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Anticancer application of alkaloid

An alkaloid, applied technology, applied in the field of alkaloid

Inactive Publication Date: 2012-10-10
XIAMEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] Alkaloid Exfoliazone is an alkaloid extracted from marine organisms, Kimai et al. (KIMAI S.et al., Isolation and structure of a new phenoxazine antibiotic, alkaloid Exfoliazone, produced by Streptomycesexfoliates. ): 1606-1607.) Research shows that the alkaloid Exfoliazone extracted from Streptomycesexfoliatus has antibacterial effect, and Shinsuke (Shinsuke I.et.al. alkaloid Exfoliazone and lavanducyanin, potent growth promoting substances of rat liver cell line, RLN -8, produced by streptomyces exfoliatus and streptomyces aeriouvifer [J]. J Antibiot, 1993, 46 (8): 1232-1238) showed that the alkaloid Exfoliazone had a growth-promoting effect on rat liver cell lines, but no effect on Reports on the role of cancer cells

Method used

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  • Anticancer application of alkaloid
  • Anticancer application of alkaloid
  • Anticancer application of alkaloid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 Induction of the alkaloid Exfoliazone on the expression of Nur77 in HepG2 cells

[0035] 1. Cell culture

[0036] Select liver cancer cell line HepG2 (ATCC), use DMEM medium with 10% calf serum, culture in a 6-well tissue culture plate at 37°C in a cell incubator containing 5% CO2, change the medium after 24 hours, and add after 12 hours of starvation. Drug (without serum) treatment. The alkaloid Exfoliazone was dissolved in DMSO (DMSO final concentration <0.1%) and treated with 10 μmol / L and 20 μmol / L respectively for 6 hours, the negative control group was treated with the same concentration of DMSO for 6 hours, and the positive control group was treated with phorbol ester 100 ng / mL (TPA) treatment for 3 hours, the specific treatment is as follows:

[0037] (1) Negative control group (DMSO)

[0038] (2) Positive control group (TPA)

[0039] (3) Alkaloid Exfoliazone group (10μmol / L)

[0040] (4) Alkaloid Exfoliazone group (20μmol / L)

[0041] Cells are c...

Embodiment 2

[0064] Example 2 The alkaloid Exfoliazone induces the apoptosis of liver cancer cells HepG2

[0065] 1. The growth inhibitory effect of alkaloid Exfoliazone on HepG2 cells

[0066] HepG2 cells at 5×10 3 / well seeded in 96-well plate, 5% CO 2 After culturing at 37°C for 24 hours, the alkaloid Exfoliazone was added at concentrations of 1, 10, 20, 30 and 40 μmol / L, and an equal amount of DMSO was used as the control group, and 6 replicate wells were set for each group. After drug treatment for 24, 48 and 72 hours, MTT solution (5 mg / mL, 20 μL / well) was added, and after incubation for 4 hours, DMSO (150 μL / well) was added, shaken, and developed color. The absorbance was read at a wavelength of 490nm with an enzyme-linked immunosorbent assay instrument, and the cell survival rate was calculated using the formula: cell survival rate=(average absorbance value of the experimental group / average value absorbance value of the control group)×100%. The result is as Figure 6 shown.

...

Embodiment 3

[0079] Example 3 The apoptosis of HepG2 cells induced by alkaloid Exfoliazone depends on the expression level of Nur77 and the nuclear export of Nur77

[0080] In order to study the role played by Nur77 in the apoptosis induced by alkaloid Exfoliazone, the HepG2 cells (cell culture with embodiment 2.5) after the common staining of alkaloid Exfoliazone treatment with the antibody of Nur77 and DAPI, the results are as follows Figure 10 shown.

[0081] according to Figure 10 It can be seen from the results that HepG2 cells were treated with 10 μmol / L alkaloid Exfoliazone for 24 hours. Compared with the control group, HepG2 cells did not have a significant apoptotic effect; After treating HepG2 cells for 24 hours, the apoptosis rate increased by about 60%. It shows that Nur77 mediates the apoptotic effect of the alkaloid Exfoliazone.

[0082] In order to further prove the relationship between Nur77 expression and apoptosis induction, Nur77 gene knockout MEF cells (MEF Nur77 ...

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Abstract

The invention relates to an anticancer application of an alkaloid, in particular to an alkaloid, which provides an application of the alkaloid Exfoliazone in preparing medicines for treating cancers and an application of an orphan receptor Nur77 as an action target in screening marine organism resources. The invention is characterized in that the Exfoliazone can induce the apoptosis of cancer cells, the expression of the orphan receptor Nur77 and the nuclear export of the orphan receptor Nur77; the Exfoliazone induces the nuclear export transportation of the Nur77 through a CRM1 way and finally causes the apoptosis of liver cancer cells; the apoptosis effect of the Exfoliazone depends on the nuclear export of the Nur77; the Exfoliazone is taken as a regulatory factor targeted on the apoptosis way of the Nur77 and can become an effective medicine for treating the cancers; and the medicine for treating the cancers takes the orphan receptor Nur77 as the action target.

Description

technical field [0001] The invention relates to an alkaloid, in particular to the anticancer application of an alkaloid Exfoliazone. Background technique [0002] Orphan receptor Nur77 (also known as TR3 or NGFI-B), is an important member of the nuclear receptor superfamily, it is also an immediate early gene, its expression can be controlled by serum, growth factors, myristyl phorbol acetate -13(TPA) and calcium signaling are rapidly induced (Zhang XK. et.al., Expert Opin Ther Tar 2007; 11:69-79; Moll UM, et.al., Oncogene 2006; 25:4725-4743). Nur77 was originally considered as a cell survival factor, which can mediate multiple survival signaling pathways, including protein kinase A, protein kinase C, MAPK and NF-KB pathways. The growth-promoting effect of Nur77 expression has been confirmed in a variety of tumors (Chen GQ, et.al., Int J Cancer 2002; 99:171-8; Wu Q, et.al., Carcinogenesis 2002; 23:1583-1592 ), it has been reported that the expression level of Nur77 mRNA in...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/538A61P35/00C12Q1/68C12Q1/02
Inventor 曾锦章张晓坤韦杨烨
Owner XIAMEN UNIV
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