• Title/Summary/Keyword: taxol

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Effects of taxol and ionizing radiation on cytotoxicity and prostaglandin production in KB, RPMI-2650, SW-13 and L929 (수종과 암세포주와 섬유모세포주에서 taxol과 전리방사선이 세포독성과 prostaglandin생성에 미치는 영향)

  • Lee Keon-Il;You Dong-Soo
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.28 no.1
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    • pp.127-143
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    • 1998
  • The author evaluated the effects of taxol, a microtubular inhibitor, as a possible radiation sensitizer and the production of prostaglandins on three human cancer cell lines(KB, RPMI-2650 and SW-13) and one murine cell line(L929). Each cell line was divided into four groups (control, taxol only, radiation only and combination of taxol and radiation). The treatment consisted of a single irradiation of 10Gy and graded doses (5, 50, 100, 200, 300, 500 nM) of taxol for a 24-h period. The cytotoxicity of taxol alone was measured at 1 day after(1-day group) and 4 days after(4-day group) the treatment. The survival ratio of cell was analyzed by MTT (3-(4,5-dimethylthiazol-2-yl) -2,5-dimethyl tetrazolium bromide) test. Prostaglandins(PGE2 and PGI2) were measured in the culture medium by a radioimmunoassay. The results obtained were as follows. 1. There was a significantly increased cytotoxicity of KB cells in 4-day group than those in I-day group. There was a high correlation between doses of taxol and cell viability in both groups(l-day group R=0.82741, 4-day group R=0.84655). 2. There was a significantly increased cytotoxicity of RPMI -2650 cells treated with high concentration of taxol in 4-day group than those in I-day group. Also there was a high correlation between doses of taxol and cell viability in 4-day group(R=0.93917). 3. There was a significantly increased cytotoxicity of SW-13 cells treated with high concentration of taxol in 4-day group than those in 1-day group. However no high correlation was observed between doses of taxol and cell viability in both groups(1-day group R=0.46362, 4-day group R=0.65425). 4. There was a significantly increased cytotoxicity of L929 cells treated with low concentration of taxol in 4-day group than those in 1-day group. At the same time, there was a low correlation between doses of taxol and cell viability in both groups(1-day group R=0.34237, 4-day group R=0.23381). 5. In I-day group of L929 cells, higher cytotoxicities were observed in the groups treated with 500 nM taxol than given 10 Gy radiation alone. L929 cells in I-day group alone showed a radiosensitizing effect by taxol.. 6. In addition to L929 cells, all cancer cells treated with a combination of taxol and radiation in 4-day group appeared to have some fragmented nuclei and to float on the medium. In addition, L929 cells appeared to be more confluent. 7. The level of PGE2 production was the highest in the contol KB cells. This appeared to increase in every experimental group of all three cancer cells except L929 cells. There was a significantly increased production of PGE2 in SW -13 cells treated with a combination taxol and radiation compared to the other experimental groups. 8. The level of PGE2 production in the control group of RPMI-Z650 cells was the highest. This appeared to increase in every experimental group of all cells except in SW-13 cells. This also increased significantly in RPMI-2650 cells treated with a combination of taxol and radiation compared to the other experimental groups.

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

  • Kim, Kyu-Young;Lee, Jae-Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.5
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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.

Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

  • Wang, Ning-Ning;Zhao, Li-Jun;Wu, Li-Nan;He, Ming-Feng;Qu, Jun-Wei;Zhao, Yi-Bing;Zhao, Wan-Zhou;Li, Jie-Shou;Wang, Jin-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4983-4988
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    • 2013
  • Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

Analysis of Taxol and the Related Compound in Exotic Yew (Taxus Spp.) (외래주목의 Taxol 및 관련화합물의 분석)

  • Choi, Myung-Suk;Paik, Ki-Hyon;Kwak, Sang-Soo
    • Journal of the Korean Wood Science and Technology
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    • v.27 no.3
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    • pp.91-98
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    • 1999
  • The content of taxol and related compounds in needle and stem tissues of exotic yews growing in the Chollipo Arboretum which located in the West Sea of Korea were determined by HPLC. A considerable variation in contents of taxol and the related compounds within species and among cultivars were observed. The content of taxol was much higher in the needles than those in the young stem tissues except T. X media cv. Vermuleun, T. baccata cv. Washingtonii, and T. X cuspidata cv. Nana, and the content of 10-deacetyl baccatin III(10-DAB III) was also slightly higher in the needle. The needle of T. cuspidata cv. Nigra collected from April was contained the high amount of taxol(1,027 ${\mu}g$ per g dry weight) and also contained high quantity in 10-DAB III(267 ${\mu}g$ per g dry weight). Concentration of taxol in needle was significantly greater than those of meristemic and ovary tissues, Exotic yews growing at the Chollipo Arboretum containing T. cuspidata cv. Nigra could be suitable materials as a source for the tissue and cell cultures for production of taxol.

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Production, Purification, and Characterization of Taxol and 10-DABIII from a new Endophytic Fungus Gliocladium sp. Isolated from the Indian Yew Tree, Taxus baccata

  • Sreekanth, D.;Syed, A.;Sarkar, S.;Sarkar, D.;Santhakumari, B.;Ahmad, A.;Khan, M.I.
    • Journal of Microbiology and Biotechnology
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    • v.19 no.11
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    • pp.1342-1347
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    • 2009
  • We have isolated endophytic fungi from the Indian yew tree, Taxus baccata, and then screened for taxol production. Out of the 40 fungal cultures screened, one fungus Gliocladium sp. was found to produce taxol and 10-DABIII (10-deacetyl baccatin III). These compounds were purified by TLC and HPLC and characterized using UV-spectroscopy, ESI-MS, MS/MS, and proton NMR. One liter of Gliocladium sp. culture yielded $10\;{\mu}g$ of taxol and $65\;{\mu}g$ of 10-DABIII. The purified taxol from the fungus showed cytotoxicity towards cancer lines HL-60 (leukemia), A431 (epidermal carcinoma), and MCF-7 (breast cancer).

