ライフサイエンスコーパス: DENSPM

1 DENSPM (N1, N11-diethylnorspermine), a polyamine analog

2 DENSPM treatment inhibited the transient increases in pu

3 been observed for the DENSPM/(2R,10R)-(HO)(2)DENSPM pair.

4 comparison of the toxicity of (R, R)-(HO)(2)DENSPM with that of DENSPM at subchronic doses revealed

5 As with DENSPM and (2R,10R)-(HO)(2)DENSPM, both cyclopropyl analogues diminished ornithine

6 oxylated analogues, especially (R, R)-(HO)(2)DENSPM, were much less effective at upregulation than th

7 l-2,10-dihydroxynorspermine [(2R,10R)-(HO)(2)DENSPM] after 96 h of treatment; the activity was compar

8 l-2,10-dihydroxynorspermine [(2S,10S)-(HO)(2)DENSPM] at 96 h.

9 Although the analog DENSPM has been regarded as the most potent inducer of S

10 ifference in cell number between control and DENSPM-treated cultures.

11 ssion analysis showed that combined 5-FU and DENSPM treatment activated caspase 9, but not caspase 3,

12 ur results showed that simultaneous 5-FU and DENSPM, a spermine analogue, synergistically increased t

13 11-diethylnorspermine (DE-333, also known as DENSPM or BENSPM) is regarded as the most potent known i

14 11-diethylnorspermine (DE-333, also known as DENSPM) is currently undergoing Phase I clinical trials

15 nism of cell resistance to analogues such as DENSPM.

16 ollowing G2/M transition was not affected by DENSPM treatment.

17 hibition of polyamine biosynthesis caused by DENSPM was the S phase.

18 ons which blocked protein synthesis, that by DENSPM took place at concentrations which did not.

19 After 144 h of exposure to JURKAT cells, DENSPM reduces putrescine to below detectable limits and

20 rmidine pools, but less effectively than did DENSPM and its derivatives.

21 mine analogue N(1),N(11)-diethylnorspermine (DENSPM) inhibits cell growth by down-regulating polyamin

22 N(1),N(11)-Diethylnorspermine (DENSPM) is a polyamine analogue with clinicalrelevance a

23 h than either N(1),N(11)-diethylnorspermine (DENSPM) or (2R,10R)-N(1),N(11)-diethyl-2,10-dihydroxynor

24 i.v.-administered N1,N11-diethylnorspermine (DENSPM) are evaluated in Cebus apella primates, and the

25 polyamine analog N1,N11-diethylnorspermine (DENSPM) causes rapid apoptosis in human melanoma SK-MEL-

26 olyamine analogue N1,N11-diethylnorspermine (DENSPM) increased SSAT activity in the transgenic fibrob

27 N1,N11-diethylnorspermine (DENSPM) is a polyamine analog that down-regulates polyam

28 metabolism, i.e. N1,N11-diethylnorspermine (DENSPM) or alpha-difluoromethylornithine (DFMO), have sy

29 e spermine analog N1,N11-diethylnorspermine (DENSPM), cell proliferation ceased; this was clearly app

30 s SSAT activity, N1, N11-diethylnorspermine (DENSPM), increases SSAT mRNA in MALME-3M human melanoma

31 yamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N14-diethylhomospermine (DEHSPM), 1,6,12-tri

32 bitory effects of N1,N11-diethylnorspermine (DENSPM)-a polyamine analogue also undergoing Phase 1 cli

33 t drug (e.g., N(1),N(11)-diethylnorspermine [DENSPM]) at 1 microM; however, S-adenosylmethionine deca

34 and ML-IAP loss as well as apoptosis during DENSPM treatment.

35 Upstream to these events, DENSPM downregulates polyamine biosynthesis and potently

36 Unlike the hydroxylated DENSPM compounds, both cyclopropyl norspermines substant

37 ree kinases but failed to alter apoptosis in DENSPM-treated SK-MEL-28 cells.

38 letion and to caspase-dependent apoptosis in DENSPM-treated SK-MEL-28 cells.

39 enerality of this effect was demonstrated in DENSPM-treated A375 and LOX human melanoma cells.

40 which the compounds lower spermine levels is DENSPM > DEHSPM > (4,5) triamine > (5,5) triamine.

41 e accumulating to high intracellular levels, DENSPM was much less effective than spermine at down-reg

42 t of SK-MEL-28 human melanoma with 10 microM DENSPM.

43 Treatment of SK-MEL-28 cells with 10 muM DENSPM in the presence of 83 nM siSSAT selectively preve

44 We also observed that structural analogs of DENSPM which differentially induced SSAT and apoptosis l

45 to induce vacuoles and various analogues of DENSPM were used to probe the structural specificity of

46 In dogs, the organ concentration of DENSPM follows the order kidney >> liver approximately =

47 the accumulation of extremely high levels of DENSPM without increasing growth inhibition.

48 tion correlated temporally with the onset of DENSPM induced apoptosis or growth inhibition.

49 A panel of DENSPM analogues differing only in their ability to indu

50 seeding cells in the absence or presence of DENSPM.

51 Although the metabolic processing of DENSPM (i.e., deethylation and deaminopropylation) in do

52 pre-treatment and post-treatment regimens of DENSPM and DFMO were antagonistic to 5-FU depending on c

53 oxicity of (R, R)-(HO)(2)DENSPM with that of DENSPM at subchronic doses revealed that the neurologica

54 ss effective at upregulation than the parent DENSPM.

55 Of the four polyamines, DENSPM and DEHSPM are potent at lowering intracellular h

56 siSSAT also prevented DENSPM-induced cytochrome c release and caspase-3 cleava

57 mRNA in HEK-293 cells by >80% and prevented DENSPM-induced SSAT mRNA by 95% in SK-MEL-28 cells.

58 Similarly, DENSPM was less able to induce spermidine/spermine N1-ac

59 Subsequently, we found that DENSPM markedly lowered survivin and ML-IAP protein (but

60 Taken together, the findings indicate that DENSPM-induced apoptosis is at least partially initiated

61 ate the apoptotic response, we observed that DENSPM treatment of SK-MEL-28 cells for 30 h led to cyto

62 ata are consistent with the probability that DENSPM is sequestered to high concentrations in lysosoma

63 This study reveals that DENSPM potently activates the mitogen-activated protein

64 Our results show that DENSPM treatment did not affect the progression of the c

65 he same phenomenon had been observed for the DENSPM/(2R,10R)-(HO)(2)DENSPM pair.

66 acetyltransferase (SSAT) upregulation in the DENSPM series.

67 Three DENSPM analogues that differentially induced SSAT activi

68 ys in determining the biological response to DENSPM treatment is dependent on the genetic environment

69 NA levels and formed vacuoles in response to DENSPM, whereas those resistant to 10 microM CGP-48664 d

70 enic fibroblasts were much more sensitive to DENSPM-induced growth inhibition.

71 se data suggest a sequence of events whereby DENSPM induction of SSAT leads to loss of IAP proteins a

72 With DENSPM treatment, spermidine pools were more rapidly dep

73 As with DENSPM and (2R,10R)-(HO)(2)DENSPM, both cyclopropyl anal

74 report that treatment of CHO/664 cells with DENSPM results in the formation of numerous large cytopl

75 ysteine, which when used in combination with DENSPM, decreased MAPK activation and as previously show

76 nd suggest that the combination of 5-FU with DENSPM has potential for development as therapy for colo

77 combination of either protein inhibitor with DENSPM or spermine produced an additive increase in SSAT

78 aled that the neurological effects seen with DENSPM were now absent.