• Title/Summary/Keyword: Apoptosis

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Anti-lymphoma Activities of Phlojodicarpus sibiricus and Artemisia kruhsiana Besser Extracts (Phlojodicarpus sibiricus와 Artemisia kruhsiana Besser 추출물의 항림프종 효과 분석)

  • Kim, Jisu;Kim, Dong Uk;Nam, Jehyun;Jeon, Byeol Eun;Okhlopkova, Zhanna M.;Zulfugarov, Ismayil S.;Kim, Sang-Woo
    • Journal of Life Science
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    • v.30 no.4
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    • pp.379-385
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    • 2020
  • Phlojodicarpus sibiricus and Artemisia kruhsiana Besser are medicinal plants traditionally used in Russia. Phlojodicarpus sibiricus extracts (PSE) have been shown to have anti-obesity properties, and Artemisia kruhsiana Besser extracts (AKBE) contain terpenoid compounds that exert various medicinal effects. Here, we investigated the potential pro-apoptotic effects of PSE and AKBE in diffuse large B-cell lymphoma (DLBCL) and elucidated the underlying mechanism. PSE and AKBE treatment of six DLBCL cell lines with various genetic abnormalities effectively reduced cell viability in a dose-dependent manner, while having a minimal impact on the survival of normal murine bone marrow cells and splenocytes. This suggests that the cytotoxic effects of PSE and AKBE are specific to DLBCL cells. Therefore, we expect limited side effects when these plant extracts are administered to DLBCL patients. Our JC-1 assays demonstrate that the pro-apoptotic effects of these plant extracts are produced by a reduction of anti-apoptotic Bcl-2 family members and, thereby, disruption of the mitochondrial membrane potential. Moreover, PSE and AKBE induce cell death independently of Myc, whose abnormalities are frequently observed in patients with DLBCL and are associated with poor prognosis. Our findings reveal hitherto uncharacterized pro-apoptotic effects of PSE and AKBE in DLBCL. Isolation of single compounds with anti-lymphoma activities should be pursued further.

Apoptotic Effects of Some Plants on MCF-7 Mammary Gland Adenocarcinoma Cells (수종식물의 MCF-7 세포에 대한 세포사 및 항ㆍ증식효과)

  • 정용자
    • Journal of Life Science
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    • v.14 no.1
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    • pp.61-66
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    • 2004
  • Many studies have been widely carried out to find out new compound having anti-cancer activity from animals and plants. Some plants have been reported to have anti-lancer effects. However, the anti-cancer effect of edible plants were seldomly evaluated. Therefore we investigated the anticancer effects of edible plants (10 samples) easily available around us by measuring number of survival cancer cells after treatment with direct cell counting and MTT analysis, and by examining the morphological change under the electromicroscope. Of the 10 samples tested, Equisetum arvense L., Lactuca dentata Mokino. var. faviflora Makino. showed moderate anti-cancer effects even at the concentration of 10 $\mul/ml$ against MCF-7 adenocarcinoma cell line. Of them, Capsicum annuum L. had most potent anti-cancer activity against MCF-7 adenocarcinoma cell line showing proliferation inhibited, morphological change and apoptosis at the concentration of 2 $\mul/ml$.

Analysis of the Correlation between Expressions of HSP90α, HSP90β, and GRP94, and the Clinicopathologic Characteristics in Tissues of Non-Small Cell Lung Cancer Patients (비소세포 폐암 환자 조직에서 Hsp90α, Hsp90β, GRP94의 발현과 임상병리학적 특성과의 상관관계 분석)

  • Kim, Mi Kyeong
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.4
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    • pp.460-469
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    • 2017
  • Heat shock proteins (HSPs) are induced as a self-defense mechanism of cells when exposed to various external stresses, such as high fever, infection, free radicals, and heavy metals. They affect the prognosis in the process of tumor formation. HSP is classified into four families: HSP27, HSP60, HSP90, and HSP100, depending on molecular weight. Heat shock protein 90 (HSP90), a molecular chaperone, plays an important role in the cellular protection against various stressful stimuli and in the regulation of cell cycle progression and apoptosis. In the present study, we assessed the differential expression of HSP90 family proteins in non-small cell lung cancer (NSCLC), and the correlation of their expression levels with clinicopathologic factors and patient survival rates. The result of this study can be summarized as follows; $HSP90{\alpha}$ showed higher expression in patients with no lymphovascular invasion (p=0.014). $HSP90{\beta}$ showed a higher expression of squamous cell carcinoma (p=0.003), and an over expression of glucose-related protein (GRP94) was significantly associated with poor differentiation (p=0.048). However, none of the HSP90 proteins showed a significant association with the survival status in patients with NSCLC. This study also indicates that $HSP90{\alpha}$ might contribute more to the carcinogenesis of NSCLC than $HSP90{\beta}$, and GRP94 and isoform selectivity should be considered when HSP90 inhibitors are studied or utilized in the treatment of NSCLC.

