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  • American Association for Cancer Research (AACR)  (14)
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  • American Association for Cancer Research (AACR)  (14)
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  • 1
    Online Resource
    Online Resource
    Gabexate Mesilate Inhibits Colon Cancer Growth, Invasion, and Metastasis by Reducing Matrix Metalloproteinases and Angiogenesis
    American Association for Cancer Research (AACR) ; 2004
    In:  Clinical Cancer Research Vol. 10, No. 13 ( 2004-07-01), p. 4517-4526
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 10, No. 13 ( 2004-07-01), p. 4517-4526
    Abstract: Gabexate mesilate (GM), a synthetic protease inhibitor, has an antiproteinase activity on various types of plasma serine proteases. However, its role on matrix metalloproteinases (MMPs) has not been identified. In this study, we investigated the effect of GM on MMPs and on the invasion and metastasis of human colon cancer cell lines and neoangiogenesis. The activities of MMPs secreted from these cells were significantly reduced by GM but unaffected by the serine protease inhibitor aprotinin. GM directly inhibited purified progelatinase A derived from T98G human glioblastoma cells. In vitro, GM significantly reduced the invasive ability of colon cancer cells but not cellular motility, whereas aprotinin affected neither. Liver metastatic ability and tumorigenic potential in nude mice were remarkably reduced on treatment with GM. Immunohistochemical analysis of GM-treated tumors in mice showed a marked increase in apoptosis and a significant reduction in tumor angiogenesis. Human umbilical vein endothelial cell proliferation, tube formation, and neoangiogenesis in the rabbit cornea and Matrigel implanted in mice were significantly inhibited by GM. These results suggest that GM is a novel inhibitor of MMPs and that it may inhibit the invasion and metastasis of human colon cancer cells by blocking MMPs and neoangiogenesis.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-04-0084
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2004
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 2
    Online Resource
    Online Resource
    Abstract 4457: Omega-3 polyunsaturated fatty acids induce apoptosis cell death and inhibit LPS-induced invasion in PC3 cells
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4457-4457
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4457-4457
    Abstract: Dietary fat as a potential risk factor for cancer has been the focus of many epidemiologic and basic researchers, but the findings have been inconclusive. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we have investigated anticancer action of ω3-PUFAs and effect of ω3-PUFAs on LPS-mediated TLR4 signaling in prostate cancer. DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) treatment resulted in a dose-dependent reduction of cell viability with apoptosis of PC3 cells as confirmed by TUNEL assay. In contrast, AA (arachidonic acid), a ω6-PUFA, exhibited no significant effect. Moreover, invasiveness of PC3 cells was inhibited in a dose-dependent manner by treatment of DHA, while AA showed no significant effect. In zymography, MMP-2 activity was inhibited by DHA treatment and MMP-9 and MMP-2 promoter activities were also inhibited. DHA inhibited Cox-2 and VEGF promoter activities and NF-kB reporter activity was also decreased. The expression of TLR4 was confirmed by RT-PCR in PC3 cells and DHA dramatically inhibited the LPS-induced invasion of PC3 cells. In in vivo experiments, when mouse prostate cancer cells (RM1) were injected into the tail vein of Fat1 mice (Fat1 transgenic mice express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously.) and WT (wild type mice), lung metastasis was significantly inhibited in Fat1 transgenic mice compared to WT mice. In conclusion, the present study suggests that ω3-PUFAs may inhibit prostate cancer cell growth, and invasion through decrease of MMPs, Cox-2, VEGF and NF-kB reporter activities. Moreover LPS-mediated invasiveness was inhibited by DHA. These findings provide important preclinical evidence and molecular insight for utilization of ω-3 PUFAs for the chemoprevention and treatment of human prostate cancer. [This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4457.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-4457
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    Abstract 1340: High densities of tumor-infiltrating FOXP3+ regulatory T cells in primary tumor or lymph node metastasis are associated with favorable outcome in gastric cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1340-1340
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1340-1340
    Abstract: Background: It has been reported that the frequency of FOXP3+ regulatory T cells (Tregs) among tumor-infiltrating lymphocytes is increased in cancer-bearing patients. We designed the study to determine the prognostic significance of FOXP3+ Tregs in gastric cancer. Methods: Tissue microarray and immunohistochemistry were used to assess the densities of FOXP3+ T regs in primary tumor tissue (n=216) and unmatched metastatic tumor tissue of regional lymph nodes (n=149) from gastric cancer patients. Numbers of FOXP3+ Tregs were counted using an image analysis program. FOXP3+ Treg densities were evaluated for correlation with clinicopathologic characteristics and overall survival. Results: With respect to primary tumor, low density of FOXP3+ Tregs was associated with advanced T stage (p = 0.028), but not with any other clinicopathologic features. Kaplan-Meier survival