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Jaung-Geng Lin,
Ming-Jen Fan,
Nou-Ying Tang,
Jai-Sing Yang,
Te-Chun Hsia,
Jen-Jyh Lin,
Kuang-Chi Lai, Rick Sai-Chuen Wu,
Chia-Yu Ma,
W Gibson Wood,
Jing-Gung Chung
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ABSTRACT: The edible mushroom (fungus) Agaricus blazei Murill (ABM) is a health food in many countries. Importantly, it has been shown to have antitumor and immune effects. There is no available information on ABM-affected immune responses in leukemia mice in vivo. Experimental Design. In this study, the authors investigated the immunopotentiating activities of boiled water-soluble extracts from desiccated ABM in WEHI-3 leukemia mice. The major characteristic of WEHI-3 leukemia mice are enlarged spleens and livers after intraperitoneal injection with murine leukemia WEHI-3 cells. Isolated T cells from spleens of ABM-treated mice resulted in increased T-cell proliferation compared with the untreated control with concanavalin A stimulation.
ABM decreased the spleen and liver weights when compared with WEHI-3 leukemia mice and this effect was a dose-dependent response. ABM promoted natural killer cell activity and phagocytosis by macrophage/monocytes in leukemia mice in a dose-dependent manner. ABM also enhanced cytokines such as interleukin (IL)-1β, IL-6, and interferon-γ levels but reduced the level of IL-4 in WEHI-3 leukemia mice. Moreover, ABM increased the levels of CD3 and CD19 but decreased the levels of Mac-3 and CD11b in leukemia mice.
The ABM extract is likely to stimulate immunocytes and regulate immune response in leukemia mice in vivo.
Integrative Cancer Therapies 03/2012; 11(1):29-36. · 2.14 Impact Factor
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ABSTRACT: Propofol (2,6-diisopropylphenol) is the most extensively used general anesthetic-sedative agent and it is employed in clinical patients. It has been shown that propofol exhibits anticancer activities. However, there is no available information to address propofol-induced cytotoxic effects and affected gene expressions on murine leukemia cells. Therefore, we investigated the effects of propofol on the levels of protein and gene expression, which are associated with apoptotic death in mouse leukemia RAW 264.7 cells in vitro. Results indicated that propofol induced cell morphological changes, cytotoxicity, and induction of apoptosis in RAW 264.7 cells in vitro. Western blot analysis demonstrated that propofol promoted Fas, cytochrome c, caspase-9 and -3 active form and Bax levels, but inhibited Bcl-xl protein level which led to cell apoptosis. Furthermore, cDNA microarray assay indicated that propofol significantly enhanced 5 gene expressions (Gm4884; Gm10883; Lce1c; Lrg1; and LOC100045878) and significantly suppressed 26 gene expressions (Gm10679; Zfp617; LOC621831; LOC621831; Gm5929; Snord116; Gm3994; LOC380994; Gm5592; LOC380994; Gm4638; LOC280487; Gm4638; Tex24; A530064D06Rik; BC094916; EG668725; Gm189; Hist2h3c2; Gm8020; Snord115; Gm3079; Olfr198; Tdh; Snord115; and Olfr1249). Based on these observations, propofol-altered apoptosis-related proteins might result from induction of apoptotic gene expression and inhibition of cell growth gene expression, which finally led to apoptosis in a mouse leukemia cell line (RAW 264.7) in vitro. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011.
Environmental Toxicology 07/2011; · 2.41 Impact Factor
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ABSTRACT: Etomidate is an important tool in the arsenal of the emergency physician, and it has been used in a variety of scenarios for both intubation and procedural sedation. In the present study, we investigated the cytotoxicity of etomidate including induction of apoptosis, and levels of protein and gene expressions associated with apoptotic cell death in murine leukemia RAW264.7 cells in vitro. Cytotoxic and apoptotic responses to etomidate of RAW264.7 cells, including cell morphological changes and cell viability were examined and measured by phase-contrast microscopy and flow cytometric assay, respectively. Results indicated that etomidate increased apoptotic cell morphological changes and reduced cell viability in RAW264.7 cells. 4',6-Diamidino-2-phenylindole (DAPI) staining also showed that etomidate induced the formation of apoptotic bodies, a characteristic of apoptosis. Results from Western blotting indicated that etomidate enhanced the levels of cytochrome c, apoptosis-inducing factor (AIF), endonuclease G (Endo G), caspase-9, caspase-3 active form and Bax proteins, but it inhibited the expression of Bcl-xl, leading to apoptosis. DNA microarray assay indicated that etomidate increased the expression of 17 genes (LOC676175; Gm14636; 2810021G02Rik; Iltifb; Olfr1167; Ttc30b; Olfr766; Gas5; Rgs1; LOC280487; V1rd4; Hist1h2bc; V1rj3; Gm10366; Olfr192; Gm10002 and Cspp1) and reduced the expression of 15 genes: (Gm10152; Gm5334; Olfr216; Lcn9; Gm10683; Gm5100; Tdgf1; Cypt2; Gm5595; 1700018F24Rik; Gm10417; Maml2; Olfr591; Trdn and Apol7c). In conclusion, etomidate induced cytotoxic and apoptotic effects the in murine leukemia RAW264.7 cells in vitro.
