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Application of 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol to preparation of anti-tumor drug

An anti-tumor drug, the technology of peroxygen, which is applied in the field of medicine, can solve the problem that the killing effect of tumor stem cells has never been discovered.

Inactive Publication Date: 2012-11-07
GUANGDONG YUEWEI EDIBLE FUNGI TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

An ergosterol peroxide, a natural product that selectively enhances the inhibitory effect of linoleic acid on DNA polymerase beta (Mizushina Y, Watanbe I, Togashi H et al. , Biological & Pharmaceutical Bulletin, 1998, 21(5):444-8) Its structure has been reported in detail, and it has been reported in the literature that the compound has anti-inflammatory, anti-bacterial, anti-atherosclerosis and inhibitory effects on human T cell proliferation, but so far, there is no information about the chemical's ability to inhibit malignant breast cancer ( MT-1), lymphoma (Jurkat) and brain tumor (U87) cells and other anti-tumor activities have been reported, and its killing effect on drug-resistant tumor stem cells has never been found

Method used

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  • Application of 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol to preparation of anti-tumor drug
  • Application of 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol to preparation of anti-tumor drug
  • Application of 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol to preparation of anti-tumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Example 1: Isolation and purification of 5α-8α-peroxyergosta-6,22(E)-dien-3β-ol from Ganoderma lucidum spores

[0024] 1. Collect 10 kg of Ganoderma lucidum spores, break the wall by enzymatic method, and then extract by carbon dioxide supercritical extraction apparatus. The extraction conditions are: extraction pressure 25MPa±1MPa, temperature 40oC±5oC; carbon dioxide flow rate 175L / h±15L / h; separation The pressure is 6Mpa±1Mpa, the temperature of the secondary separation tank is 40 oC±2 oC, the temperature of the third separation tank is 45 oC±2 oC, and the extraction time is 4 hours; The extract, namely Ganoderma lucidum spore oil, is 1300g in total, and stored below 16°C for later use.

[0025] 2. Take 210g of Ganoderma lucidum spore oil, dissolve it with 250ml of petroleum ether (60-90), mix the sample according to the ratio of sample: silica gel = 1:2 (silica gel 160-200 mesh), according to the ratio of sample: silica gel = 1:30 Put on the column (column diameter...

Embodiment 2

[0039] Example 2: Experiment of the inhibitory effect of 5α-8α-peroxyergosta-6,22(E)-dien-3β-ol on human malignant breast tumor cells (MT-1)

[0040] 1. The 5α-8α-peroxyergosta-6,22(E)-diene-3β-alcohol obtained in Example 1 was prepared into a 10mg / ml solution with DMSO, and then diluted to 500ug / ml with DMEM medium ml of sample solution;

[0041] 2. Human malignant breast tumor cells (MT-1) in the logarithmic growth phase were treated with 0.25% trypsin, digested, and re-treated with 10% fetal bovine serum and 1% double antibody (10000U / ml penicillin + 10000U / ml ml streptomycin) suspended in DMEM medium, and then counted to prepare 2×10 5 cells / ml of cell suspension, add 0.96ml of mixed cell suspension to the 12-well plate, and store at 37°C, 5% CO 2 After culturing in the incubator for four hours, add 40ul diluted sample solution containing 5α-8α-peroxyergosta-6,22(E)-diene-3β-ol to each well, and the final concentration is 20ug / ml, set 3 repetitions for each sample solu...

Embodiment 3

[0045] Example 3: Experiment of the inhibitory effect of 5α-8α-peroxyergosta-6,22(E)-dien-3β-ol on human lymphoma cells (Jurkat)

[0046] 1. The 5α-8α-peroxyergosta-6,22(E)-diene-3β-alcohol obtained in Example 1 was prepared into a 10mg / ml solution with DMSO, and then diluted to 500ug / ml with DMEM medium ml of sample solution;

[0047] 2. Human lymphoma cells (Jurkat) in the logarithmic growth phase were treated with 0.25% trypsin, digested, and re-treated with 10% fetal bovine serum and 1% double antibody (10000U / ml penicillin + 10000U / ml streptomycin Suspended in DMEM medium, then counted and prepared into 2×10 5 cells / ml of cell suspension, add 0.96ml of mixed cell suspension to the 12-well plate, and store at 37°C, 5% CO 2 After culturing in the incubator for four hours, add 40ul diluted sample solution containing 5α-8α-peroxyergosta-6,22(E)-diene-3β-ol to each well, and the final concentration is 20ug / ml, set 3 repetitions for each sample solution, set the negative co...

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Abstract

The invention belongs to the field of medicine, and particularly relates to the application of 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol to the preparation of an anti-tumor drug. A great number of experiments show that the 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol has the remarkable effect of suppressing malignant tumors such as malignant mammary tumor cells, lymphoma cells and encephaloma cells, and particularly has the effect of killing drug-resistant tumor stem cells such as encephaloma stem cells, so that the 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol can be used for the preparation of the anti-tumor drug, and the drug contains 5alpha-8alpha-ergosterol peroxide-6,22(E)-diene-3beta-alcohol of effective content and a pharmaceutically acceptable carrier.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to the application of 5α-8α-peroxyergosta-6,22(E)-diene-3β-ol in the preparation of antitumor drugs. Background technique [0002] Malignant tumor is one of the main causes that threaten human life at present. According to data released by the World Health Organization (WHO), in 2000, the number of new cancer cases worldwide was 12.26 million, the number of cancer deaths was 7.56 million, and the cumulative risk of cancer from birth to 75 years old was 18.7% (Ferlay J et al., 2010). According to the latest data from the Ministry of Health of my country (2011), malignant tumors rank first in the cause of death in urban areas and second in rural areas, accounting for 23.66% and 19.72% of all causes of death, respectively (Ministry of Health of the People’s Republic of China, 2010). Malignant tumor control has become a health strategic priority of governments around the world. ...

Claims

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Application Information

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IPC IPC(8): A61K31/58A61P35/00
Inventor 谢意珍李向敏焦春伟罗彪潘鸿辉蔡勉华余雄涛张智
Owner GUANGDONG YUEWEI EDIBLE FUNGI TECH
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