analysis revealed that the high density group of FOXP3+ Tregs had longer survival time than the low density group (p = 0.001, log-rank test). In multivariate analysis, FOXP3+ Treg density remained an independent prognostic factor with hazard ratio (95% CI) of 0.651 (0.435-0.975). In addition, it was found that FOXP3+ Treg density in metastatic tumor of lymph nodes was an independent prognostic indicator, i.e., high density of FOXP3+ Tregs was significantly associated with improved survival (hazard ratio (95% CI) = 0.519 (0.318-0.848)). Conclusions: FOXP3+ Treg densities in not only primary tumor, but also metastatic loci of regional lymph nodes were significantly associated with patient survival in gastric cancer. As our finding that high density of FOXP3+ Tregs was related to favorable prognosis contrasts with several previous studies, further investigation will be needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1340.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-1340
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    Online Resource
    Online Resource
    Abstract 4439: Anti-cancer actions of omega-3 polyunsaturated fatty acids in human cervical cancer
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4439-4439
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4439-4439
    Abstract: Over 90% of human cervical carcinoma is associated with high risk human papillomavirus (HPV), and a number of biological effects that could contribute to cancer suppression by ω3-polyunsaturated fatty acids (ω3-PUFAs) have been reported. However, the anti-cancer effect of ω3-PUFAs on cervical cancer has been not known yet. In this study, we report inhibitory mechanisms of ω3-PUFAs on cell growth and invasion in cervical cancer. DHA inhibited the cell growth in a dose- and time-dependent manner. In flow cytometry analysis, cell cycle of DHA-treated HeLa cells was arrested in G2/M phase and SubG1 cells also increased. Moreover, apoptotic cell death was confirmed by TUNEL assay, the induction of PARP cleavage and down-regulation of Bcl-2. The invasiveness of cells was significantly inhibited by DHA treatment in vitro transwell assay as well. The MMP-9 and MMP-2 promoter activities were decreased after DHA treatment. Cox-2 and VEGF promoter activities were also inhibited by DHA. Furthermore, DHA decreased the levels of reporter activity of NF-κB, which is transcription factor that regulates MMPs, Cox-2 and VEGF expression. In in vivo experiments, when human papillomavirus type 16 (HPV16)-transformed mouse TC-1 cells were injected into the tail vein of Fat1 mice (Fat1 transgenic mice express a Caenorhabditis elegans ω3-desaturase converting ω6- to ω3-PUFAs endogenously.) and WT (wild type) mice, lung metastasis of TC-1 cells was dramatically inhibited in Fat1 transgenic mice compared to WT mice. Taken together, these findings provide evidence that ω3-PUFAs may inhibit metastasis as well as cell growth and invasion through suppression of MMPs/COX-2/VEGF expression by inhibition of NF-κB expression in cervical cancer cells, indicating that the utilization of ω3-PUFAs may represent a potential effective therapy for the chemoprevention and treatment of human cervical cancer.[This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government(MEST) (#E00026) and by the Infection Signaling Network Research Center (R13-2007-020-01000-0) at Chungnam National University] . Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4439.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-4439
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 5
    Online Resource
    Online Resource
    Abstract 2867: Docosahexaenoic acid induces autophagy through p53/AMPK/mTOR signaling in human cancer cells
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2867-2867
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2867-2867
    Abstract: Although Omega 3-polyunsatuarated fatty acids (Omega 3-PUFAs) induce cytotoxicity in several cancer cell lines, the exact mechanisms are not identified yet. In this study, we showed that autophagy is involved in the Omega 3-PUFAs-induced cytotoxicity in cancer cells. Autophagy is characterized by the sequestration of cytoplasmic material within autophagosomes for bulk degradation by lysosomes. We found that docosahexaenoic acid (DHA), an Omega 3-PUFA, induced not only apoptosis but also autophagy in cancer cells. Autophagy was detected after DHA exposure as indicated by induction of LC3 expression, and formation of autophagic vacuolization. We observed that the DHA-induced autophagy was accompanied by loss of p53. Inhibition of p53 by Pifithrin-α or microRNA-p53 significantly increased the DHA-induced autophagy, suggesting that the DHA-induced autophagy is mediated by downregulation of p53. Further experiments showed that the mechanism of the DHA-induced autophagy associated with p53 attenuation, involved an increase in the active form of AMPK which attenuated the mTOR activity as revealed by p27 sequestration. In addition, compelling evidence for the interplay between autophagy and apoptotic cell death induced by DHA is supported by the findings that autophagy inhibition partially decreased the DHA-induced apoptotic cell death and further autophagy induction by p53 inhibitor enhanced apoptosis in response to treatment with DHA in cancer cells. Our results demonstrate that autophagy may be related to the DHA-induced cytotoxicity in cancer cells. [This work was supported by basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (E00026 and R13-2007-020-01000-0]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2867. doi:10.1158/1538-7445.AM2011-2867
