• 제목/요약/키워드: Microtubule depolymerization

검색결과 9건 처리시간 0.019초

Pertussis Toxin Inhibits Colchicine-Induced DNA Synthesis in Human Fibroblast

  • Jang, Won-Hee;Rhee, In-Ja
    • Archives of Pharmacal Research
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    • 제17권3호
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    • pp.199-203
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    • 1994
  • Several lines evidence indicate that microtubule depolymerization initiates DNA synthesis or enhances the effects of serum or purified growth factors in many types of fibroblasts. Yet little is known about the intracellular events responsible for the mitogenic effect of microtubule disrupting agents. The effects of antitubulin agents on DNA synthesis in sparse and dense cultures in the presence or absence of serum and possible involvement of G-proteins in their mitotic action were examined. In these studies, colchicine by itself appeared to be mitogenic only for confluent quiesecent human lung fibroblasts. In sparse culture, however, colchicine inhibited serum-stimulated DNA synthesis. Colcemid, another antitubulin agent, showed similar effects of growth inhibition and stimulation in sparse and confluent cultures while lumicolhicine, inactive colchicine, did not. The mitogenic effect of two antitubulin agents, colchicine and colcemid, was partially inhibited by pertussis toxin. These data suggest that microtubular integrity is associated with the expression of either negative or positive control on DNA synthesis and mitogenic effect of antitubulin agents may be partially mediated by pertussis toxin-sensitive G protein.

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The Effect of Taxol and Ethyl-N-phenylcarbamate (EPC) on Growth and Gravitropism in Zea mays L

  • Park, Yun-Hee;Choy, Yoon-Hi;Lee, June-Seung
    • Journal of Plant Biology
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    • 제39권4호
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    • pp.287-293
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    • 1996
  • The effect of taxol and ethyl-N-phenylcarbamate (EPC) on the growth and gravitropism of maize roots and coleoptiles was studied. Taxol is known to promote the assembly of microtubules (MTs) and stabilizes MTs by preventing depolymerization. EPC, on the contrary, is an anti-microtubule drug that promotes disassembly of MTs. Taxol, at 1 $\mu$M, inhibited gravitropic response of maize roots to about 40%, but did not inhibit growth; at 10 $\mu$M, it inhibited the gravitropic response of coleoptile segments of maize by approximately 50%, but did not inhibit growth, while 0.5 mM EPC inhibited both the gravitropic response and growth of maize roots by approximately 50%. Taxol, which inhibited the gravitropic response of maize roots and coleoptile segments, had no effect on either the polar or the bilateral transport of auxin. These results indicated that MT polymerization could not occur normally with taxol or EPC, so that if there was any abnormal rearrangement of MT, the gravitropic response was inhibited, which resulted from the inhibition of neither growth nor auxin transport. This results suggested that gravitropic response was related to the MT arrangement, and that both straight growth and the differential growth in gravitropic response could be regulated by different mechanisms.

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BRI3 associates with SCG10 and attenuates NGF-induced neurite outgrowth in PC12 cells

  • Gong, Yanhua;Wu, Jing;Qiang, Hua;Liu, Ben;Chi, Zhikai;Chen, Tao;Yin, Bin;Peng, Xiaozhong;Yuan, Jiangang
    • BMB Reports
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    • 제41권4호
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    • pp.287-293
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    • 2008
  • In a yeast two-hybrid screen, we identified the microtubule-destabilizing protein SCG10 as a potential effector protein of $BRI_3$. The association was verified using GST pull-down, Co-IP, and their perinuclear co-localization. The analysis of in vitro microtubule polymerization/depolymerization showed that the binding of $BRI_3$ to SCG10 effectively blocked the ability of SCG10 to induce microtubule disassembly, as determined by turbidimetric assays. In intact PC12 cells, $BRI_3$ exhibited the ability to stabilize the microtubule network and attenuate the microtubule-destabilizing activity of SCG10. Furthermore, co-expression of $BRI_3$ with SCG10 attenuated SCG10-mediated PC12 cell neurite outgrowth induced by NGF. These results identify a novel connection between a neuron-specific BRI protein and the cytoskeletal network, suggesting possible roles of BRI3 in the process of neuronal differentiation.

