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  • 1
    Electronic Resource
    Electronic Resource
    The effect of NC-190, a novel antitumor compound, on the cell-cycle progression of HeLa S3 cells (1993)
    Springer
    Cancer chemotherapy and pharmacology 32 (1993), S. 249-254 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A novel antitumor compound,N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190), has potent antitumor activity against in vivo and in vitro tumor models. In this study, we evaluated the cell-cycle effect of NC-190 on cultured HeLa S3 cells using DNA/bromodeoxyuridine(BrdU) bivariate flow-cytometric analysis. Continuous treatment with NC-190 for 72 h inhibited the growth of cultured Hela S3 cells in a concentration-dependent manner. Its 50% growth-inhibitory concentration (IC50) was 0.039 μg/ml (0.085 μM). The cell-cycle effects of NC-190 were dependent on the drug concentration and the treatment period. Continuous treatment with a low concentration (0.1 μg/ml) of NC-190 inhibited cell-cycle progression from the G2 to the M phase, resulting in G2 accumulation. With increasing concentration, NC-190 delayed cell-cycle traverse in the S and G2 phases. At a higher (10 μg/ml) concentration of NC-190, cell-cycle traverse was prevented in the G1, S, and G2 phases. Under such conditions, NC-190 increased the numbers of S0-phase cells (the cells with DNA content corresponding to that of S-phase cells, but without BrdU incorporation). Treatment for 2 h with NC-190 at 10 μg/ml induced the accumulation of cells in the G2 phase, and cell debris was observed at 48 and 72 h after drug treatment. During this time, the proportion of cells in the S0 phase increased up to 19.2%. The colcemid-induced mitotic cell accumulation was delayed by NC-190 at a concentration of 0.1 μg/ml at 4 h after the addition of the drugs. The addition of higher concentrations (1 and 10 μg/ml) of NC-190 inhibited the increase in the mitotic fraction completely. These results indicate that the mechanism involved in the G2 arrest and the increment of S0-phase cells caused by NC-190 is associated with this compound-induced cell death.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686168
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    In vivo activity on murine tumors of a novel antitumor compound, N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]phenazine-6-carboxamide sodium salt (NC-190) (1989)
    Springer
    Cancer chemotherapy and pharmacology 23 (1989), S. 135-139 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A novel antitumor compound, N-β-dimethylaminoethyl 9-carboxy-5-hydroxy-10-methoxybenzo[a]-phenazine-6-carboxamide sodium salt (NC-190) was evaluated for its antitumor activity in experimental murine tumor systems. In the initial studies with P388 leukemia (i.p.-i.p.), NC-190 led to an increase of 〉200% in life span (ILS), and 75% of the mice were alive on day 30, when the optimal dose (50 mg/kg, days 1–5) was given. Additionally, the compound had significant activities against i.p. inoculated mouse L1210 leukemia, B16 melanoma, M5076 reticulum cell sarcoma, sarcoma 180, mouse hepatoma MH134, and rat Yoshida sarcoma and Yoshida ascites hepatoma AH130. The optimal dose resulted in a 〉280% ILS with a 30-day survival of 50% in mice with L1210 leukemia (100 mg/kg, days 1–5), a 156% ILS in mice with B16 melanoma (50 mg/kg, days 1–5), a 98% ILS with a 90-day survival of 25% in mice with M5076 reticulum cell sarcoma (25 mg/kg, days 1, 5, 9, and 13), a 〉300% ILS with a 60-day survival of 50% in mice with sarcoma 180 (50 mg/kg, days 3–10), a 148% ILS with a 60-day survival of 25% in mice with MH134 (25 mg/kg, days 1–5), a 129% ILS with a 60-day survival of 12.5% in rats with Yoshida sarcoma (12.5 mg/kg, day 3–10), and a 〉161% ILS with a 60-day survival of 50% in rats with AH130 (6.3 mg/kg, days 3–10). In the experiments with s.c. inoculated tumors, NC-190 not only inhibited tumor growth, but also increased the life span of mice with Lewis lung carcinoma or B16 melanoma. The 60-day survivors accounted for 60% and 30% in mice with Lewis lung carcinoma and B16 melanoma, respectively. The compound significantly inhibited the spontaneous lung metastasis of Lewis lung carcinoma by more than 90% when eight daily i.v. injections were given. NC-190 was active by the i.p., s.c., and i.v. routes. Five consecutive daily i.p. doses (days 1–5) were more effective than a single dose (day 1), two doses (days 1 and 5), or three doses (days 1, 5, and 9). NC-190 warrants further study as a potential antineoplastic agent against human neoplasms, as it has a broad spectrum of antitumor activity and inhibits metastasis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00267943
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    Paper (German National Licenses)
    Fulltext
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