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-2867
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 6
    Online Resource
    Online Resource
    Abstract 5646: Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion and angiogenesis of SW480 human colon cancer cells by modulating Wnt/b-catenin signaling
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Research Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5646-5646
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 5646-5646
    Abstract: It is known that polysaccharide extracted from Phellinus linteus (PL) mushroom possess antitumor activity. We previously have demonstrated that PL has direct antitumor effect through apoptosis and G2/M cell cycle blockade in SW480 human colon cancer cells. However, the molecular mechanisms responsible for antitumor and antiinvasive behavior of PL remain to be explored. Employing SW480 colon cancer cells which are overexpressed B-catenin, we demonstratd that PL significantly inhibited cellular proliferation and remarkable decrease of B-catenin expression on Western blot and indirect immunofluorescence detection in PL treated cells. Cyclin D1, one of the B-catenin controlled downstream genes and TCF/LEF transcription activity were also significantly reduced when PL was treated. PL inhibited in vitro invasion and motility of SW480 cells and the activity of matrix metalloproteinase (MMP)-9 on zymography. In addition, PL inhibited human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice were significantly inhibited with PL treatment in a dose-dependent manner. Immunohistochemical analysis of xenografted tumor tissue showed that apoptotic index was markedly increased and nuclear staining of b-catenin was decreased. However, the proliferation index and microvessel density were significantly decreased. These data demonstrate that PL downregulates Wnt/b-catenin signaling pathway and inhibits multiple steps in tumor invasion in certain colon cancer cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5646.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM10-5646
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    Abstract 4654: Docosahexaenoic acid induces autophagy through reactive oxygen species /mTOR pathway in p53 mutant cancer cells
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4654-4654
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4654-4654
    Abstract: Our previous studies reported that docosahexaenoic acid (DHA) induces autophagy through p53 inhibition in the wild-type p53 cancer cells. This study attempts to elucidate the molecular mechanism underlying DHA-induced autophagy in PC3 and DU145 prostate cancer cells harboring mutant p53. DHA increased both the level of microtubule-associated protein light-chain 3 (LC3) and the number of autophagic vacuoles. Autophagic flux assay confirmed that DHA-induced increase in LC3-II and autophagic vesicles was an outcome of autophagic process activation, indicating that DHA also induces autophagy in p53 mutant cancer cells. DHA treatment also increased the level of reactive oxygen species (ROS) as measured by dihydroethidine staining, and pretreatment of an antioxidant, N-acetylcysteine (NAC), significantly inhibited the ROS production as well as autophagy induced by DHA, suggesting that ROS regulates the autophagic process triggered by DHA. Further experiments showed that the mechanism of DHA-induced autophagy associated with ROS production was related to a decrease in the activity of mammalian target of rapamycin (mTOR). NAC remarkably restored the decreases in the levels of phospho-mTOR and 4EBP, an mTOR downstream molecule, induced by DHA as analyzed by the Western blot assay. Furthermore, the level of phospho-AMPK, which negatively regulates mTOR was increased, while phospho-Akt was reduced during the DHA-induced autophagy, indicating the involvement of AMPK and Akt signalings. Collectively, our results demonstrate that DHA induces autophagy through the ROS-mediated mTOR inactivation in p53 mutant prostate cancer cells. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2011-0006232]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4654. doi:1538-7445.AM2012-4654
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-4654
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    Online Resource
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    Abstract 862: Expression of the fat-1 gene retards the growth of cervical cancer cells in vitro and in vivo
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 862-862
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 862-862
    Abstract: Omega 3-polyunsaturated fatty acids (ω3-PUFAs) are known to inhibit proliferation of cancer cells; in contrast, ω6-PUFAs promote the growth of cancer cells. The fat-1 gene of the Caenorhabditis elegans encodes a ω3-desaturase that catalyzes the conversion ω6-PUFAs to ω3-PUFAs and then increases the amount of ω3-PUFAs. The objective of this study is to examine the effect of fat-1 gene expression on HeLa and SiHa human cervical cancer cells. Fat-1 gene stable cell lines (f-HeLa and f-SiHa) were established from HeLa and SiHa cells, respectively. The expression of fat-1 gene significantly inhibited cervical cancer cell proliferation and f-HeLa cells showed an increase in the proportion of cells in G2/M phase comparing with the cells expressing the control vector (c-HeLa). In addition, when treating HeLa cells with docosahexaenoic acid (DHA), an enhanced proportion of cells in the G2/M phase was also observed, indicating that fat-1 gene inhibited cervical cancer cell proliferation by inducing a G2/M phase cell-cycle arrest. Furthermore, transwell migration assay for invasion showed a reduction of cell migration in the f-HeLa cells when compared with the c-HeLa cells. Finally, the growth of f-HeLa cells in vivo was significantly reduced comparing with the c-HeLa cells when inoculated into nude mice. Taken together, these results suggest that the expression of fat-1 gene prevents cervical tumor growth and indicate a cancer therapeutic approach of the ω3-PUFAs. Therefore, a stable cell line of fat-1 gene is useful to study the anti-cancer effects of ω3-PUFAs. [This research was supproted by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (E00026 and R13-2007-020-01000-0)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 862. doi:10.1158/1538-7445.AM2011-862