Effects of $Taxol^{TM}$ and Cytochalasin B on the Developmental Capacity of Vitrified Porcine Immature Oocytes

  • Kim, S. W;H. T. Cheong;B. K. Yang;Kim, C. I.;Park, C. K.
    • 한국동물번식학회:학술대회논문집
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    • 한국동물번식학회 2004년도 춘계학술발표대회
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    • pp.199-199
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    • 2004
  • This study was conducted to investigate cytoskeleton alterations during vitrified (Open Pulled Straw method) porcine immature oocytes, to utilize Taxol/sup TM/ (polymerization of tubulin molecules) and Cytochalasin B (CB, depolymerization of actin filaments) during vitrification to stabilize microtubule and microfilaments (MT and MF), and to determine in vitro maturation, fertilization and development of cytoskeletal-stabilized and vitrified porcine immature oocytes. (omitted)

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Microtubule Inhibitory Effects of Various SJ Compounds on Tissue Culture Cells

  • Lee Jong Han;Kang Dong Wook;Kwon Ho Suk;Lee Sun Hwan;Park Si Kyung;Chung Sun Gan;Chon Eui Hwan;Paik Soon Young;Lee Joo Hun
    • Archives of Pharmacal Research
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    • 제27권4호
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    • pp.436-441
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    • 2004
  • SJ compounds (SJ8002 and related compounds) are a group of novel anticancer agents (Cho, Chung, Lee, Kwon, Kang, Joo, and Oh. PCT/KR02/00392). To explore the anticancer mechanism of these compounds, we examined the effect of SJ8002 on microtubules of six human cell lines. At a high concentration ($2\;{\mu}g/mL$), SJ8002 effectively disrupted microtubules of the six cell lines within 1 h. At lower concentrations ($0.05\~1.0\;{\mu}g/mL$), the antimicrotubule activity of SJ8002 varied defending on cell lines. The inhibition of in vitro polymerization of pure tubulin by SJ8002 suggested that SJ8002 acts on free tubulin, inhibits the polymerization of tubulin dimer into microtubules, and hence induces the depolymerization of microtubules.

Paclitaxel에 의한 관절연골 세포의 capase-비의존적 mitotic catastrophe 유도 (Paclitaxel Induced Caspase-Independent Mitotic Catastrophe in Rabbit Articular Chondrocyte)

  • 임정희;김송자
    • 생명과학회지
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    • 제20권4호
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    • pp.519-527
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    • 2010
  • Paclitaxel은 미세소관의 탈중합을 억제하는 시약으로 알려져 있다. Paclitaxel은 다양한 세포에서 세포 내 방추체를 안정화시킴으로써 유사분열 억제 및 세포사멸을 유도한다. 본 실험에서는 토끼 관절 연골세포에서 paclitaxel이 연골세포의 증식과 사멸에 미치는 효과에 대한 연구를 수행하였다. MTT assay를 수행한 결과 paclitaxel은 연골세포에서 농도 의존적으로 세포 증식을 억제한다는 것을 확인 할 수 있었으며, FACS analysis와 Western blot analysis를 수행한 결과, paclitaxel이 G2/M 정지를 유도하는 것을 확인하였다. 또한, paclitaxel이 비정상적인 세포 분열유도와 핵 단편분절 유도없이 일어나는 mitotic catastrophe 즉, caspase-3 비의존적인 세포사멸을 유도하였다. Paclitaxel을 처리한 세포에서 일어나는 이러한 mitotic catastrophe에 의한 세포 죽음은 G1/S기의 진행을 억제하는 시약인 thymidine을 처리하는 것에 의해 억제되는 것을 확인할 수 있었다. 이러한 결과를 종합해 볼 때, paclitaxel에 의한 토끼 관절 연골 세포에서의 세포 죽음은 caspase-3 비의존적인 mitotic catastrophe에 의해 일어나는 것으로 사료되어진다.

Effects of Epothilone A in Combination with the Antidiabetic Drugs Metformin and Sitagliptin in HepG2 Human Hepatocellular Cancer Cells: Role of Transcriptional Factors NF-κB and p53

  • Rogalska, Aneta;Sliwinska, Agnieszka;Kasznicki, Jacek;Drzewoski, Jozef;Marczak, Agnieszka
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권3호
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    • pp.993-1001
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    • 2016
  • Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

절제 불가능한 국소 진행성 위암 환자에서 Taxotere 및 Cisplatin을 이용한 선행 화학 요법제의 투여 후 근치적 절제가 가능했던 2예 (Curative Resection of Inoperable, Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy with Taxotere and Cisplatin)

