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New mechanism research finding of glycosyl polyether compound as anti-cancer drug

A technology of compound and polyether, which is applied in the field of biomedicine, can solve the problem of the mechanism of anti-tumor activity to be studied, and achieve good anti-cancer effect and anti-proliferation effect

Inactive Publication Date: 2018-08-10
WUHAN J1 BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] However, the mechanism of action of polyether antibiotics to exert antitumor activity remains to be studied.

Method used

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  • New mechanism research finding of glycosyl polyether compound as anti-cancer drug
  • New mechanism research finding of glycosyl polyether compound as anti-cancer drug
  • New mechanism research finding of glycosyl polyether compound as anti-cancer drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] The preparation method of embodiment 1 polyether compound

[0039] One Streptomyces nanchangensis subtype, two Streptomyces hygroscopicus subtypes and one Streptomyces endus subtype Streptomyces were inoculated on the SFM plate, and cultured for about three to four days. When colonies are formed in the SFM medium, pick a single colony and culture it in the seed medium for about three to four days, and inoculate it into the fermentation medium according to 1% amount (the composition of the fermentation medium is 30g / L of soluble starch, yellow Bean cake powder 10g / L, yeast extract 2.5g / L, CaCO 3 3g / L, pH 7.2). Culture conditions: 30 degrees, 220 rotation speed, culture for 7 to 8 days.

[0040] When the culture reaches the 7th or 8th day, collect the fermentation broth and centrifuge at a high speed to separate the supernatant from the mycelium, add an equal amount of acetone to the mycelium to destroy the bacteria, ultrasonicate for 20 minutes, spin evaporate acetone...

Embodiment 2

[0046] Example 2 Research on J1001-2 Sodium Salt by Proteomics and Phosphoproteomics

[0047] (1) Cell culture

[0048] MDA-MB-231 cells (triple-negative breast cancer cells) were cultured with DEME containing 10% fetal bovine serum, 80 μg / mL streptomycin, and 80 U / mL penicillin at 37°C and 5% CO 2 Routine cultivation in an incubator. When the cells are about 90% full, add the drug J1001-2 sodium salt. In the protein group experiment, 4 drug administration groups (administration concentration of 2 μM) were set up, which were 24h, 48h, 72h and blank group (no drug addition). In the phosphorylated protein group experiment, two administration groups (administration concentration of 3 μM) were set up for 6h, 12h and a blank group (no drug addition).

[0049] (2) Experimental methods of proteomics

[0050] 1) Proteome sample preparation

[0051] Collect the cells of the blank group and the administration group, transfer to a 1.5mL centrifuge tube, centrifuge at 2500rpm at 4°C ...

Embodiment 3

[0061] Example 3 Polyether compounds cause tumor cell reactive oxygen species (ROS) to increase

[0062] 1. Experimental method

[0063] MDA-MB-231 cells (triple-negative breast cancer cells) were cultured with DEME containing 10% fetal bovine serum, 80 μg / mL streptomycin, and 80 U / mL penicillin at 37°C and 5% CO 2 Routine cultivation in an incubator. When the cells are about 80% full, add the drug J1001-1 or J1001-2. The stock solution concentration of the drug is 50 mg / mL, and the drug is diluted to the set drug concentration with PBS. In the drug administration group, two drug concentrations (1 μM and 4 μM) are set, and the blank group (no drug added). Drug action time is 16 hours, repeated three times. Biyuntian active oxygen detection kit was used to detect according to the experimental steps provided by the kit, and the fluorescence intensity of the blank group and the drug-administered group was detected by flow cytometry to obtain Figure 7 The data.

[0064] 2. R...

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Abstract

The invention discloses researches on mechanism of action of polyether compounds in anti-tumor. The drug is used for acting on at least one of the following signal pathways through induced apoptosis by affecting calcium, mediated apoptosis by affecting intracellular reactive oxygen species (ROS) level and mediated apoptosis by affecting cytochrome C level of cell mitochondria. The polyether compounds can cause death of tumor cells through controlling multiple signal pathways, and thus, the anticancer effects can be better achieved.

Description

technical field [0001] The invention relates to the field of biomedicine. Specifically, the present invention relates to the discovery of new mechanisms of polyether compounds as anticancer drugs. Background technique [0002] Polyether antibiotics are an important class of type I polyketides produced by Streptomyces. Currently, they are mainly used as veterinary drugs to prevent coccidiosis in animals and improve feed utilization to promote growth, such as: salinomycin, lasalocid , nigericin and maduramycin. Up to now, more than 120 kinds of polyether compounds have been found and reported. The polyether compound carrier has chelated metal cations (Na + 、K + , Ca 2+ ), the ability to form a fat-soluble complex, the carrier can diffuse from the outside to the inside of the cell, and return to the outside of the cell or stay on the cell membrane as a metal ion transport carrier to and from the inside and outside of the cell, promoting the transmembrane transfer of metal i...

Claims

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Application Information

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IPC IPC(8): A61K31/351A61P35/00
CPCA61K31/351
Inventor 刘天罡黄敏坚刘然
Owner WUHAN J1 BIOTECH
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