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-862
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
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    Apicularen A Induces Cell Death through Fas Ligand Up-Regulation and Microtubule Disruption by Tubulin Down-Regulation in HM7 Human Colon Cancer Cells
    American Association for Cancer Research (AACR) ; 2007
    In:  Clinical Cancer Research Vol. 13, No. 21 ( 2007-11-01), p. 6509-6517
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 21 ( 2007-11-01), p. 6509-6517
    Abstract: Purpose: Apicularen A has been shown to cause growth inhibition and apoptosis in several cancer cell lines. However, the mechanisms of apicularen A–induced cell death and in vivo effects remain unclear. In this study, we investigated the molecular mechanisms of apicularen A–induced cell death in HM7 human colon cancer cells in vitro and anticancer activity in vivo. Experimental Design: We tested cytotoxicity with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, apoptosis with DNA fragmentation assay, mitochondrial membrane potential, and cell cycle with fluorescence-activated cell sorting. Caspase activation was done by fluorometry. Alterations of microtubule structure, tubulin protein, and mRNA level were assessed by immunofluorescence, Western blot, and reverse transcription-PCR. In vivo studies were assessed using nude mice tumor cell growth in xenograft model and liver colonization assay. Results: Apicularen A treatment of HM7 cells inhibited cell growth and this inhibition was partially rescued by z-VAD-fmk. Apicularen A caused accumulation of sub-G1-G0, DNA fragmentation, Fas ligand induction, and activation of caspase-8 and caspase-3, but mitochondrial membrane potential was not changed. Furthermore, β-tubulin protein and mRNA were decreased by apicularen A, but in vitro polymerization of tubulin was not affected. Concurrently, apicularen A–treated cell showed disruption of microtubule architecture. In in vivo studies, apicularen A reduced tumor volume by ∼72% at the end of a 15-day treatment. Moreover, apicularen A reduced liver colonization as much as 95.6% (50 μg/kg/d). Conclusion: Apicularen A induces cell death of HM7 cells through up-regulating Fas ligand and disruption of microtubule architecture with down-regulation of tubulin level. These findings indicate that apicularen A is a promising new microtubule-targeting compound.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-07-1428
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 10
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    Abstract 4175: Reactive oxygen species-dependent ERK and JNK activation is important to docasahexaenoic acid-induced cell cytotoxicity in human ovarian cancer cells
    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4175-4175
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4175-4175
    Abstract: Although abundant experimental evidences show that the Omega-3 polyunsaturated fatty acids (≥3-PUFAs) prevent carcinogenesis, the exact molecular mechanisms of the anti-cancer actions of α3-PUFAs in ovarian cancer remain incompletely understood. In the present study, the effectiveness of docosahexaenoic acid (DHA), a α3-PUFA, against ovarian cancer cells was investigated. We found that DHA induced cell cytotoxicity in three ovarian cancer cells including PA-1, MDAH2774 and ID8. DHA treatment inhibited the cell proliferation of PA-1 cells in a dose- and time-dependent manner. Meanwhile, DHA-treated ovarian cancer cells showed increased levels of caspase-3 activity, Annexin-V staining positive cells, TUNEL-positive cells and the portion of sub-G1 cells, suggesting that DHA-induced cell death is mainly associated with apoptosis. Western blot and immunocytochemistry assays revealed that DHA also remarkably increased the levels of phospho-ERK and phospho-JNK in both cytosol and nucleus. Moreover, knockdown ERK and JNK by small interfering RNAs partially attenuated the apoptosis induced by DHA, indicating that ERK and JNK activation is responsible for the apoptosis in DHA-treated ovarian cancer cells. In addition, we determined that the activation of ERK and JNK was associated with the reactive oxygen species (ROS) production induced by DHA. ROS scavenger, N-acetyl-L-cysteine (NAC), almost completely blocked the ERK and JNK phosphorylation as well as the apoptosis triggered by DHA. Together, these results indicate that DHA induces ROS and the ROS-dependent ERK and JNK activation is important to DHA-induced cell cytotoxicity in human ovarian cancer cells. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0006232 and 2011-0003060)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4175. doi:1538-7445.AM2012-4175
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2012-4175
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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