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Application of camptothecin derivative in drug preparing process for treating marrow originate leukemia

A technology for myeloid leukemia and derivatives is applied in the application field of camptothecin derivatives in the preparation of drugs for the treatment of myeloid leukemia, and achieves the effects of good medicinal prospects and strong pharmacological effects

Inactive Publication Date: 2005-09-07
RUIJIN HOSPITAL ATTACHED TO SHANGHAI NO 2 MEDICALUNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although there are many studies on camptothecin derivatives, so far, there is no research report on the application of camptothecin derivatives NSC606985 in the preparation of drugs for the treatment of acute leukemia

Method used

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  • Application of camptothecin derivative in drug preparing process for treating marrow originate leukemia
  • Application of camptothecin derivative in drug preparing process for treating marrow originate leukemia
  • Application of camptothecin derivative in drug preparing process for treating marrow originate leukemia

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Experimental program
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Embodiment 1

[0049] Application of camptothecin derivative NSC606985 in preparation of medicine for treating myeloid leukemia

[0050] Step 1. Cell culture and processing

[0051] Acute promyelocytic leukemia NB4 cells (provided by Dr. Michael Lannotte), acute monocytic leukemia U937 cells and chronic myelogenous leukemia K562 cells (from the cell bank of Shanghai Institute of Biological Sciences, China) were all incubated at 37°C, 5% Under the condition of CO2-95% air humidity, culture was carried out in RPMI-1640 medium containing 10% heat-inactivated fetal calf serum (FCS, Hyclone, Logan, UT). 2-5×10 experimental cells 5 cells / ml and incubated with desired concentrations of NSC606985 in the presence / absence of the PKCδ-specific inhibitor rottelin and the caspase-3 inhibitor z-DEVD-fmk. NSC606985 (provided by the National Cancer Institute Anticancer Drug Screening Standard Drug Database) was dissolved in double distilled water and prepared as a 25 μM stock solution. Rottlerin (BIOMOL,...

Embodiment 2

[0061] Evaluation of the effect of camptothecin derivative NSC606985 on myeloid leukemia

Embodiment 2-1

[0063] Nanomolar concentration of NSC606985 induces apoptosis in promyelocytic leukemia cell lines

[0064] In the APL cell line NB4 cells, NSC606985 inhibited cell growth in a time-dose dependent manner ( Figure 1B , left), which is consistent with decreased cell viability ( Figure 1B ,right). This inhibitory effect was observed at nanomolar concentrations. After 48 hours of treatment, 6.25nM NSC606985 caused 48.2 ± 2.8% cell death, and 50nM and 100nM NSC606985 caused almost all cell death ( Figure 1B ,right). Further evidence supports that NSC606985 induces cell death through apoptosis. NB4 cells treated with NSC606985 showed profound cell morphological changes, such as chromosome condensation, nuclear rupture without cell membrane damage and other apoptosis characteristics ( Figure 1C ). Analysis of nuclear DNA content by flow cytometry showed that after NSC606985 induction, due to the degradation and leakage of nuclear DNA, hypoploid cells (also known as sub-G1 c...

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Abstract

The present invention concerns application of camptothecine derivation NSC606985 in preparing drug for acute leukemia. NSC606985 of nano-molar concentration can induce cell line NB4 and cell U937 of leukemia to apoptosis. On the aspect of inducing apoptosis, NSC606985 can induce quickly transmembrane potential of mitochondrion (deltaWm) to falling and activation of caspase-3. Hydrolysis and activation of protein kinase induced C delta (PKC delta) by NSC606985 plays key role and starting effect during these processes. Specific inhibitor rottlerin for PKC delta can restrain entirely the falling of mitochondrion deltaWm and activation of caspase-3 and the Specific inhibitor Z-DEVD-fmk for caspase-3 just weaken partly activation of PKC delta and cell apoptosis. NSC606985 restrains marked clone forming ability of hemopoietic progenitor cell in fresh marrow of patient of acute medullary leukemia. So NSC606985 is potential active drug for treating leukemia.

Description

technical field [0001] The invention relates to the application of camptothecin derivative NSC606985 in the preparation of medicines for treating myeloid leukemia. Specifically, the application of camptothecin derivative NSC606985 in nanomolar concentration in the preparation of medicines for treating acute and chronic myeloid leukemia. Background technique [0002] Myeloid leukemia, including acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML), is a heterogeneous malignant hematological tumor, and it is also the most common leukemia that occurs in adults. According to data records, in 2003 alone, about 11,000 Americans were diagnosed with AML, and about 75% of them eventually died of the disease (Iovino CS and Camacho LH.2003). During the past 20 years, there have been remarkable advances in the understanding of the biology, molecular and cytogenetics of this malignancy. At the same time, great progress has been made in the treatment of AML patients. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/475A61P35/00
Inventor 陈国强朱院山宋满根
Owner RUIJIN HOSPITAL ATTACHED TO SHANGHAI NO 2 MEDICALUNIV
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