• 제목/요약/키워드: p53 activation

검색결과 321건 처리시간 0.027초

Potentiation of Apoptin-Induced Apoptosis by Cecropin B-Like Antibacterial Peptide ABPs1 in Human HeLa Cervical Cancer Cell Lines is Associated with Membrane Pore Formation and Caspase-3 Activation

  • Birame, Basse Mame;Wang, Jigui;Yu, Fuxian;Sun, Jiazeng;Li, Zhili;Liu, Weiquan
    • Journal of Microbiology and Biotechnology
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    • 제24권6호
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    • pp.756-764
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    • 2014
  • Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in chicken or human tumor cells, localizing in their nuclei as opposed to the cytoplasm of non-transformed cells. The present study was undertaken to investigate whether ABPs1 could potentiate apoptin-induced apoptosis in HeLa cells. ABPs1 and the apoptin genes were successfully cloned into pIRES2-EGFP expression vector and expressed in HeLa cells. We report that ABPs1 augments apoptin cell growth inhibition in a concentration- and time-dependent manner. The DAPI staining and scanning electron microscopy observations revealed apoptotic bodies and plasma membrane pores, which were attributed to apoptin and ABPs1, respectively. Further, ABPs1 in combination with apoptin was found to increase the expression of Bax and to decrease the expression of survivin compared with either agent alone or the control. The apoptotic rate of HeLa cells treated with ABPs1 and apoptin in combination for 48 h was 53.95%. The two-gene combination increased the caspase-3 activity of HeLa cells. Taken together, our study suggests that ABPs1 combined with apoptin significantly inhibits HeLa cell proliferation, and induces cell apoptosis through membrane defects, up-regulation of Bax expression, down-regulation of survivin expression, and activation of the caspase-3 pathway. Thus, the combination of ABPs1 and apoptin could serve as a means to develop novel gene therapeutic agents against human cervical cancer.

HY251, a Novel Decahydrocyclopenta[a]indene Analog, Induces Apoptosis via tBid-Mediated Intrinsic Pathway in Human Ovarian Cancer PA-1 Cells

  • Suh, Hyewon;Choi, Ko-Woon;Kim, Myung Sic;Kim, Jeong Hyeon;Noh, Sun Young;Sung, Moon-Hee;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • 제22권11호
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    • pp.1591-1595
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    • 2012
  • We previously isolated a novel compound, HY251, with the molecular structure of 3-propyl-2-vinyl-1,2,3,3a,3b,6,7,7a,8,8a-decahydrocyclopenta[a]indene-3,3a,7a,8a-tetraol from the roots of Aralia continentalis. The current study was designed to evaluate the detailed molecular mechanisms underlying the apoptotic induction by HY251 in human ovarian cancer PA-1 cells. TUNEL assay and Western blot analyses revealed an appreciable apoptotic induction in PA-1 cells treated with $60{\mu}M$ of HY251 for 24 h. This apoptotic induction was associated with caspase-8-dependent Bid cleavage, which in turn resulted in the formation of pro-apoptotic truncated Bid (tBid), and activation of caspase-9 and -3, as well as the cleavage of poly(ADP-ribose) polymerase (PARP). Moreover, we found that this death event was also associated with the significant up-regulation and activation of the p53 tumor-suppressor protein through phosphorylation at Ser15. Therefore, we suggest that HY251 may be a potent cancer chemotherapeutic candidate for the treatment of ovarian cancer.

Magnetic biochar from alkali-activated rice straw for removal of rhodamine B from aqueous solution

  • Ren, Zhaogang;Chen, Fang;Wang, Bin;Song, Zhongxian;Zhou, Ziyu;Ren, Dong
    • Environmental Engineering Research
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    • 제25권4호
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    • pp.536-544
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    • 2020
  • To address organic dye wastewater, economic and effective adsorbents are required. Here, magnetic biochar from alkali-activated rice straw (AMBC) was successfully synthesized using one-step magnetization and carbonization method. The alkaline activation caused the large specific surface area, high pore volume and abundant oxygen-containing groups of the AMBC, and the magnetization gave the AMBC a certain degree of electropositivity and fast equilibrium characteristics. These characteristics collectively contributed to a relative high adsorption capacity of 53.66 mg g-1 for this adsorbent towards rhodamine B (RhB). In brief, RhB can spontaneously adsorb onto the heterogeneous surface of the AMBC and reach the equilibrium in 60 min. Although the initial pH, ionic strength and other substances of the solution affected the adsorption performance of the AMBC, it could be easily regenerated and reused with considerable adsorption content. Based on the results, H-bonds, π-π stacking and electrostatic interactions were speculated as the primary mechanisms for RhB adsorption onto the AMBC, which was also demonstrated by the FTIR analysis. With the advantageous features of low cost, easy separation, considerable adsorption capacity and favorable stability and reusability, the AMBC would be a potential adsorbent for removing organic dyes from wastewater.