Purification and Characterization of Anticarcinogenic Compound from Corni fructus (산수유에 함유된 항암물질의 정제 및 특성)

  • Kim, Byeong-Hyeon;Park, Kyung-Wuk;Kim, Jae-Yong;Jeong, Ill-Yun;Yang, Gi-Ho;Cho, Young-Sook;Yee, Sung-Tae;Seo, Kwon-Il
    • Korean Journal of Food Science and Technology
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    • v.36 no.6
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    • pp.1001-1007
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    • 2004
  • Chloroform layer from methanol extract of Corni fructus (Cornaceae) showed strong antiproliferation effect on human cancer cell lines by SRB assay. Anticarcinogenic-active compound was isolated and purified by silica gel column and thin layer chromatograpies, and identified as ursolic acid ($3{\beta}$-hydroxyrus-12-ene-28-oic acid, MW:456) by mass and IR spectrophotometries, and $^1H-and\;^{13}C-NMRs$. The compound inhibited proliferation of A549 (human lung cancer cell line) and MCF-7 (human breast cancer cell line) cells in dose-dependant manner when treated for 48 hr. Inhibition rates of both cells were over 40% and 90% compared with control cells at the $30\;{\mu}g/mL\;and\;100\;{\mu}g/mL$, respectively. Morphology of cells treated with the compound for 15 hr at $10\;{\mu}g/mL$ was distorted with shrinked cell mass, and cell number was lower than that of control cells. Cell cycle analysis showed sub-G1 phase arrest in both cell lines following 15 hr exposure to the compound; % of cell phase increased to 11.7 and 11.2% compared to the control of 4.0% and 2.1% in A549 and MCP-7 cells, respectively.

The Effects of Cynanchi wilfordii Radix Ethanol Extracts upon Irradiated Rat's Blood and Organ (백하수오 에탄올추출물이 방사선조사에 따른 흰쥐의 혈구 및 장기에 미치는 영향)

  • Kim, Jang-Oh;Choi, Jun-Hyeok;Shin, Ji-Hye;Jung, Do-Young;Min, Byung-In
    • Journal of radiological science and technology
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    • v.39 no.3
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    • pp.451-459
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    • 2016
  • The development of radioprotector is being actively conducted in order to reduce the damage from over radiation exposure at radiation accident or radiation therapy. So this study was confirmed for radiation protective effects using the Cynanchi wilfordii Radix that has been known to be effective for antioxidant activity, anti-cancer, immune enhancing effects. The method of this study was administered orally Cynanchi wilfordii Radix ethanol extracts to Sprague Dawley Rat(SD Rat) for 14 days once a day, while measuring changed blood cell, spleen index, liver and uterus tissue along the change in time of 1, 4, 7 and 21 days after X-ray beam of 7 Gy irradiation. As the result of the experiment, the experimental group's rats which are administered with Cynanchi Wilfordii Radix ethanol extracts showed a rapid recovery in white blood cell count(p < 0.05) and spleen index(p < 0.05). In addition, condensation of nuclei, cytoplasmic swelling, and inflammatory cell infiltration in experimental group's liver cell was decreased more than in irradiation group's component. Further, experimental group's Uterine gland decreased the apoptosis more than irradiation group's components did. It is expected that Cynanchi Wilfordii Radix extracts will be useful as a new radioprotector. With above in mind, this paper may provide appropriate implications with the field of emergency management such as radiation accident.

Anti-tumor effects of Realgar on Stomach Cancer Cells (AGS), Glioma Cells (T98G, A172, SNU-489) and Prostate Cancer Cells (LNCaP) (석웅황의 시험관내 위암, 신경교종 및 전립선암 세포에 대한 항암 연구)

