• Title/Summary/Keyword: Molecular Flow

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Hemodynamic Outcome of Successful Bypass Surgery in Patients with Atherosclerotic Cerebrovascular Disease: A study with Acetazolamide and $^{99m}Tc-ECD$ SPECT (죽상경화성 뇌혈관질환 환자에서 성공적인 EC/IC 우회술 후 혈류역학적 변화: 기저/아세타졸아미드 SPECT를 이용한 연구)

  • Eo, Jae-Seon;Oh, Chang-Wan;Kim, Yu-Kyeong;Park, Eun-Kyung;Lee, Won-Woo;Kim, Sang-Eun
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.6
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    • pp.293-301
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    • 2006
  • Purpose: The aim of the study was to evaluate the hemodynamic changes after successful bypass surgery in patients with atherosclerotic stenosis in ICA using $^{99m}Tc-ECD$ SPECT. Materials and Methods: Fourteen patients (M:F=8:6, mean age; $60{\pm}9$ years) who underwent STA-MCA anastomosis for unilateral atherosclerotic cerebrovascular disease were enrolled. $^{99m}Tc-ECD$ basal/acetazolamide perfusion SPECT studies were performed before, 10 days and 6 months after bypass surgery. Perfusion reserve was defined as the % changes after acetazolamide over rest image. Regional cerebral blood flow and perfusion reserve were compared preoperative, early-postoperative and late-postoperative scans. Results: The mean resting perfusion and decrease in perfusion reserve in affected ICA territory on preoperative scan was $52.4{\pm}3.5\;and\;-7.9{\pm}4.7%$, respectively. The resting perfusion was significantly improved after surgery on early-postoperative scan (mean $53.7{\pm}2.7$) and late-postoperative scan (mean $53.3{\pm}2.5$) compared with preoperative images (p<0.05, respectively). Resting perfusion did not showed further improvement on late-postoperative scan compared with early-postoperative scan. The perfusion reserve was $-3.7{\pm}2.6%$ on early-postoperative scan, and $-1.6{\pm}2.3%$ on late-postoperative scan, which was significantly improved after surgery. Additionally, further improvement of perfusion reserved as observed on late-postoperative scan (p<0.05). While, in the unaffected ICA territory, no significant changes in the resting perfusion and perfusion reserve was observed. Conclusion: The improvement of resting perfusion and perfusion reserve in early-postoperative scan reflects the immediate restoration of the cerebral blood flow by bypass surgery. In contrasts, further improvement of perfusion reserve showing on late-postoperative scan may indicate a good collateral development after surgery, which may indicate good surgical outcome after surgery.

Radiation-induced Apoptosis is Differentially Modulated by PTK Inhibitors in K562 Cells (K562 백혈병 세포주에서 방사선에 의해 유도되는 Apoptosis에 미치는 PTK Inhibitors의 영향)

  • Lee Hyung Sik;Moon Chang Woo;Hur Won Joo;Jeong Su Jin;Jeong Min Ho;Lee Jeong Hyeon;Lim Young kin;Park Heon Joo
    • Radiation Oncology Journal
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    • v.18 no.1
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    • pp.51-58
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    • 2000
  • Purpose :The effect of PTK inhibitors (herbimycin A and genistein) on the induction of radiation-induced apoptosis in Ph-positive KS62 leukemia cell line was investigated. Materials and Methods :K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For 6 MV X-ray irradiation and drug treatment, cultures were initiated at 2×106 cells/mL. The cells were irradiated with 10 Gy. Stock solutions of herbimycin A and genistein were prepared in dimethyl sulphoxide (DMSO). After incubation at 37$^{\circ}C$ for 0$\~$48 h, the extent of apoptosis was determined using agarose gel electrophoresis and TUNEL assay. The progression of cells through the cell cycle after irradiation and drug treatment was also determined with flow cytometry. Western blot analysis was used to monitor bel-2, bel-X$_{L}$ and bax protein levels. Results :Treatment with 10 Gy X-irradiation did not result in the induction of apoptosis. The HMA alone (500 nM) also failed to induce apoptosis. By contrast, incubation of K562 cells with HMA after irradiation resulted in a substantial induction of nuclear condensation and fragmentation by agarose gel electro-phoresis and TUNEL assay. Genistein failed to enhance the ability of X-irradiation to induce DNA fragmentation. Enhancement of apoptosis by HMA was not attributable to downregulation of the bel-2 or bel-X$_{L}$ anti-apoptotic proteins. When the cells were irradiated and maintained with HMA, the percentage of cells in G2/M phase decreased to 30$\~$40$\%$ at 48 h. On the other hand, cells exposed to 10 Gy X-irradiation alone or maintained with genistein did not show marked cell cycle redistribution. Conclusion : We have shown that nanomolar concentrations of the PTK inhibitor HMA synergize with X-irradiation in inducing the apoptosis in Ph (+) K562 leukemia cell line. While, genistein, a PTK inhibitor which is not selective for p210$^{bcr/abl}$ failed to enhance the radiation induced apoptosis in KS62 cells. It is unlikely that the ability of HMA to enhance apoptosis in K562 cells is attributable to bel-2 family. It is plausible that the relationship between cell cycle delays and cell death is essential for drug development based on molecular targeting designed to modify radiation-induced apoptosis.