Anticancer research 06/2011; 31(6):2203-8. · 1.73 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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Ping-Ping Wu,
Hui-Wen Chung,
Kuo-Ching Liu, Rick Sai-Chuen Wu,
Jai-Sing Yang,
Nou-Ying Tang,
Chyi Lo,
Te-Chun Hsia,
Chien-Chih Yu,
Fu-Shin Chueh,
Song-Shei Lin,
Jing-Gung Chung
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ABSTRACT: Diallyl sulfide (DAS), one of the main active constituents of garlic, causes growth inhibition of cancer cells in vitro and promotes immune responses in vivo in experimental settings. However, its effects on the induction of cell cycle and apoptosis in human cervical cancer cells are still unclear. The aims of this study were to explore the anti-cancer effects of DAS in HeLa human cervical cancer cells and to investigate the underlying mechanisms in vitro. Cytotoxicity and apoptosis in HeLa human cervical cancer cells were examined by the morphological changes, viability assay, 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining, comet assay, Western blotting and confocal microscopy examination. The results showed that DAS treatment for 24-72 h resulted in a marked decrease in cell viability time- and dose-dependently. Flow cytometric analysis showed that a 48-h treatment of 75 µM DAS induced G0/G1 cell cycle arrest and sub-G1 phase (apoptosis) in HeLa cells. Typical apoptotic nucleus alterations were observed by fluorescence microscopy in HeLa cells after exposure to DAS using DAPI staining. Cells treated with different concentrations of DAS also showed changes typical of apoptosis such as morphological changes, DNA damage and fragmentation, dysfunction of mitochondria, cytochrome c release and increased expression of pro-caspase-3 and -9. DAS also promoted the release of AIF and Endo G from mitochondria in HeLa cells. In conclusion, DAS induced G0/G1 cell cycle arrest and apoptosis in HeLa cells through caspase- and mitochondria and p53 pathways providing further understanding of the molecular mechanisms of DAS action in cervical cancer. This study, therefore, revealed that DAS significantly inhibits the growth and induces apoptosis of human cervical cancer HeLa cells in vitro.
International Journal of Oncology 03/2011; 38(6):1605-13. · 2.40 Impact Factor
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ABSTRACT: Sleep deprivation (SD) leads to decreases in circulating levels of testosterone with unknown mechanisms. We tested the hypothesis that decreased testosterone levels associated with SD may be caused by serotonin-mediated inhibition of its production. Male rats were subjected to SD for 24 or 48 h using the dish-over-water-method with a Rechtschaffen apparatus. Serum testosterone, corticosterone and serotonin (5-HT) concentrations were assessed thereafter, as were testicular StAR and 5-HT 2 receptor levels. SD, regardless of duration led to significant decreases in serum testosterone levels and testicular steroid acute regulatory protein (StAR) protein expression, while 5-HT levels were significantly elevated (all P<0.05). Corticosterone concentrations were significantly increased in 48 h SD rats (P<0.05). In primary Leydig cell cultures, 5-HT decreased chorionic gonadotropin-induced testosterone secretion and StAR expression, which appeared to be dependent on 5-HT 2 receptor activation but independent of cyclic AMP signaling. These findings suggest that decreased serum testosterone levels in SD rats may be the result of 5-HT-related inhibition of testosterone production and decreased testicular expression of StAR protein.
Neuroscience Letters 03/2011; 494(2):124-9. · 2.11 Impact Factor
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Jing-Pin Lin,
Jai-Sing Yang,
Jen-Jyh Lin,
Kuang-Chi Lai,
Hsu-Feng Lu,
Chia-Yu Ma, Rick Sai-Chuen Wu,
King-Chuan Wu,
Fu-Shin Chueh,
W Gibson Wood,
Jing-Gung Chung
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ABSTRACT: Numerous studies have shown that rutin has anticancer effects. We have previously reported that rutin induced cell cycle arrest and apoptosis in murine leukemia WEHI-3 cells in vitro and in vivo. However, there are no data showing that rutin inhibits human leukemia HL-60 cells in vivo in a murine xenograft animal model. Human leukemia HL-60 cells were implanted into mice and treated with vehicle (1% DMSO), rutin (120 mg/kg of body weight) or vinblastine (120 μg/kg of body weight). Compounds and agents were injected once every four days intraperitoneally (i.p.) for 36 days. Treatment with 120 mg/kg of rutin or with 120 μg/kg of vinblastine resulted in a reduction of tumor weight and volume when compared with the control groups. Tumor size in xenograft mice treated with 120 mg/kg of rutin was significantly smaller than that in the untreated-control group. These novel findings indicate that rutin inhibits tumor growth in a xenograft animal model. Rutin may be useful in treating leukemia but certainly much more research is needed. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.
