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Silibinin Inhibits Proliferation, Induces Apoptosis and Causes Cell Cycle Arrest in Human Gastric Cancer MGC803 Cells Via STAT3 Pathway Inhibition

  • Wang, Yi-Xin;Cai, Hong;Jiang, Gang;Zhou, Tian-Bao;Wu, Hai
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6791-6798
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    • 2014
  • Background: To investigate the effect of silibinin on proliferation and apoptosis in human gastric cancer cell line MGC803 and its possible mechanisms. Materials and Methods: Human gastric cancer cell line MGC803 cells were treated with various concentration of silibinin. Cellular viability was assessed by CCK-8 assay andapoptosis and cell cycle distribution by flow cytometry. Protein expression and mRNA of STAT3, and cell cycle and apoptosis regulated genes were detected by Western blotting and real-time polymerase chain reaction, respectively. Results: Silibinin inhibits growth of MGC803 cells in a dose- and time-dependent manner. Silibinin effectively induces apoptosis of MGC803 cells and arrests MGC803 cells in the G2/M phase of the cell cycle, while decreasing the protein expression of p-STAT3, and of STAT3 downstream target genes including Mcl-1, Bcl-xL, survivin at both protein and mRNA levels. In addition, silibinin caused an increase in caspase 3 and caspase 9 protein as well as mRNA levels. Silibinin caused G2/M phage arrest accompanied by a decrease in CDK1 and Cyclin B1 at protein and mRNA levels.. Conclusions: These results suggest that silibinin inhibits the proliferation of MGC803 cells, and it induces apoptosis and causes cell cycle arrest by down-regulating CDK1, cyclinB1, survivin, Bcl-xl, Mcl-1 and activating caspase 3 and caspase 9, potentially via the STAT3 pathway.

Trichostatin A-induced Apoptosis is Mediated by Krüppel-like Factor 4 in Ovarian and Lung Cancer

  • Zohre, Sadeghi;Kazem, Nejati-Koshki;Abolfazl, Akbarzadeh;Mohammad, Rahmati-Yamchi;Aliakbar, Movassaghpour;Effat, Alizadeh;Zahra, Davoudi;Hassan, Dariushnejad;Nosratollah, Zarghami
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6581-6586
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    • 2014
  • Background: The istone deacetylase (HDAC) inhibitor trichostatin A (TSA) is known to mediate the regulation of gene expression and antiproliferation activity in cancer cells. Kr$\ddot{u}$ppel-like factor 4 (klf4) is a zinc finger-containing transcription factor of the SP/KLF family, that is expressed in a variety of tissues and regulates cell proliferation, differentiation, tumorigenesis, and apoptosis. It may either either function as a tumor suppressor or an oncogene depending on genetic context of tumors. Aims: In this study, we tested the possibility that TSA may increase klf4 expression and cancer cell growth inhibition and apoptosis in SKOV-3 and A549 cells. Materials and Methods: The cytotoxicity of TSA was determined using the MTT assay test, while klf4 gene expression was assessed by real time PCR andto ability of TSA to induce apoptosis using a Vybrant Apoptosis Assay kit. Results: Our results showed that TSA exerted dose and time dependent cytotoxicity effect on SKOV-3 and A549 cells. Moreover TSA up-regulated klf4 expression. Flow cytometric analysis demonstrated that apoptosis was increased after TSA treatment. Conclusions: Taken together, this study showed that TSA increased klf4 expression in SKOV3 and A549 cell lines, consequently, klf4 may played a tumor-suppressor role by increasing both cell growth inhibition and apoptosis. This study sheds light on the details of molecular mechanisms of HDACI-induced cell cycle arrest and apoptosis.

siRNA-mediated Silencing of Survivin Inhibits Proliferation and Enhances Etoposide Chemosensitivity in Acute Myeloid Leukemia Cells

  • Karami, Hadi;Baradaran, Behzad;Esfahani, Ali;Estiar, Mehrdad Asghari;Naghavi-Behzad, Mohammad;Sakhinia, Masoud;Sakhinia, Ebrahim
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7719-7724
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    • 2013
  • Background: Overexpression of survivin, a known inhibitor of apoptosis, is associated with tumor progression and drug resistance in numerous malignancies, including leukemias. The aim of this study was to investigate the effect of a specific survivin small interference RNA (siRNA) on proliferation and the sensitivity of HL-60 acute myeloid leukemia (AML) cells to the chemotherapeutic drug etoposide. Materials and Methods: The cells were transfected with siRNAs using Lipofectamine $^{TM}2000$ transfection reagent. Relative survivin mRNA and protein levels were measured by quantitative real-time PCR and Western blotting, respectively. Trypan blue exclusion assays were performed to monitor tumor cell proliferation after siRNA transfection. The cytotoxic effects of etoposide and survivin siRNA, alone and in combination, on leukemic cells were determined using MTT assay. Apoptosis was assessed by ELISA cell death assay. Results: Survivin siRNA markedly reduced both mRNA and protein expression levels in a time-dependent manner, leading to distinct inhibition of cell proliferation and increased spontaneous apoptosis. Surprisingly, survivin siRNA synergistically increased the cell toxic effects of etoposide. Moreover, survivin down-regulation significantly enhanced its induction of apoptosis. Conclusions: Our study suggests that down-regulation of survivin by siRNA can trigger apoptosis and overcome drug resistance of leukemia cells. Therefore, survivin siRNA may be an effective adjuvant in AML chemotherapy.