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The Modulation of Radiosensitivity by Combined Treatment of Selective COX-2 Inhibitor, NS 398 and EGF Receptor Blocker AG 1478 in HeLa Cell Line (선택적 COX-2 억제제 NS 398과 EGF 수용체 차단제 AG 1478의 복합투여가 HeLa 세포주의 방사선 감수성에 미치는 영향)

  • Youn Seon Min;Oh Young Kee;Kim Joo Heon;Park Mi Ja;Seong In Ock;Kang Kimun;Chai Gyuyong
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.51-60
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    • 2005
  • Purpose : Selective inhibition of multiple molecular targets may improve the antitumor activity of radiation. Two specific inhibitors of selective cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) were combined with radiation on the HeLa cell line. To investigate cooperative mechanism with selective COX-2 inhibitor and EGFR blocker, in vitro experiments were done. Materials and Methods : Antitumor effect was obtained by growth inhibition and apoptosis analysis by annexin V-Flous method. Radiation modulation effects were determined by the clonogenic cell survival assay. Surviving fractions at 2 Gy ($SF_2$) and dose enhancement ratio at a surviving fraction of 0.25 were evaluated. To investigate the mechanism of the modulation of radiosensitivity, the cell cycle analyses were done by flow cytometry. The bcl-2 and bax expressions were analyzed by western blot. Results : A cooperative effect were observed on the apoptosis of the HeLa ceil line when combination of the two drugs, AG 1478 and NS 398 with radiation at the lowest doses, apoptosis of $22.70\%$ compare with combination of the one drug with radiation, apoptosis of $8.49\%$. In cell cycle analysis, accumulation of cell on $G_0/G_l$ phase and decrement of S phase fraction was observed from 24 hours to 72 hours after treatment with radiation, AG 1478 and NS 398. The combination of NS 398 and AG 1478 enhanced radiosensitivity on a concentration-dependent manner in HeLa cells with dose enhancement ratios of 3.00 and $SF_2$ of 0.12 but the combination of one drug with radiation was not enhanced radlosensitivity with dose enhancement ratios of 1.12 and SF2 of 0.68 (p=0.005). The expression levels of bcl-2 and bax were reduced when combined with AG 1478 and NS 398. Conclusion : Our results indicate that the selective COX-2 inhibitor and EGFR blocker combined with radiation have potential additive or cooperative effects on radiation treatment and may act through various mechanisms including direct inhibition of tumor cell proliferation, suppression of tumor cell cycle progression and inhibition of anti-apoptotic proteins.

Principle and Recent Advances of Neuroactivation Study (신경 활성화 연구의 원리와 최근 동향)

  • Kang, Eun-Joo
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.2
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    • pp.172-180
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    • 2007
  • Among the nuclear medicine imaging methods available today, $H_2^{15}O-PET$ is most widely used by cognitive neuroscientists to examine regional brain function via the measurement of regional cerebral blood flow (rCBF). The short half-life of the radioactively labeled probe, $^{15}O$, often allows repeated measures from the same subjects in many different task conditions. $H_2^{15}O-$ PET, however, has technical limitations relative to other methods of functional neuroimaging, e.g., fMRI, including relatively poor time and spatial resolutions, and, frequently, insufficient statistical power for analysis of individual subjects. However, recent technical developments, such as the 3-D acquisition method provide relatively good image quality with a smaller radioactive dosage, which in turn results in more PET scans from each individual, thus providing sufficient statistical power for the analysis of individual subject's data. Furthermore, the noise free scanner environment $H_2^{15}O$ PET, along with discrete acquisition of data for each task condition, are important advantages of PET over other functional imaging methods regarding studying state-dependent changes in brain activity. This review presents both the limitations and advantages of $^{15}O-PET$, and outlines the design of efficient PET protocols, using examples of recent PET studies both in the normal healthy population, and in the clinical population.