  • Kim, Seon-Ryang;Yoon, Seong-Woo;Ryu, Bong-Ha
    • The Journal of Internal Korean Medicine
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    • v.28 no.3
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    • pp.409-420
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    • 2007
  • Objectives : The purpose of this study was to identify the anti-tumor effects of realgar on various cancer cells through molecular biologic and cellular biologic methods. Materials & Methods : We used 5 kinds of cancer cell lines:stomach cancer cell (AGS), glioma cells (T98G, A172, SNU-489) and prostate cancer cells (LNCaP). We injected the boiled extract of realgar. $50{\mu}$g/ml and $100{\mu}$g/ml to culture media (ml) for 24 hours. We examined the morphological changes under an inverted microscope and a fluorescence microscope. We measured the suppressive effect on viability of 5 kinds of cancer cells via XTT assay. We examined the effect on the revelation of PARP cleavage, Bcl-2 protein and Bax protein by western blot analysis. Results : The extract of realgar caused markedly morphological changes on AGS, T98G, SNU-489, and LNCaP. All of them showed withdrawn and floating appearance. The suppressive effect on viability of AGS, T98G, A172, SNU-489, and LNCaP showed that each test group had more suppressive effect on viability of AGS, T98G, A172, SNU-489, and LNCaP than the control group, which was statistically significantly (p<0.01). The extract of realgar did not induce PARP cleavage in AGS, T98G, A 172, SNU-489, or LNCaP. In the revelation of protein related to apoptosis, the protein levels of Bcl-2 decreased and the protein levels of Bax increased in AGS, T98G, SNU-489, and LNCaP treated with realgar. The protein levels of Bcl-2 decreased and the protein levels of Bax did not change in A172 treated with realgar. Conclusions : This experiment showed that realgar has anti-tumor effect on stomach cancer cells (AGS), glioma cells (T98G, SNU-489L and prostate cancer cells (LNCaP)

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Anti-Oxidative and Neuroprotective Effects of Rhei Rhizoma on BV-2 Microglia Cells and Hippocampal Neurons (대황(大黃)의 항산화와 신경세포손상 보호효능에 대한 연구)

  • Myung, Sung-Ha;Kim, Youn-Sub
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.647-655
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    • 2005
  • This study demonstrated anti-oxidative and neuroprotective effects of Rhei Rhizoma. Anti-oxidative effects were studied on BV-2 microglia cells damaged by $H_2O_2$ and nitric oxide. Neuroprotective effects were studied by using oxygen/glucose deprivation of the organotypic hippocampal slice cultures. The results obtained are as follows; The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in CA1 region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The group treated with 50 mg/ml of Puerariae Radix demonstrated decreases of neuronal cell death area and cell death area percentages in CA1 region, but these were not significant statistically. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in dentate gyrus of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The group treated with 50 mg/ml of Puerariae Radix demonstrated decreases of neuronal cell death area and cell death area percentages in dentate gyrus, but these were not significant statistically. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of TUNEL-positive cells in both CA1 region and dentate gyrus of ischemic damaged hippocampus cultures. The group treated with 50 mg/ml of Puerariae Radix demonstrated significant decrease of TUNEL-positive cells in CA1 region, but not in dentate gyrus of ischemic damaged hippocampus. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant decreases of LDH concentrations in culture media of ischemic damaged hippocampus cultures. The group treated with 50 mg/ml of Puerariae Radix demonstrated decrease of LDH concentrations in culture media, but it was not significant statistically. The groups treated with 0.5 and 5 mg/ml of Puerariae Radix revealed significant increases of cell viabilities of BV-2 microglia cells damaged by $H_2O_2$. The group treated with 50 mg/ml of Puerariae Radix demonstrated increase of cell viability of BV-2 microglia cells, but it was not significant statistically. The group treated with 0.5 mg/ml of Puerariae Radix revealed significant increase of cell viability of BV-2 microglia cells damaged by nitric oxide. The groups treated with 5 and 50 mg/ml of Puerariae Radix demonstrated increases of cell viabilities of BV-2 microglia cells, but these were not significant statistically. These results suggested that Puerariae Radix revealed neuroprotective effects through the control effect of apoptosis and oxidative damages.

Phloroglucinol Inhibits the in vitro Differentiation Potential of CD34 Positive Cells into Endothelial Progenitor Cells