Influence of Tacrine on Catecholamine Secretion in the Perfused Rat Adrenal Gland

  • Jang, Seok-Jeong;Yang, Won-Ho;Lim, Dong-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.4
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    • pp.207-214
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    • 2002
  • The present study was designed to clarify whether tacrine affects the release of catecholamines (CA) from the isolated perfused model of rat adrenal gland or not and to elucidate the mechanism of its action. Tacrine $(3{\times}10^{-5}{\sim}3{\times}10^{-4}\;M)$ perfused into an adrenal vein for 60 min inhibited CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M),$ DMPP (a selective neuronal nicotinic agonist, $10^{-4}$ M for 2 min) and McN-A-343 (a selective muscarinic M1-agonist, $10^{-4}$ M for 2 min) in relatively dose- and time- dependent manners. However, tacrine failed to affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M).$ Tacrine itself at concentrations used in the present experiments did not also affect spontaneous CA output. Furthermore, in the presence of tacrine $(10^{-4}\;M),$ CA secretory responses evoked by Bay-K-8644 (an activator of L-type $Ca^{2+}$ channels, $10^{-4}\;M),$ but not by cyclopiazonic acid (an inhibitor of cytoplasmic $Ca^{2+}-ATPase,\;10^{-4}\;M),$ was relatively time-dependently attenuated. Also, physostigmine $10^{-4}\;M),$ given into the adrenal gland for 60 min, depressed CA secretory responses evoked by ACh, McN-A-343 and DMPP while did not affect that evoked by high $K^+.$ Collectively, these results obtained from the present study demonstrate that tacrine greatly inhibits CA secretion from the perfused rat adrenal gland evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by direct membrane-depolarization. It is suggested that this inhibitory effect of tacrine may be exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells without $Ca^{2+}$ release from the cytoplasmic calcium store, that is relevant to the cholinergic blockade. Also, the mode of action between tacrine and physostigmine in rat adrenomedullary CA secretion seems to be similar.

Photonic Microwave Notch Filter with Negative Coefficient Using Reflective Semiconductor Optical Amplifier (반사형 반도체 광 증폭기를 이용한 음계수를 가지는 광 마이크로파 노치 필터)

  • Kwon, Won-Bae;Choi, Yong-Kyu;Kim, Junsu;Kim, Kyung-Ho;Jeong, Min-A;Lee, Seong Ro;Park, Chang-Soo
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.39C no.5
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    • pp.418-424
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    • 2014
  • We propose and experimentally demonstrate a photonic microwave notch filter with a negative coefficient. The negative coefficient is obtained by using cross gain modulation (XGM) in a reflective semiconductor optical amplifier (RSOA). When the RSOA is operated in saturated region, the signal carried on the pump wavelength is inversely copied to the probe wavelength by the XGM effect, showing a negative coefficient. Time delay between pump signal and probe signal is provided by single mode fiber (SMF) with wavelength dependent time delay. The proposed microwave notch filter shows notch dips of more than 35.1 dB and free spectral range (FSR) of about 380.6 MHz.

Antihyperglycemic Effect of Water Extracts from Pleurotus cornucopiae-Containing α-Glucosidase Inhibitor (α-Glucosidase 저해물질을 함유한 노랑느타리버섯 (Pleurotus cornucopiae) 물추출물의 혈당상승 억제 효과)

  • Shin, Ja-Won;Bae, Sang-Min;Han, Sang-Min;Lee, Yun-Hae;Jeong, Youn-Kyung;Ji, Jeong-Hyun;Lee, Jong-Soo
    • The Korean Journal of Mycology
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    • v.44 no.1
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    • pp.57-60
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    • 2016
  • Following preparation of water extracts of Pleurotus cornucopiae fruiting body-containing ${\alpha}$-glucosidase inhibitor, their antihyperglycemic effects were examined using streptozotocin-induced diabetic Sprague-Dawley (SD)-rats. The water extracts from Pleurotus cornucopiae showed dosage-dependant antihyperglycemic effects on the streptozotocin-induced diabetic SD-rats after oral administration to 120 min on the short time test and 4 days on the long time test, respectively. The water extracts from Pleurotus cornucopiae fruiting body showed dosage-dependent hypoglycemic action after administration to 120 min and 4 days in the SD-rat and streptozotocin-induced diabetic SD-rat.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

  • Kim, Young Eun;Choi, Hyung Chul;Lee, In-Chul;Yuk, Dong Yeon;Lee, Hyosung;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.572-580
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    • 2016
  • 3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.

