Application of Maoeryisu for pharmacy

一种毛萼乙素、药物的技术，应用在毛萼乙素领域，能够解决不能治疗急性白血病等问题

Inactive Publication Date: 2008-02-27
KUNMING INST OF BOTANY - CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the drug doesn't treat diseases like acute leukemia and Burkitt's lymphoma

Method used

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  • Application of Maoeryisu for pharmacy
  • Application of Maoeryisu for pharmacy
  • Application of Maoeryisu for pharmacy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0073] EriB inhibits growth and induces apoptosis in human leukemia cells

[0074] The effect of EriB on the growth of human hematologic malignancies was detected by MTT assay. The half-inhibition of growth of these cells by EriB was between 0.2-2 μM. Different concentrations of EriB have growth inhibitory effect on all tested cells. The half-inhibitory dose of EriB on Kasumi-1 cells was 0.2 μM, on NB4 and NB4 / R2 cells was 0.5 μM, and on NB4R1, HL60 and U937 cells was 1 μM. Malignant lymphoproliferative disorders are less sensitive to eillin than myeloid leukemia cells, IG of Raji, Daudi and Jurkat cells 50 Values ​​above 1.5 μM (see Figure 1B).

[0075] Kasumi-1 cells are the most sensitive to EriB, and EriB has a time- and dose-dependent inhibitory effect on cell growth (see Figure 1C left), and the cell survival rate also decreases correspondingly (see Figure 1C right). Inhibitory effects were also observed at concentrations below 0.25 μM. After Kasumi-1 cells were tre...

Embodiment 2

[0079] Elein B disrupts mitochondria and activates caspase-3 at apoptosis-inducing concentrations

[0080] In order to study the ultrastructural changes of Kasumi-1 cells in the early stage of apoptosis and to search for hints of mechanisms involved in apoptosis, we performed transmission microscopy analysis. Normal tumor cell nuclei were irregular in shape and contained a large number of rough endoplasmic reticulum and mitochondria (see Figure 2B), and Kasumi-1 cells treated with EriB for 6 hours showed swollen cells, increased number of lysosomes, swelling and Weakened mitochondria (see Figure 2B), suggesting early apoptosis and mitochondrial damage (see Figure 2B).

[0081] Kasumi-1 cells treated with EriB were incubated with Rhl23 and then used for flow cytometry detection. The results showed that the mitochondrial transmembrane potential decreased significantly, and there was a time and dose dependence (see FIG. 2C ). In Kasumi-1, NB4 and NB4 / R2 cells, the cleavage of ca...

Embodiment 3

[0083] Bc1-2 and Bc1-X via down-regulation of Bc1-X L Acts on intrinsic apoptotic pathway

[0084]Bcl-2 family proteins directly control the permeability of mitochondrial membranes, and they are central regulators of caspase activation. The relative members of this family, anti-apoptotic and pro-apoptotic, determine the fate of cells. In order to detect whether EriB damages mitochondria by acting on Bc1-2 family members, we used western blot and RT-PCR to detect the anti-apoptotic factors Bc1-2 and Bc1 in Kasumi-1 cells treated with EriB for 24 and 48 hours -X L And the expression of pro-apoptotic factor Bax. Bc1-2 and Bc1-X L There was a reduction at both protein and mRNA levels, however Bax expression did not change significantly (see Figure 3A and Figure 3B). Finally, EriB induces Bc1-2 / Bax and Bc1-X L Negative regulation of the / Bax ratio (see Figure 3C and Figure 3D), which is consistent with the results of disrupted mitochondrial stability during apoptosis in Kasum...

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Abstract

An application of eriocalyxin B in preparing the medicines for treating acute leukemia and Burkitt's lymphoma is disclosed.

Description

technical field [0001] The present invention relates to the use of eriocetin, in particular to the application in the field of pharmacy. Background technique [0002] Acute myeloid leukemia (AML) is a group of hematopoietic malignancies originating from abnormal proliferation, differentiation and survival of myeloid progenitor cells. Specific chromosomal translocations occur frequently in AML and play an important role in the pathogenesis of leukemia. In AML, t(8;21)(q22;q22) represents the most common chromosomal translocation that generates the AML1-ETO fusion protein. AML1-ETO blocks myeloid cell differentiation and apoptosis and is involved in leukemogenesis. Clinically, 40%-50% of t(8;21) AML patients still relapse after receiving chemotherapy and develop drug resistance. Moreover, high-dose chemotherapy drugs are not suitable for elderly patients. Therefore, it is highly desirable to develop an alternative drug that can directly target the genetic changes of this t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/352A61P35/00
CPCA61K31/352A61P35/00A61P35/02
Inventor 陈赛娟陈竺王兰赵维莅孙汉董
Owner KUNMING INST OF BOTANY - CHINESE ACAD OF SCI
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