Cell Survival, Apoptosis and AMPK-COX-2 Signaling Pathway of Mammary Tumor Cells after Genistein Treatment Combined with Estrogen

  • Lee, Yun-Kyoung;Hwang, Jin-Taek;Kim, Young-Min;Park, Ock-Jin
    • Preventive Nutrition and Food Science
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    • 제12권4호
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    • pp.197-201
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    • 2007
  • Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.

Oncogenic Activation of Fibroblast Growth Factor Receptor-3 and RAS Genes as Non-Overlapping Mutual Exclusive Events in Urinary Bladder Cancer

  • Pandith, Arshad A;Hussain, Aashaq;Khan, Mosin S;Shah, Zafar A;Wani, M Saleem;Siddiqi, Mushtaq A
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권6호
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    • pp.2787-2793
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    • 2016
  • Background: Urinary bladder cancer is a common malignancy in the West and ranks as the $7^{th}$ most common cancer in our region of Kashmir, India. FGFR3 mutations are frequent in superficial urothelial carcinoma (UC) differing from the RAS gene mutational pattern. The aim of this study was to analyze the frequency and association of FGFR3 and RAS gene mutations in UC cases. Materials and Methods: Paired tumor and adjacent normal tissue specimens of 65 consecutive UC patients were examined. DNA preparations were evaluated for the occurrence of FGFR3 and RAS gene mutations by PCR-SCCP and DNA sequencing. Results: Somatic point mutations of FGFR3 were identified in 32.3% (21 of 65). The pattern and distribution were significantly associated with low grade/stage (p<0.05). The overall mutations in exon 1 and 2 in all the forms of RAS genes aggregated to 21.5% and showed no association with any clinic-pathological parameters. In total, 53.8% (35 of 65) of the tumors studied had mutations in either a RAS or FGFR3 gene, but these were totally mutually exclusive in and none of the samples showed both the mutational events in mutually exclusive RAS and FGFR3. Conclusions: We conclude that RAS and FGFR3 mutations in UC are mutually exclusive and non-overlapping events which reflect activation of oncogenic pathways through different elements.

Arctigenin induces caspase-dependent apoptosis in FaDu human pharyngeal carcinoma cells

  • Kang, Kyeong-Rok;Kim, Jae-Sung;Lim, HyangI;Seo, Jeong-Yeon;Park, Jong-Hyun;Chun, Hong Sung;Yu, Sun-Kyoung;Kim, Heung-Joong;Kim, Chun Sung;Kim, Do Kyung
    • The Korean Journal of Physiology and Pharmacology
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    • 제26권6호
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    • pp.447-456
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    • 2022
  • The present study was carried out to investigate the effect of Arctigenin on cell growth and the mechanism of cell death elicited by Arctigenin were examined in FaDu human pharyngeal carcinoma cells. To determine the apoptotic activity of Arctigenin in FaDu human pharyngeal carcinoma cells, cell viability assay, DAPI staining, caspase activation analysis, and immunoblotting were performed. Arctigenin inhibited the growth of cells in a dose-dependent manner and induced nuclear condensation and fragmentation. Arctigenin-treated cells showed caspase-3/7 activation and increased apoptosis versus control cells. FasL, a death ligand associated with extrinsic apoptotic signaling pathways, was up-regulated by Arctigenin treatment. Moreover, caspase-8, a part of the extrinsic apoptotic pathway, was activated by Arctigenin treatments. Expressions of anti-apoptotic factors such as Bcl-2 and Bcl-xL, components of the mitochondria-dependent intrinsic apoptosis pathway, significantly decreased following Arctigenin treatment. The expressions of pro-apoptotic factors such as BAX, BAD and caspase-9, and tumor suppressor -53 increased by Arctigenin treatments. In addition, Arctigenin activated caspase-3 and poly (ADP-ribose) polymerase (PARP) induced cell death. Arctigenin also inhibited the proliferation of FaDu cells by the suppression of p38, NF-κB, and Akt signaling pathways. These results suggest that Arctigenin may inhibit cell proliferation and induce apoptotic cell death in FaDu human pharyngeal carcinoma cells through both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway.

