المؤلفون: H, Kaneko, H, Hibasami, K, Mori, Y, Kawarada, K, Nakashima

المصدر: Anticancer research. 18(2A)

مصطلحات موضوعية: Mitoguazone, Biogenic Polyamines, Tumor Cells, Cultured, Humans, Antineoplastic Agents, Apoptosis, Breast Neoplasms, Female, Spermine, Cell Division

الوصف: We have investigated the antiproliferative effects of a polyamine synthesis inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MCBCP), on human breast cancer MRK-nu-1 cells. MGBCP inhibited tumor growth of MRK-nu-1 cells in a dose-dependent manner as the polyamine contents in the cells decreased. Moreover, morphological changes indicating blebbing and chromatin condensation were observed in the MGBCP-treated cells, and hypodiploid subpopulations containing apoptotic cells were clearly detected in the profile of flow cytometric analysis. The number of characteristic oligonucleosome-sized fragments also increased as the concentration of MGBCP increased. The apoptotic effects of MGBCP were partially prevented by the addition of exogenous spermine. The results presented here suggest that, in addition to reducing the growth rate, MGBCP can induce apoptotic cell death in MRK-nu-1 human breast cancer cells by the reduction of intracellular concentrations of polyamines.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::843f9618b61de8ef4956f78393d6f05fTest
https://pubmed.ncbi.nlm.nih.gov/9615737Test

المؤلفون: K, Mori, H, Hibasami, N, Satoh, J, Sonoda, T, Yamasaki, M, Tajima, S, Higuchi, H, Wakabayashi, H, Kaneko, A, Uchida, K, Nakashima

المصدر: Anticancer research. 17(4A)

مصطلحات موضوعية: Osteosarcoma, Mitoguazone, Polyamines, Tumor Cells, Cultured, Humans, Apoptosis, DNA Fragmentation

الوصف: Our previous experiments have shown that methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine synthesis inhibitor, suppresses the growth of osteosarcoma cells repressing their intracellular polyamine levels, and that this inhibition of cell growth is only partially reversed by the addition of polyamines. In the present study, we found evidence indicating that the incomplete recovery of cell growth by the addition of polyamines to the polyamine-depleted cells was due to programmed cell death (apoptosis) induced by MGBCP. Morphological changes showing blebbing and chromatin condensation were observed in MGBCP-treated cells, and hypodiploid subpopulations containing apoptotic cells were clearly visible in the profile of flow cytometric analysis. Characteristic oligonucleosomal-sized fragments were increased as the concentration of MGBCP was increased. The results presented here suggest that in addition to reducing the growth rates, MGBCP can induce apoptotic cell death in three human osteosarcoma cell lines.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::85135aa4b34fb6685262d6d8382664d3Test
https://pubmed.ncbi.nlm.nih.gov/9252651Test

المؤلفون: K, Mori, H, Hibasami, J, Sonoda, S, Fujinami, S, Sekiguchi, M, Tajima, T, Yamazaki, S, Higuchi, A, Uchida, K, Nakashima

المصدر: Anticancer research. 16(5A)

مصطلحات موضوعية: Osteosarcoma, Mitoguazone, Cell Cycle, G1 Phase, Mitotic Index, Tumor Cells, Cultured, Humans, Antineoplastic Agents, Drug Screening Assays, Antitumor, S Phase

الوصف: Our previous experiments have indicated that the antitumor effects of a polyamine biosynthetic inhibitor, methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), on human osteosarcoma cell lines such as MG-63, G-292 and HOS cells are obtained by its action depleting the cellular polyamine contents. In the present study, the effects of polyamine depletion by MGBCP on the cell cycle progression in these osteosarcoma cell lines were investigated by flow cytofluormetric analysis. MGBCP arrested the tumor cells at the G1 phase by preventing the G/S phase transition. Mitotic indexes (MIs) in these MGBCP-inhibited tumor cells were also decreased. These findings suggest that MGBCP suppresses the cell cycle progression in osteosarcoma MG-63, G-292 and HOS cells by inhibiting intracellular polyamine biosynthesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::0a2463ddbc7fd82aa3dec9e6699a8773Test
https://pubmed.ncbi.nlm.nih.gov/8917352Test

المؤلفون: J, Sonoda, H, Hibasami, H, Yamada, S, Fujinami, K, Nakashima, Y, Ogihara

المصدر: Anticancer research. 15(3)

مصطلحات موضوعية: Osteosarcoma, Mitoguazone, Dose-Response Relationship, Drug, Cell Survival, Spermidine, Antineoplastic Agents, Bone Neoplasms, Cell Line, Kinetics, Methotrexate, Doxorubicin, Polyamines, Putrescine, Tumor Cells, Cultured, Humans, Drug Interactions, Spermine, Ifosfamide, Drug Screening Assays, Antitumor

الوصف: The antitumor effect of a polyamine biosynthetic pathway inhibitor methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP) on human osteosarcoma cell lines such as KHOS-240S, MG-63 and G-292 cells, and its effect in combination with anticancer drugs such as methotrexate (MTX), adriamycin (ADM) and 4-hydroperoxyfosfamide (HIFO) have been investigated. The growth of these cultured osteosarcoma cells was inhibited by MGBCP in a dose-dependent manner. Spermidine and spermine levels were dose-dependently depressed in these MGBCP-treated osteosarcoma cells. The antitumor effect of MGBCP was additively potentiated by combined treatment with MTX, ADM and HIFO, respectively.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::78aaa899366f1b0f2e871b4321547995Test
https://pubmed.ncbi.nlm.nih.gov/7645980Test