Environmental Toxicology 01/2011; 27(8):480-4. · 2.41 Impact Factor
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ABSTRACT: This study examined the effects of needle-free electroacupuncture, at ST36 on postoperative pain following hysterectomy. Based on a double-blind, sham and different intervention controlled clinical experimental design, 47 women were randomly allocated to four different groups. Except for those in the control group (Group 1, n = 13), a course of treatment was given of either sham (Group 2, n = 12), high-frequency stimulation (Group 3, n = 12), or low-frequency stimulation (Group 4, n = 10). All groups were assessed during the postoperative period for 24 hours. The Visual Analogue Scale was used to determine the amount of perceived pain felt by each subject. Differences were found between the means postoperatively at three, four, eight, 16 and 24 hours. Post hoc comparison tests indicated that Group 4 was significantly different from Groups 1, 2, and 3 at 24 hours. A one-way ANOVA analysis for total patient-controlled analgesia demand and doses indicated significant differences between the groups F(3, 42) = 3.59, P < .05. Post hoc analysis confirmed the differences between Groups 1 (M = 84.54) and 4 (M = 41.60). Treatment outcomes of this therapy showed a positive effect for the management of postoperative pain.
Evidence-based Complementary and Alternative Medicine 01/2011; 2011:696754. · 4.77 Impact Factor
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Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists. 12/2010; 48(4):194-5.
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ABSTRACT: A 40-year-old woman without remarkable medical history received epidural anesthesia for uterine cervix conization. Six hours after the operation, cauda equina syndrome occurred. Magnetic resonance imaging of the spine revealed epidural fluid accumulation around L5, as well as L4/5 herniated intervertebral disc found incidentally. Surgical decompression was performed with H-reflex monitoring. Epidural injection could result in cystic accumulation complicated with cauda equina syndrome.
Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists. 09/2010; 48(3):148-51.
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ABSTRACT: We report a 27-year-old hemostatically competent female scheduled for partial hepatectomy. During the operation, she experienced an accidental inferior vena cava tear and suffered acute blood loss. After fluid resuscitation and blood transfusion, she developed hypothermia, with a temperature of 33.8 degrees C, and severe coagulopathy with activated clotting time exceeding 1500 seconds measured using the Hemochron Response system (ITC, Edison, NJ, USA). Despite sufficient blood transfusion and correction of her electrolyte imbalance, the poor hemostasis persisted. After per-forming peritoneal lavage with warm saline, her condition dramatically improved and her hypothermia and severe coagulopathy were reversed.
Acta anaesthesiologica Taiwanica : official journal of the Taiwan Society of Anesthesiologists. 06/2010; 48(2):103-6.
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ABSTRACT: Amniotic fluid embolism occurs rarely but is a leading cause of maternal mortality. Regardless of emergent supportive medical treatment, it is associated with a very high mortality rate. Here, we present the case of a 33-year-old pregnant woman with amniotic fluid embolism, who sustained cardiac arrest and was rescued with early application of extracorporeal membrane oxygenation. The management of amniotic fluid embolism is to initially focus on rapid cardiopulmonary stabilization. Hemodynamic decompensation may be transient and recoverable within a few hours. Early application of extracorporeal membrane oxygenation should be considered in patients who are unresponsive to medical therapy before severe organ damage supervenes.
Acta Anaesthesiologica Taiwanica 07/2009; 47(2):99-102.
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BJA British Journal of Anaesthesia 06/2009; 102(5):720-1. · 4.24 Impact Factor
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ABSTRACT: Epidural patient-controlled analgesia (EPCA) and intravenous patient-controlled analgesia (IVPCA) have been used widely in parturients after cesarean section. Although many studies have demonstrated the safety and effectiveness of both EPCA and IVPCA, their effects on bowel activity of patients who have undergone cesarean section delivery have not yet been investigated. The purpose of this study was to compare the effect of EPCA and IVPCA on bowel activity after cesarean section.