전기자극 후 Cycloheximide 처리가 돼지난자의 활성화에 미치는 효과 (Effects of Cycloheximide on Development of In Vitro Matured Porcine Oocytes Activated following Eelectric Pulse)

  • 송상현;정기화;조헌조;박충생
    • 한국가축번식학회지
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    • 제26권1호
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    • pp.79-85
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    • 2002
  • 본 연구에서는 전기자극 후 cycloheximide의 적정농도와 배양시간이 체외성숙된 돼지난자의 활성화에 미치는 영향을 조사하고자 실험을 수행하였다. 42~44시간 동안 체외성숙 된 난자는 0.1%의 hyaluronidase에서 pipetting으로 난구세포를 제거한 후, 1.2 KV/cm의 전압으로 전기자극만 하거나, 전기자극 후 cycloheximide 1, 5 및 10 $\mu\textrm{g}$/$m\ell$의 농도에서 각각 3, 5 및 7시간 동안 배양하는 구로 나누어 활성화를 유도하여 다음과 같은 결과를 얻었다. 1. 난자의 분할율 cycloheximide 10 $\mu\textrm{g}$/$m\ell$ 처리군이 86.8%로 1 $\mu\textrm{g}$/$m\ell$ 처리군의 74.4%보다 유의적(P<0.05)으로 높았다. 배반포기 발달율은 10 $\mu\textrm{g}$/$m\ell$ 처리구보다 5 $\mu\textrm{g}$/$m\ell$ 처리구에서 유의적(P<0.05)으로 높았다. 2. 전기자극 후 cycloheximide에서 배양시간의 비교에 있어서 5시간 처리한 돼지난자의 분할율(86.6%)이 3시간 동안 처리한 난자보다 유의적(P<0.05)으로 높게 나타났다. 상실배의 발달율은 5시간과 7시간 동안 처리구(26.7%와 16.4%)에서 3시간 처리구(14.5%)보다 유의적(P<0.05)으로 높은 발달율을 나타났다. 3. 전기자극을 단독처리하거나 전기 자극 후 cyclohiximide를 복합처리한 돼지난자를 8일 동안 배양하였다. 전기자극 후 cycioheximide를 복합처리한 난자의 분할율(80.1%) 및 배반포기 발달율(11.6%)은 전기자극 단독처리한 난자의 분할율(77.2%) 및 배반포기 발달율(6.6%)과는 유의적인 차이가 없었다. 4. 체외성숙된 돼지난자를 전기자극 단독 또는 전기자극 후 cycloheximide 복합처리한 후 체외 발달한 배반포기 수정란의 핵 수는 각각 18.67$\pm$5.53개와 20.71$\pm$6.16개로써 유의적인 차이가 없었다. 이상의 결과를 요약하면, 전기자극을 단독처리 하거나 전기 자극 후 cyclohiximide를 복합처리한 돼지난자 발생율은 유의적인 차이가 없었으나, 전기자극 후 cycloheximide를 복합처리 할 경우에는 5 $\mu\textrm{g}$/$m\ell$의 농도로 5시간 동안 배양하는 것이 효과적으로 돼지난자의 activation을 유기할 수 있을 것으로 사료된다.

자금정(紫金錠)이 간암세포주 HepG2의 세포고사 및 세포주기에 미치는 영향 (Induction of Apoptosis and Cell Cycle Arrest by Jageum-Jung in HepG2 Hepatoma Cells)

  • 조영기;전지영;신용진;설재균;이재화;원진희;문구
    • 대한한방내과학회지
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    • 제28권4호
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    • pp.694-708
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    • 2007
  • Objectives : Jageum-Jung is used as an anti-cancer agent in oriental medicine, but the mechanism by which it induces cell death in cancer cells is still unclear. The purpose of this study was to investigate the effects of Jageum-Jung on apoptosis and cell cycle arrest in HepG2 hepatoma cells. Methods : Various cancer cell lines including HepG2, C6 glioma, SH-SY5Y, PANC-1, and MCF-7 cells, were used. Apoptosis was determined by DAPI nuclei staining and flow cytometry in HepG2 cells treated with various concentrations (from 25 to 200 ${\mu}g/ml$) of $H_2O$ extract of Jageum-Jung (JGJ) for 48 hrs. Expression of cell cycle arrest mediators including Rb, p53, p21, cyclin B1, cdk4, and cyclin E proteins were measured by Western blot analysis. To estimate intracellular hydrogen peroxide levels and intracellular nitric oxide levels, HepG2 cells were stained with DCFH-DA dye and DAF dye, subjected on flow cytometric analysis. Results : 1. Jageum-Jung decreased the viability of HepG2 cells in a dose-dependent manner. 2. Jageum-Jung induced the catalytic activation of caspase-3 in HepG2 cells. 3. Jageum-Jung increased the intracellular hydrogen peroxide and NO in HepG2 cells. 4. Jageum-Jung increased the expression of Rb, p53 and p21 in HepG2 cells. 5. Jageum-Jung induced the expression of cyclin B1, cdk4, and cyclin E in HepG2 cells. Conclusions : Taken together, we suggest that Jageum-Jung exhibits cytotoxic effects on HepG2 cells, causing apoptosis and cell cycle arrest. The results showed that Jageum-Jung may do so by regulating the expression of specific target molecules that promote efficient apoptotic cell death following $G_2$/M phase arrest in a dose-dependent manner.

