Dehydroaltenusin 脱氢阿霉素是真核DNA 聚合酶 α (DNA polymerase α) 的小分子选择性抑制剂，一种由真菌产生的抗生素，其 IC50值为 0.68 μM。 Dehydroaltenusin 对哺乳动物 polα 活性的抑制作用模式对 DNA 模板引物 (Ki=0.23 μM) 是竞争性的，对 2'-脱氧核糖核苷 5'-三磷酸底物是非竞争性的 (Ki=0.18 μM)。
Dehydroaltenusin 在 S 期阻止癌细胞周期并触发凋亡 apoptosis。
Dehydroaltenusin 在体内具有抗人类腺癌肿瘤的抗肿瘤活性。
IC50: 0.68 μM (DNA polymerase α)
Dehydroaltenusin (38.0-44.4 μM; 24 hours) inhibits cell growth in a dose-dependent manner and the LD
50
values varies from 38.0 to 44.4 μM.
Dehydroaltenusin (38.0 μM; 6 hours) inhibits cell growth by blocking the S-phase of DNA replication.
Dehydroaltenusin (75.0 μM; 24 hours) has a strong apoptotic effect on human cancer cells, DNA ladders can be detected after 12 h of incubation with dehydroaltenusin.
Cell Proliferation Assay
|
Cell Line:
|
Human cancer cell line: A549, BALL-1, HeLa and NUGC-3 cells
|
|
Concentration:
|
38.0-44.4 μM
|
|
Incubation Time:
|
24 hours
|
|
Result:
|
Inhibited cell growth of human cancer cell lines.
|
Cell Cycle Analysis
|
Cell Line:
|
HeLa cells
|
|
Concentration:
|
38.0 μM
|
|
Incubation Time:
|
6 hours
|
|
Result:
|
Decreased to 45% of the control value after 6 h of incubation [
3
H]-thymidine.
|
Apoptosis Analysis
|
Cell Line:
|
HeLa cells
|
|
Concentration:
|
75.0 μM
|
|
Incubation Time:
|
12-24 hours
|
|
Result:
|
Detected DNA ladders after 12 hours of incubation.
|
Dehydroaltenusin (injection; 20 mg/kg; 2-day intervals; 12-39 days) shows suppressed tumor growth from 21 days.
|
Animal Model:
|
Nude mice bearing HeLa solid tumors
|
|
Dosage:
|
20 mg/kg
|
|
Administration:
|
Injection; 20 mg/kg; 2-day intervals; 12-39 days
|
|
Result:
|
Suppressed tumor growth.
|