Extract from Eucheuma cottonii Induces Apoptotic Cell Death on Human Osteosarcoma Saos-2 Cells via Caspase Cascade Apoptosis Pathway (Eucheuma cottonii 추출물에 의한 인체 골육종암 Saos-2 세포의 자가사멸 유도)

  • Kang, Chang-Won;Kang, Min-Jae;Kim, Kyong Rok;Kim, Nan-Hee;Seo, Yong Bae;Kang, Keon-Hee;Kim, Sang-Ho;Kim, Gun-Do
    • Journal of Life Science
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    • v.26 no.2
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    • pp.147-154
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    • 2016
  • Osteosarcoma (OS) is the most common and malignant bone tumors. Although many types of resection surgery and experimental agents were developed, median survival and clinical prognosis are poorly investigated. Recently, several researches have reported that Eucheuma cottonii has potent as protective effects of coal dust-induced lung damage via inhibition of malondialdehyde (MDA) and oxidative stress in bronchoalveolar lavage fluids (BALF). However, anti-cancer effects and specific molecular mechanism of extract from Eucheuma cottonii (EE) has not been clearly studied yet. This study evaluated that anti-cancer potential of EE in human osteosarcoma Saos-2 cells. EE indicated cytotoxicity on Saos-2 cells in a dose-dependent manner. Morphological degradation and nucleic condensation were also observed under the EE treatment. However, it did not significantly affect on non-cancerous kidney HEK-293 cells under the same concentration which is shown cytotoxicity on Saos-2 cells. The phosphorylation of Fas-Associated Death Domain (FADD) and expression of cleaved caspase-8, -7 and -3 were upregulated in a dose-dependent manner. In immunofluorescence staining, expression level of Fas and cleaved PARP were upregulated by EE treatment. Furthermore, treatment of EE induces upregulation of sub G1 phase by flow cytometry analysis. The results demonstrated that EE has a therapeutic potential against osteosarcoma via FADD mediated caspase cascade apoptosis signal pathway.

Effect of Repetitive Transcranial Magnetic Stimulation in Drug Resistant Depressed Patients (치료 저항성 우울증 환자에서 반복적 경두개 자기자극후 국소뇌혈류 변화)

  • Chung, Yong-An;Yoo, Ie-Ryung;Kang, Bong-Joo;Chae, Jeong-Ho;Lee, Hye-Won;Moon, Hyun-Jin;Kim, Sung-Hoon;Sohn, Hyung-Sun;Chung, Soo-Kyo
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.1
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    • pp.9-15
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    • 2007
  • Purpose: Repetitive transcranial magnetic stimulation (rTMS) has recently been clinically applied in the treatment of drug resistant depressed patients. There are mixed findings about the efficacy of rTMS on depression. Furthermore, the influence of rTMS on the physiology of the brain is not clear. We prospectively evaluated changes of regional cerebral blood flow (rCBF) between pre- and post-rTMS treatment in patients with drug resistant depression. Materials and Methods: Twelve patients with drug-resistant depression (7 male, 5 female; age range: $19{\sim}52$ years; mean age: $29.3{\pm}9.3$ years) were given rTMS on right prefrontal lobe with low frequency (1 Hz) and on left prefrontal lobe with high frequency (20 Hz), with 20-minute-duration each day for 3 weeks. Tc-99m ECD brain perfusion SPECT was obtained before and after rTMS treatment. The changes of cerebral perfusion were analyzed using statistical parametric mapping (SPM; t=3.14, uncorrected p<0.01, voxel=100). Results: Following areas showed significant increase in rCBF after 3 weeks rTMS treatment: the cingulate gyrus, fusiform gyrus of right temporal lobe, precuneus, and left lateral globus pallidus. Significant decrement was noted in: the precental and middle frontal gyrus of right frontal lobe, and fusiform gyrus of left occipital lobe. Conclusion: Low-frequency rTMS on the right prefrontal cortex and high-frequency rTMS on the left prefrontal cortex for 3 weeks as an add-on regimen have increased and decreased rCBF in the specific brain regions in drug-resistant depressed patients. Further analyses correlating clinical characteristics and treatment paradigm with functional imaging data may be helpful in clarifying the pathophysiology of drug-resistant depressed patients.

