NSC697923 is a potent UBE2N (ubiquitin-conjugating enzyme E2 N, Ubc13) inhibitor. NSC697923 induces neuroblastoma (NB) cell death via promoting nuclear importation of p53 in p53 wild-type NB cells. NSC697923 also induces cell death in p53 mutant NB cells by activation of JNK-mediated apoptotic pathway. NSC697923 inhibits DNA damage and NF-κB signaling. Antitumor activity.
性状
Solid
体外研究(In Vitro)
NSC697923 (0-5 μM; 24 hours) shows cytotoxic effect on NB cell lines.
NSC697923 (3?μM; 2 hours) can also induce apoptosis in p53 mutant NB cells by activation of JNK-mediated apoptotic pathway.
NSC697923 induces apoptosis in p53 wild-type NB cell lines by promoting p53 nuclear translocation and activation.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay
Cell Line:
Three MYCN-amplified cell lines: IMR32, NGP, NB19 and three MYCN-non-amplified cell lines: CHLA-255, SK-N-AS, and SH-SY5Y
Concentration:
0-5 μM
Incubation Time:
24 hours
Result:
Significantly reduced NB cells viability in a dose-dependent manner. Also induced cell death in the p53 non-functional cell line SK-N-AS and p53 partially functional cell line NB-19.
Western Blot Analysis
Cell Line:
p53 wild-type SH-SY5Y and IMR32 cells
Concentration:
3?μM
Incubation Time:
2 hours
Result:
Induced expression of p53-targeted gene p21 as well as the cleavage of caspase 3 in two p53 wild-type cell lines SH-SY5Y and IMR32.
体内研究(In Vivo)
NSC697923 (5?mg/kg; i.p.; daily for 10 days) suppresses NB tumor growth in SH-SY5Y and NGP xenografts.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
5- to 6-week-old female athymic Ncr nude mice (orthotopic mouse model of NB; SH-SY5Y and NGP xenografts)
Dosage:
5?mg/kg
Administration:
I.p.; daily for 10 days
Result:
Significant tumor regression in both SH-SY5Y and NGP xenografts.