المؤلفون: H, Hibasami, T, Tsukada, S, Shirakawa, T, Narita, M, Inagaki, K, Nakashima

المصدر: Anticancer research. 14(2A)

مصطلحات موضوعية: Male, Mitoguazone, Time Factors, Spermidine, Antineoplastic Agents, Piperazines, Cell Line, Mice, Polyamines, Putrescine, Tumor Cells, Cultured, Animals, Humans, Leukemia L1210, Crosses, Genetic, Cell Nucleus, Dose-Response Relationship, Drug, Leukemia P388, Drug Synergism, Leukemia, Lymphoid, Mice, Inbred C57BL, Kinetics, Mice, Inbred DBA, Female, Spermine, Drug Screening Assays, Antitumor, Cell Division

الوصف: Antiproliferative effects of 1,1'-ethylenedi-4-isobutoxy-carbonyloxymethyl-3,5-d iox opiperazine (MST-16), an inhibitor of topoisomerase II, in combination with methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP), an inhibitor for polyamine biosynthetic enzymes, were investigated using cultured human lymphoid cells and leukemic mice. The combined treatment of human Molt 4B lymphoid cells with MST-16 and MGBCP resulted in greater suppressions of cellular polyamine and protein biosyntheses and decrease of cell number than in the cells treated with either drug alone. Inhibition of macromolecule biosyntheses by MGBCP was additively potentiated by simultaneous treatment with MST-16. In vivo experiments, the combination of MST-16 and MGBCP markedly prolonged the survival time of mice bearing P388 or L1210 leukemia. These results suggest that good antitumor activity of combined treatment with MST-16 and MGBCP resulted from the diminution of DNA condensation and cellular proliferation caused by inhibition of topoisomerase II with MST-16 and by polyamine depletion with MGBCP.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::b589a7384fea4fcf1a44b44fb7bf3404Test
https://pubmed.ncbi.nlm.nih.gov/8017861Test

المؤلفون: A, Sjöholm, R, Larsson, P, Nygren

المصدر: Anticancer research. 13(4)

مصطلحات موضوعية: Eflornithine, Mitoguazone, Dose-Response Relationship, Drug, Cell Survival, Spermidine, DNA, Neoplasm, Ornithine Decarboxylase, Kinetics, Urinary Bladder Neoplasms, Verapamil, Vincristine, Polyamines, Putrescine, Tumor Cells, Cultured, Humans, Spermine, Cell Division

الوصف: The significance of the polyamines putrescine, spermidine and spermine for the neoplastic proliferation of the human renal carcinoma cell line ACHN was investigated. For this purpose cells were cultured in vitro for 4 days with or without the addition of pathway inhibitors of polyamine biosynthetic enzymes. It was found that treatment of ACHN cells with the specific ornithine decarboxylase (ODC) inhibitor difluoromethylornithine (DFMO) resulted in profound decreases of ODC activity, polyamine content and cell proliferation rates along with a compensatory increase in S-adenosylmethionine decarboxylase (SAMDC) activity. Ethylglyoxal bis(guanylhydrazone) (EGBG), a SAMDC inhibitor, evoked a similar reduction of cell proliferation and contents of spermidine and spermine. EGBG also seemed to stabilize SAMDC, as evidenced by a highly enhanced SAMDC activity during enzyme assays in the absence of the inhibitor. Furthermore, EGBG treatment caused on activation of ODC and a subsequent build-up of putrescine. The impact on polyamine contents and proliferation rates were synergistic when the inhibitors were used in combination. None of the inhibitors alone exerted a cytocidal activity. It is concluded that polyamines may be implicated in the regulation of the neoplastic proliferation of cultured human renal carcinoma cells and that polyamine synthesis inhibitors may prove valuable in clinical treatment of this disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::602b382b6381f1bf8c6bb3c454af2699Test
https://pubmed.ncbi.nlm.nih.gov/8352568Test

المؤلفون: H, Hibasami, S, Takaji, T, Murata, K, Nakashima

المصدر: Anticancer research. 11(4)

مصطلحات موضوعية: Mitoguazone, Cell Survival, Spermidine, Antineoplastic Agents, DNA, Neoplasm, Benzylisoquinolines, Cell Line, Neoplasm Proteins, Kinetics, Alkaloids, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Polyamines, Putrescine, Humans, Spermine, RNA, Neoplasm, Cell Division

الوصف: Antiproliferative effects of cepharanthine, a biscoclaurine alkaloid, in combination with methylglyoxal bis (cyclopentylamidinohydrazone) (MGBCP), an inhibitor for polyamine biosynthesis, were investigated. The antitumor activity of MGBCP on human leukemic cells was potentiated by cepharanthine. Cellular polyamine levels in the leukemic cells treated with both MGBCP and cepharanthine were much lower than those of the cells treated with MGBCP alone. On the contrary, the cellular MGBCP concentration was much higher in the cepharanthine-treated leukemic cells. Thus cepharanthine was considered to enhance the incorporation of MGBCP into the leukemic cells. The combination of MGBCP and cepharanthine resulted in a greater suppression of macromolecule synthesis in the cells that might have caused the greater suppression of tumor cell growth.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::7c3670795ef9f864bfa3d9412aa8074fTest
https://pubmed.ncbi.nlm.nih.gov/1746912Test