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맥동 전자기장 처리에 의한 독소루비신 유도 유방암 세포 생존저하 촉진 (Pulsed Electromagnetic Field Enhances Doxorubicin-induced Reduction in the Viability of MCF-7 Breast Cancer Cells)

  • 우성훈;김윤석
    • 대한임상검사과학회지
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    • 제56권1호
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    • pp.73-84
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    • 2024
  • 펄스 전자기장(pulsed electromagnetic field, PEMF)은 여러 항암제의 항암 효과를 향상시키는 것으로 알려져 있고 독소루비신(doxorubicin, DOX)은 유방암을 포함한 다양한 종류의 악성 종양을 치료하는 데 사용되는 항암제이다. 본 연구는 PEMF가 MCF-7 유방암 세포에 대한 DOX의 항암 효과 증진 여부를 조사하고 관련기전을 규명하기 위해 진행되었다. 본 연구팀은 DOX와 PEMF를 동시에 처리하면 DOX 단독 처리에 비해 MCF-7 유방암 세포의 생존율 감소가 더 커지는 것을 확인하였다. PEMF는 cyclin-dependent kinase 2의 인산화와 p53, p21, 사이클린 E2 및 polo like kinase 1의 단백질 발현에 영향을 주어 DOX 처리에 의한 G1 세포주기 정지를 더욱 증가시켰다. 또한, PEMF는 DOX 처리에 의한 Fas와 Bcl-2-associated X의 증가, myeloid leukemia 1과 survivin의 감소, 카스파제(caspase)-8/9/7의 활성 및 poly (adenosine diphosphate-ribose) polymerase 절단을 더욱 증가시켰다. 이러한 연구결과를 바탕으로, 본 연구팀은 PEMF는 DOX 처리에 의한 G1 세포주기 정지와 카스파제 의존적 세포자멸사를 더욱 증가시켜 DOX 처리에 의한 MCF-7 세포의 생존율 감소를 더욱 증진시킴을 확인할 수 있었다.

The Use of Oyster Shell Powders for Water Quality Improvement of Lakes by Algal Blooms Removal

  • Huh, Jae-Hoon;Choi, Young-Hoon;Lee, Hyun-Jae;Choi, Woo Jeong;Ramakrishna, Chilakala;Lee, Hyoung-Woo;Lee, Shin-Haeng;Ahn, Ji-Whan
    • 한국세라믹학회지
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    • 제53권1호
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    • pp.1-6
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    • 2016
  • In this year, Koreans have a shortage in agricultural and drinking water due to severe algal blooms generated in major lakes. Waste oyster shells were obtained from temporary storage near the workplace at which oysters were separated from their shells. Heating ($1000^{\circ}C$ for 1 h in air) was employed to convert raw oyster shell powders into calcium oxide powders that reacted efficiently with phosphorus and nitrogen to remove algal blooms from eutrophicated wastewater. As the dispersed amount of heated oyster shell powders was increased, water clarity and visual light penetration were improved. Coagulation, precipitation and carbonation process of the heated oyster shell powders in a water purifier facilitated removal of eutrophication nutrient such as phosphorus and nitrogen, which is both beneficial and economically viable. $CO_2$ implantation by carbonation treatment not only produced thermodynamically stable CaO in oyster shells to derive precipitated calcium carbonate (PCC) but also accelerated algal removal by activation of coagulation and precipitation process. The use of oyster shell powders led to a mean reduction of 97% in total phosphate (T-P), a mean reduction of 91% in total nitrogen (T-N) and a maximum reduction of 51% in chemical oxygen demand (COD), compared with the total pollutant load of raw algal solution. Remarkable water quality improvement of algal removal by heated oyster shell powders and PCC carbonation treatment will allow utilization as water resources to agricultural or industrial use.