Compilation of 104 Experimental Theses on the Antitumor and Immuno-activating therapies of Oriental Medicine (한의학의 항종양 면역치료에 관한 연구 -1990년 이후 발표된 실험논문을 중심으로-)

  • Kang Yeon Yee;Kim Tai Im;Park Jong Ho;Kim Sung Hoon;Park Jong Dai;Kim Dong Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.1-24
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    • 2003
  • This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

Purification and Characterization of a Lipolytic Enzyme Produced by Aeromonas hydrophila PL43 (Aeromonas hydrophila PL43이 생산하는 지질분해 효소의 정제 및 특성)

  • Kim, Yong-Woo;Hong, Sung Wook;Chung, Kun Sub
    • Microbiology and Biotechnology Letters
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    • v.44 no.2
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    • pp.130-139
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    • 2016
  • A bacterial strain, producing an excellent lipolytic enzyme, was isolated from the intestinal tracts of an earthworm (Eisenia fetida). The strain was identified as Aeromonas hydrophila by phenotypic, chemotaxonomic characteristics and 16S ribosomal DNA analysis, and was designated as Aeromona hydrophila PL43. The lipolytic enzyme from A. hydrophila PL43 was purified via 35−45% ammonium sulfate precipitation, DEAE-sepharose fast flow ion-exchange, and sephacryl S-300HR gel filtration chromatography. The yield of the purified enzyme was 3.7% and 2.5% of the total activity of crude extracts with p-nitrophenyl butyrate (pNPB) and p-nitrophenyl palmitate (pNPP) as substrates, respectively. The molecular weight of the purified enzyme was approximately 74 kDa using gel filtration, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and zymography. The optimal activity of purified enzyme was observed at 50℃ and pH 8.0 using pNPB, and 60℃ and pH 8.0 using pNPP. The purified enzyme was stable in the ranges 20− 60℃ and pH 7.0−10.0. The activity of purified enzyme was inhibited by PMSF, pepstatin A, Co2+, Cu2+, and Fe2+, but was recovered by metal chelating of EDTA. The Km and Vmax values of the purified enzyme were 1.07 mM and 7.27 mM/min using pNPB and 1.43 mM and 2.72 mM/min using pNPP, respectively.

Petrochemical study on the Daejeon-sa basalt in the Mt. Juwang area, Cheongsong (청송 주왕산지역 대전사 현무암의 암석화학적 연구)

  • 윤성효;이문원;고정선;김영라;안지영
    • The Journal of the Petrological Society of Korea
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    • v.9 no.2
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    • pp.84-98
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    • 2000
  • Daejeon-sa basalt in the Mt. Juwang area composed of 12 basalt flows alternate with 9 peperites and each basalt and peperite has the variety of thickness. Peperites yielded in Daejeon-sa basalt are mixed of basalt with reddish shale, of which textural type is globular peperite. Basalts yielded in Daejeon-sa basalt are massive basalt without vesicule, although sometimes vesicules are founded in upper within a flow unit. The basalt has mainly pseudomorph of olivine as phenocryst, and also plagioclase and clinopyroxene phenocryst. Matrix is mainly subophitic texture. The plotting result on the TAS diagram shows these basalts belong to the sub-alkaline, and it can be subdivided into calc-alkaline series on the basis of the diagram of Si02 vs. K20 and of alkali index vs. A1203 diagram. According to plots of wt.% oxides vs. wt.% MgO, abundances of A1203 and CaO increase with decreasing MgO while F ~ dOecre~ase . With decreasing MgO compatible elements decrease while incompatible elements increase. In spider diagram of MORB-normalized trace element patterns, HFS elements are nearly similiar with MORB, but LIL elements are enriched. Especially, contents of Ce, F: and Sm are enriched but Nb is depleted. In the chondrite-normalized REE patterns light REEs are enriched than heavy REEs. Tectomagmatic discrimination diagrams shows basalts in the study area are formed in the tectonomagmatic environment of subduction zone under continental margin. This result accord with characters of chemical composition mentioned above. Cr vs. Y diagram and CeM, vs. Ce diagram show that the primary magma of the basalts may formed by the about 15% partial melting of garnet-peridotite in the mantle wedge. After then, Daejeon-sa basalts may formed from evolved magma undergone mainly olivine fractional crystallization and contarnination of crustal materials before eruption.

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Induction of G2/M Arrest and Apoptosis by the Methanol Extract of Typha orientalis in Human Colon Adenocarcinoma HT29 Cells (포황 메탄올 추출물에 의한 인체 대장암 세포주 HT29의 G2/M Arrest 및 Apoptosis 유발)

  • Jin, Soojung;Yun, Seung-Geun;Oh, You Na;Lee, Ji-Young;Park, Hyun-Jin;Jin, Kyong-Suk;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.41 no.4
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    • pp.425-432
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    • 2013
  • Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.