  • 이한홍;허훈;채병주;김욱;전해명
    • Journal of Gastric Cancer
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    • 제5권1호
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    • pp.57-64
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    • 2005
  • 위암의 치료에 있어서 근치적 절제는 완치를 위한 유일한 방법이나 불행이도 많은 환자들이 국소적이나 혹은 타 장기로 전이된 상태로 발견된다. 이런 경우에는 근치적 절제술의 시행이 매우 어렵고 선행 화학요법을 시행하여 병기를 낮추려는 시도가 고려되어야 한다. Docetaxel은 반합성 택산으로 튜불린의 중합 반응을 유도하고 미세관의 해중합 반을을 방해함으로서 그 작용을 나타낸다. 현재 전이성 위암의 신행화학요법에서 docetaxel의 사용이 많이 시도되고 있고 그 반응률이 보고되고 있다. 본 교실에서는 docetsxel과 cisplatin 병용요법을 시행하여 전이성 위암의 부분 관해로 근치적 절제가 가응하였던 2예를 보고하는 바이다.

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구강 편평세포암종 세포주에서 Cyclosporin A와 Taxol 투여시 PI-3 kinase/Akt1 Pathway에 의한 세포사멸 병용효과 (APOPTOTIC EFFECT IN COMBINATION OF CYCLOSPORIN A AND TAXOL ON ORAL SQUAMOUS CELL CARCINOMA CELL LINE THROUGH THE PI-3 KINASE/AKT1 PATHWAY)

  • 김규영;이재훈
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • 제33권5호
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    • pp.426-436
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    • 2007
  • Oral cancer take up 2-6% of all carcinomas and squamous cell carcinoma, which is the most common type in oral cancer, has a poor prognosis due to its high metastasis and recurrence rates. In treating oral cancer, chemotherapy to the primary, metastasized and recurrent lesion is a very important and useful treatment, even though its widespread usage is limited due to high general toxicity and local toxicity to other organs. Taxol, a microtubule stabilizing agent, is an anticancer drug that induces cell apoptosis by inhibiting depolymerization of microtubules in between the metaphase and anaphase of the cell mitosis. Recently, its effectiveness and mechanism on various tumor has been reported. However, not much research has been done on the application of Taxol to oral squamous cell carcinoma. Cyclosporin A, which is an immunosuppressant, is being used on cancers and when co-administered with Taxol, effectiveness of Taxol is enhanced by inhibition of Taxol induced multidrug resistance. In this study, Cyclosporin A with different concentration of Taxol was co-administered to HN22, the oral squamous cell carcinomacell line. To observe the cell apoptosis and the mechanisms that take part in this process, mortality evaluation of tumor cell using wortmannin, c-DNA microarray, RT-PCR analysis, cytometry analysis and western blotting were used, and based upon the observation on the effect and mechanism of the agent, the following results were obtained: 1. The HN22 cell line viability was lowest when $100{\mu}M$ of Wortmannin and $5{\mu}g/ml$ of Taxol were co-administered, showing that Taxol participates in P13K-AKT1 pathway. 2. In c-DNA microarray, where $1{\mu}g/ml$ of cyclosporine A and 3mg/ml of Taxol were co-administered, no up regulation of AKT1, PTEN and BAD c-DNA that participate in cell apoptosis was observed. 3. When $1{\mu}g/ml$ of Cyclosporin A was applied alone to HN22 cell line, no difference was found in AKT1, PTEN and BAD mRNA expression. 4. Increased AKT1, mRNA expression was observed when $3{\mu}g/ml$ of Taxol was applied alone to HN22 cell line. 5. When $1{\mu}g/ml$ of Cyclosporin A and Taxol($3{\mu}g/ml\;and\;5{\mu}g/ml$) were co-administered to HN22 cell line, PTEN mRNA expression increased, whereas AKT1 and BAD mRNA decreased. 6. As a result of cytometry analysis, in the group of Cyclosporin A($1{\mu}g/ml$) and Taxol($3{\mu}g/ml$) co-administration, increased Annxin V was observed, which shows that apoptosis occurred by deformation of plasma membrane. However, no significant difference was observed with vary ing concentration. 7. In western blot analysis, no caspase 3 was observed in the group of Cyclosporin A($1{\mu}g/ml$) and Taxol($3{\mu}g/ml$) co-administration. From the results of this study, it can be concluded that synergistic effect can be observed in combination therapy of Taxol and Cyclosporin A on oral squamous cell carcinoma cell line, where decreased activity of the cell line was observed. This resulted in decreased AKT1 and BAD mRNA and increased PTEN mRNA expression and when wortmannin and Taxol were co-administered, the viability decreased which confirms that Taxol decreases the viability of tumor cell line. Hence, when Taxol and cyclosporine A are co-administered, it can be assumed that cell apoptosis occurs through AKt1 pathway.