• Title/Summary/Keyword: Tubulin depolymerization

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Alyssin and Iberin in Cruciferous Vegetables Exert Anticancer Activity in HepG2 by Increasing Intracellular Reactive Oxygen Species and Tubulin Depolymerization

  • Pocasap, Piman;Weerapreeyakul, Natthida;Thumanu, Kanjana
    • Biomolecules & Therapeutics
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    • v.27 no.6
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    • pp.540-552
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    • 2019
  • To determine the chemopreventive potential of alyssin and iberin, the in vitro anticancer activities and molecular targets of isothiocyanates (ITCs) were measured and compared to sulforaphane in hepatocellular carcinoma cell HepG2. The SR-FTIR spectra observed a similar pattern vis-a-vis the biomolecular alteration amongst the ITCs-treated cells suggesting a similar mode of action. All of the ITCs in this study cause cancer cell death through both apoptosis and necrosis in concentration dependent manner ($20-80{\mu}M$). We found no interactions of any of the ITCs studied with DNA. Notwithstanding, all of the ITCs studied increased intracellular reactive oxygen species (ROS) and suppressed tubulin polymerization, which led to cell-cycle arrest in the S and $G_2/M$ phase. Alyssin possessed the most potent anticancer ability; possibly due to its ability to increase intracellular ROS rather than tubulin depolymerization. Nevertheless, the structural influence of alkyl chain length on anticancer capabilities of ITCs remains inconclusive. The results of this study indicate an optional, potent ITC (viz., alyssin) because of its underlying mechanisms against hepatic cancer. As a consequence, further selection and development of effective chemotherapeutic ITCs is recommended.

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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    • v.27 no.4
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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.

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.
    • Proceedings of the KSAR Conference
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    • 2004.06a
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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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Curative Resection of Inoperable, Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy with Taxotere and Cisplatin (절제 불가능한 국소 진행성 위암 환자에서 Taxotere 및 Cisplatin을 이용한 선행 화학 요법제의 투여 후 근치적 절제가 가능했던 2예)

  • Lee, Han-Hong;Hur, Hoon;Chae, Byung-Joo;Kim, Wook;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.5 no.1
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    • pp.57-64
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    • 2005
  • At diagnosis, the majority of patients with gastric cancer are found to have local invasion or distant organ metastasis, even though the sole measure for a complete cure is a curative resection. A curative resection is hardly applicable for those with invasion and metastasis; thus, trials with neoadjuvant chemotherapy for downstaging the cancer should be considered. Docetaxel is a semisynthetic taxane that promotes tubulin polymerization and inhibits microtubule depolymerization. In recent studies, many metastatic gastric cancers were treated using neoadjuvant chemotherapy with docetaxel, and the response rates were reported. We report here two cases of locally advanced, non-resectable gastric cancer that were candidates for a curative resection after induction chemotherapy with docetaxel and cisplatin.

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THE ANTICANCER EFFECT OF PACLITAXEL($Taxol^{(R)}$) IN ORAL SQUAMOUS CELL CARCINOMA XENOGRAFT (이종 이식된 구강편평세포 암종에서 Paclitaxel ($Taxol^{(R)}$)의 항암 효과)

  • Kim, Ki-Hwan;Kim, Chul-Hwan;Han, Se-Jin;Lee, Jae-Hoon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.28 no.2
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    • pp.95-110
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    • 2006
  • The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.