  • Kwon, Yi-Hong;Lee, Jun-Hee;Jung, Seok-Yun;Kim, Jae-Won;Lee, Sang-Hun;Lee, Dong-Hyung;Lee, Kyu-Sup;Lee, Boo-Yong;Kwon, Sang-Mo
    • Biomolecules & Therapeutics
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    • v.20 no.2
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    • pp.158-164
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    • 2012
  • Inhibiting the bioactivities of circulating endothelial progenitor cells (EPCs) results in significant inhibition of neovessel formation during tumor angiogenesis. To investigate the potential effect of phloroglucinol as an EPC inhibitor, we performed several in vitro functional assays using $CD34^+$ cells isolated from human umbilical cord blood (HUCB). Although a high treatment dose of phloroglucinol did not show any cell toxicity, it specifically induced the cell death of EPCs under serum free conditions through apoptosis. In the EPC colony-forming assay (EPC-CFA), we observed a significant decreased in the small EPC-CFUs for the phloroglucinol group, implying that phloroglucinol inhibited the early stage of EPC commitment. In addition, in the in vitro expansion assay using $CD34^+$ cells, treatment with phloroglucinol was shown to inhibit endothelial lineage commitment, as demonstrated by the decrease in endothelial surface markers of EPCs including $CD34^+$, $CD34^+/CD133^+$, $CD34^+/CD31^+$ and $CD34^+/CXCR4^+$. This is the first report to demonstrate that phloroglucinol can inhibit the functional bioactivities of EPCs, indicating that phloroglucinol may be used as an EPC inhibitor in the development of biosafe anti-tumor drugs that target tumor angiogenesis.

T-Type Calcium Channels Are Required to Maintain Viability of Neural Progenitor Cells

  • Kim, Ji-Woon;Oh, Hyun Ah;Lee, Sung Hoon;Kim, Ki Chan;Eun, Pyung Hwa;Ko, Mee Jung;Gonzales, Edson Luck T.;Seung, Hana;Kim, Seonmin;Bahn, Geon Ho;Shin, Chan Young
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.439-445
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    • 2018
  • T-type calcium channels are low voltage-activated calcium channels that evoke small and transient calcium currents. Recently, T-type calcium channels have been implicated in neurodevelopmental disorders such as autism spectrum disorder and neural tube defects. However, their function during embryonic development is largely unknown. Here, we investigated the function and expression of T-type calcium channels in embryonic neural progenitor cells (NPCs). First, we compared the expression of T-type calcium channel subtypes (CaV3.1, 3.2, and 3.3) in NPCs and differentiated neural cells (neurons and astrocytes). We detected all subtypes in neurons but not in astrocytes. In NPCs, CaV3.1 was the dominant subtype, whereas CaV3.2 was weakly expressed, and CaV3.3 was not detected. Next, we determined CaV3.1 expression levels in the cortex during early brain development. Expression levels of CaV3.1 in the embryonic period were transiently decreased during the perinatal period and increased at postnatal day 11. We then pharmacologically blocked T-type calcium channels to determine the effects in neuronal cells. The blockade of T-type calcium channels reduced cell viability, and induced apoptotic cell death in NPCs but not in differentiated astrocytes. Furthermore, blocking T-type calcium channels rapidly reduced AKT-phosphorylation (Ser473) and $GSK3{\beta}$-phosphorylation (Ser9). Our results suggest that T-type calcium channels play essential roles in maintaining NPC viability, and T-type calcium channel blockers are toxic to embryonic neural cells, and may potentially be responsible for neurodevelopmental disorders.

Enhanced Immune Activity and Cytotoxicity of Artemisia capillaris Thunb. Extracts against Human Cell Lines (사철쑥 추출물의 면역세포의 생육증진 및 세포독성)

  • Lee, Mi-Kyoung;Choi, Geun-Pyo;Ryu, Lee-Ha;Lee, Gang-Yoon;Yu, Chang-Yeon;Lee, Hyeon-Yong
    • Korean Journal of Medicinal Crop Science
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    • v.12 no.1
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    • pp.36-42
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    • 2004
  • The immune activation and anticancer activities of the water and ethanol extracts from Artemisia capillaris Thunb. were studied. The growth of human hepatocarcinoma and human gastric cancer cell was inhibited by the addition of $1.0\;mg/m{\ell}$ of the water extract, by about 77% and 95%, respectively. The growth of human breast cancer cells was also inhibited by addition of $0.5\;mg/m{\ell}$ of both water and ethanol extracts by 88%. The growth of human normal lung cell, HEL299 was inhibited by 15% indicating very low cytotoxicity of both extracts. Overall selectivity of the both extracts on several human cancer cell line was over 2.5. The growth of both human B and T cells was enhanced up to 1.6 to 2.1 times by adding the ethanol extracts. The secretion of cytokines, $TNF-{\alpha}$ and IL-6, from human B cells was also increased showing $68\;pg/m{\ell}$ and $67\;pg/m{\ell}$, respectively, compared to $35{\sim}40\;pg/m{\ell}$ of the control. In terms of the immune activity, there was not much difference between water and ethanol extracts of Artemisia capillaris Thunb. It implies that the extraction solvent could not differ the biological activities of the extracts. Based on these results, Artemisia capillaris Thunb. can be developed into a potentially useful cancer chemoprentive agent.