Inhibition of Nemo-like Kinase Increases Taxol Sensitivity in Laryngeal Cancer

  • Dong, Ji-Rui;Guo, Nan;Zhao, Jian-Pu;Liu, Pin-Duo;Feng, Hui-Hong;Li, Yan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.12
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    • pp.7137-7141
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    • 2013
  • Several studies have shown that nemo-like kinase (NLK) plays a vital role in apoptosis of cancer cells. The present research concerned effects and mechanisms of Taxol on NLK knockdown human laryngeal cancerHep-2 cell lines in vitro. Using RNAi, methyl-thiazoltetrazolium (MTT) assays, real-time RT-PCR, Western blotting and flow cytometry analysis, growth and the cell cycle progression of NLK knockdown Hep-2 cells and expression of downstream molecules were observed. Cell growth was obviously suppressed in the Taxol treated group (P<0.001, 48 hours). Cell numbers of combined Taxol-based chemotherapy with lentivirus mediated RNAi treatment group (Lv-shNLK+Taxol goup) were significantly different from NLK-specific siRNA lentivirus infected group (Lv-shNLK group) (p<0.001). Flow cytometry analysis revealed that Lv-shNLK+Taxol caused the G0/G1-phase DNA content to decrease from 44.1 to 3.33% (p<0.001) and the S-phase DNA content to increase from 38.4 to 82.0% (p<0.001), in comparison with the Lv-shNLK+Taxol group. Immunoblot analysis showed that knockdown of NLK led to significant reduction in the levels of cyclin D1, PCNA and PARP, whereas cyclin B1 was elevated in. Cell growth was also obviously suppressed in the Hep-2 cell line, knockdown of NLK making them more sensitive to Taxol treatment. NLK is expected to become a target of new laryngeal cancer gene therapies.

Analysis of Taxol and Cephalomannine in Cheju Island Yew (Taxus cuspidata S. et Z.) (제주도 주목(Taxus cuspidata S. et Z.)의 Taxol 및 Cephalomannine의 함량분석)

  • Kwak, Sang-Soo;Choi, Myung-Suk;Park, Young-Goo;Ko, Kyung-Soo;Liu, Jang-Ryol
    • Korean Journal of Pharmacognosy
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    • v.26 no.2
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    • pp.116-121
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    • 1995
  • To seek for a stable supply source of taxol as an anticancer agent urgently needed for the treatment of ovarian cancer, the concentrations of taxol and cephalomannine in bark and needles of 37 yew (Taxus cuspidata S. et Z.) trees grown in 6 locations of Cheju Island were analyzed by using HPLC. A considerable variation in the content was observed in plant part and the location. The average taxol content in the needles ($220.3{\;}{\pm}{\;}56{\;}{\mu}g$ per g dry wt) was ca. 4 times hgher than that in the bark, whereas the content of cephalomannine in the needles $(353{\;}{\pm}{\;}141{\;}{\mu}g)$ was ca. 5 times higher than that in the bark. Particularly, even within Cheju Island, needles from trees grown near the coast including Sogwipo area contained much higher taxol contents than needles from trees grown at mountain locations, indicating that taxane level is affected by environmental effects. Taxol in the needles was confirmed by electrospray mass spectrometry. These results suggest that the needles of yew trees growing in Cheju Island may provide a renewable source for taxol.

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Post-thawed Preimplantation Development and Production of Offsprings after Vitrification using Taxol $^{TM}$ a Cytoskeleton Stabilizer (마우스 성숙난자의 유리화 동결 중 Cytoskeleton Stabilizer, Taxol의 처리 후 배발달률과 산자의 생산)

  • 박성은;박이석;정형민
    • Journal of Embryo Transfer
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    • v.16 no.3
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    • pp.239-243
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    • 2001
  • Selection of oocyte cryopreservation method is a prerequisite factor for developing an effective bank system. Compared with slow freezing method, the vitrification has various advantages such as avoiding intracellular ice crustal formation. In our previous, we attempted to employ a vitrification method using ethylene glycol and an electron microscope grid for cryopreservation of mouse oocytes. However, A high incidence of spindle and chromosome abnormalities was detected in thawed oocytes after vitrification. We examined whether the addition of a cystoskeleton stabilizer Taxol $^{TM}$, to the vitrification solution could promote the post-thawed survival and subsequent development of stored oocytes. More oocytes developed to the 4-cell (44.7% vs. 69.7%), 8-cell (31.8% vs. 64.2%), morula (24.7% vs. 54.3%), and blastocyst (20.3% vs. 49.2%) stages after the addition of Taxol$^{TM}$ to the cryoprotectant than after no addition. 21 and 26 mouse pups were born after transfer of blastocyst derived from oocytes vitrified without and with Taxol. The addition of Taxol to vitrification solution greatly promoted post-thaw preimplantation development of ICR morose oocytes.tes.

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Sequential administration of camptothecin sensitizes human colon cancer HCT116 cells to paclitaxel via $p21^{Cip1/WAF1}$

  • Yoo, Jung-Min;Kim, Yun-Jin;Lee, Sung-Jae;Kim, Sang-Hoon
    • Animal cells and systems
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    • v.15 no.1
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    • pp.9-17
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    • 2011
  • Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

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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    • v.39 no.4
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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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