We collected data from 726 parturients who consented to receive either EPCA or IVPCA for postoperative analgesia following cesarean section delivery. All patients used postoperative PCA for at least 2 days. The analgesic solution for EPCA was 0.05% bupivacaine plus fentanyl (3 microg/mL), and that for IVPCA was 0.1% morphine. The patients were assessed by visual analog pain scale (VAS) scores at rest and in a dynamic state, time to first flatus passage after the surgery, and overall satisfaction after completion of the PCA course. Student's t test was used to determine intergroup differences.
There were statistically significant differences between the EPCA and IVPCA groups in the time to first flatus passage, overall satisfaction and VAS scores at rest and in a dynamic state. Patients in the EPCA group had a shorter time to first flatus passage, higher overall satisfaction and lower VAS scores. In addition, regional anesthesia offered an apparently shorter time to first flatus passage in comparison with general anesthesia.
PCA is safe and effective in alleviating postoperative pain following cesarean section. EPCA offers a faster return of bowel activity, lower VAS scores, and better patient satisfaction than IVPCA.
Acta Anaesthesiologica Taiwanica 04/2009; 47(1):22-7.
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ABSTRACT: In many countries, general anesthesia is not routinely used for colonoscopic polypectomy in children because of either feasibility or cost-effectiveness issues. However, we have been using general anesthesia for colonoscopic polypectomy in pediatric patients in our hospital for the past 5 years. The aim of this study was to evaluate the safety of the procedure and the degree of satisfaction that the patients' parents and endoscopists had with the use of general anesthesia. We retrospectively analyzed the results of colonoscopic polypectomies under general anesthesia in 18 patients performed between January 2001 and December 2005. The removed polyps were examined histologically and the patients were observed to assess complications during the first 24-hour postoperative period. The patients' parents' and endoscopists' satisfaction with the use of general anesthesia was surveyed after the procedure. In our patient group, there were 10 boys and eight girls. The mean age was 5.5 +/- 3.4 years (range, 2-15 years). Seventeen of the 18 patients had rectal bleeding (mean duration, 3.7 months) as the main symptom. There were 12 patients with juvenile polyps, four with hyperplastic polyps, one with juvenile polyposis and one with Peutz-Jeghers syndrome. The majority (70.6%) of the polyps were located in the rectosigmoid colon. No significant complications related to colonoscopic polypectomy or anesthesia were observed. Satisfaction among parents and endoscopists ranged from good to excellent. General anesthesia is recommended for pediatric patients undergoing colonoscopic polypectomy.
The Kaohsiung journal of medical sciences 03/2009; 25(2):70-6. · 0.61 Impact Factor
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Rick Sai-Chuen Wu
Acta Anaesthesiologica Taiwanica 10/2008; 46(3):97-9.
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ABSTRACT: Hypertension and fluctuations in blood pressure (BP) during lumbar spinal surgery in the prone position under anesthesia are not unusual. The purpose of this study was to investigate the causes of the decrease in BP during lumbar spinal surgery in the prone position using a noninvasive monitor of cardiac output.
Twenty ASA Class I or II patients, scheduled for elective lumbar spinal surgery in the prone position, had their hemodynamic status monitored by a BioZ.com system Impedance Cardiograph during anesthesia. Hemodynamic data (heart rate [HR], mean BP, cardiac index [CI], stroke volume [SV] and systemic vascular resistance [SVR]) were registered at baseline, post-induction of general anesthesia, 10 minutes after the patient was turned from the supine to the prone position and 1 hour after the start of surgery. Friedman's test and the paired t test were used to compare the collected data on hemodynamic parameters.
The mean BP, SV, CI and HR were found to have significant differences (p < 0.05) at the designated time points as analyzed by Friedman's test, while the SVR and central venous pressure showed no significant changes. CI and SV were found to be markedly decreased from 2.4 +/- 0.3 to 2.0 +/- 0.3 L/minute/m2 and from 45.8 +/- 9.7 to 36.7 +/- 9.2 mL, respectively, after patients assumed the prone position. Mean BP also decreased significantly. After 1 hour of surgery, the mean BP decreased further with a fall in HR but the SV remained unchanged.
Decreases in SV and CI are the main causes of a decrease in BP in the prone position during lumbar spinal surgery.
Acta Anaesthesiologica Taiwanica 07/2008; 46(2):57-60.
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ABSTRACT: Syndrome of inappropriate secretion of antidiuretic hormone and diabetes insipidus occurring in very short order in the same patient is rare. We report a 9 month-old male infant suffering form holoprosencephaly developed syndrome of inappropriate secretion of antidiuretic hormone followed by diabetes insipidus within a relative short time postoperatively after his third operation. Inability to suppress as well as to stimulate arginine vasopressin secretion and anesthetic and surgical stresses, were thought to be the possible causes of this event.
Acta Anaesthesiologica Taiwanica 07/2007; 45(2):121-5.