An Effect of the Eddy Intrusive Transport Variations Across the Shelfbreak on the Korea Strait and the Yellow sea Part 1 : Barotropic Model Study (대륙붕사면에서의 에디 유입에 의한 해수수송량 변화가 대한해협 및 황해에 미치는 영향 제1부 : 순압 모델 연구)

  • YOO, KWANG WOO;OH, IM SANG
    • 한국해양학회지
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    • v.28 no.4
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    • pp.281-291
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    • 1993
  • A time-dependent primitive two0dimensional calculation is conducted to investigate the variations of Vol. transport onto the Yellow Sea and the Korea Strait with real bathymetries and to tract the Lagrangian movement of water particles. A series of experiment of the barotropic Kuroshio intrusions shows that the eddy induced branching of Kuroshio has sufficient intensity as to modify the continental shelf circulation. This intrusion seems to be one of the important forcing terms such as winds. tides and buoyancy that can also affect the dynamics in the region of the continental shelf. Transport variations across the shelfbreak due to the branching of Kuroshio which come particularly from the southwest of the Kyushu Island, have a strong relationship with the transport variations across the Korea Strait and in the southern area of the Yellow sea. The particle trajectories of the model results are well agreed with the trajectories of satellite tracking drifters obtained by one of the WOCE/TOGA program except the longer travel time period in the present model.

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Berberine Hydrochloride Impact on Physiological Processes and Modulation of Twist Levels in Nasopharyngeal Carcinoma CNE-1 Cells

  • Li, Cai-Hong;Wu, Dong-Fang;Ding, Hang;Zhao, Yang;Zhou, Ke-Yuan;Xu, De-Feng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1851-1857
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    • 2014
  • Objective: The main purpose of this work was to investigate the effect of berberine hydrochloride (BH) on the proliferation, apoptosis, migration, and invasion of CNE-1 nasopharyngeal carcinoma cells. Our results shed light on the functional components of traditional Chinese herbs for potential use in modern medicine. Methods: The CNE-1 cell line was treated with different concentrations of BH and effects on cell viability and proliferation were evaluated using the Cell Counting Kit-8 (CCK-8) assay. Anti-migratory and anti-invasive actions of BH were investigated using wound healing assays and the Millicell Hanging cell culture insert system, respectively. Expression of the epithelial-mesenchymal transition (EMT)-related gene twist (Twist) was analyzed by real-time PCR and Western blotting. Apoptosis was estimated with an annexin-V fluorescein (FITC) apoptosis detection kit, as well as with reference to levels of activated caspase-3 of CNE-1 cells before and after treatment with BH utilizing fluorescence spectroscopy. Results: BH was capable of reducing proliferation and viability of CNE-1 cells in a dose- and time-dependent manner, also demonstrating anti-migratory and anti-invasive capacities which correlated with reduction in expression of Twist. Finally, BH was able to induce significant amounts of apoptosis in CNE-1 cells, as demonstrated by an increase in the activity of caspase-3 and in annexin-V staining following treatment. Conclusion: BH extracted from rhizoma coptidis demonstrated an ability to block proliferation, induce apoptosis, and impair the migration and invasion of the CNE-1 cell line Considering these properties, our results suggest that BH could be an important compound for consideration in the treatment of nasopharyngeal carcinoma.

The effect of hydropriming and explants on shoot initiation and tetraploids in small watermelons

  • Phat, Phanna;Noh, Jae Jong;Ju, Ho-Jong;Lee, Gi-An;Ma, Kyung-Ho
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.176-176
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    • 2017
  • Hydropriming had positive effects on the time for germination to reach 50%, the germination index, the time to final germination percentage, and the number of uniform seedlings with enlarged cotyledons in in vitro germination of small watermelon. In addition, the highest shoot initiation was obtained from hydroprimed cotyledonary nodes ($95{\pm}6%$), followed by non-primed cotyledonary nodes ($78{\pm}6%$), hydroprimed cotyledons ($72{\pm}4%$), and non-primed cotyledons ($48{\pm}4%$). Meanwhile, no shoots were initiated from hypocotyls. The total number of shoots that initiated from cotyledonary nodes and cotyledon explants was insignificant, indicating that both cotyledons and cotyledonary node were good sources for the in vitro culture. Choosing explant sources that favor tetraploidy should be the key for producing higher polyploidy plants; a total of 10.5% of tetraploid regenerants were entirely identified from cotyledon explants. Cotyledons with highly differentiated cells might show higher variations than cotyledonary nodes with more preexisting meristematic cells. Cells of cotyledon tissue might undergo changes in ploidy level during differentiation of the culture, or it might be that some of the variations were already present in the tissues of the donor plant. Morphological changes in fruit length of tetraploid regenerants are genotype-dependent.

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