Application of artemisia apiacea derivative in preparation of anti-cancer drugs

Abstract

The invention provides application of an artemisia apiacea derivative in preparation of an anti-cancer drug. The artemisia apiacea derivative is artemisinene. The research finds that the artemisia apiacea derivative shows relatively strong anti-cancer activity on tumor cells, can induce death of cancer cells, is a potential anti-cancer drug, and has a good application prospect in the field of cancer treatment.

Description

Technical Field

[0001] The present invention relates to the field of biomedicine technology, and in particular to the use of an artemisia annua derivative in the preparation of an anticancer drug. Background Art

[0003] For cancer treatment, there are now surgery, chemotherapy, radiotherapy, immunotherapy, traditional Chinese medicine and other means of treatment. Western medicine has serious side effects and is harmful to the human body. my country has a long history of using traditional Chinese medicine, and traditional Chinese medicine has few side effects. Therefore, it is necessary to study small molecule drugs of traditional Chinese medicine for cancer treatment.

[0004] Artemisinene is a sesquiterpenoid compound extracted from Artemisia annua. As a precursor of the antimalarial drug artemisinin, it has important drug development value. Artemisinene is insoluble in water but soluble in organic solvents. Studies in recent years have shown that Artemisia annua derivatives also show potential application prospects in the fields of anti-tumor, anti-inflammatory and immunomodulation. At present, there are no reports on the anti-cancer activity of artemisinene. Summary of the invention

[0005] In view of the above-mentioned shortcomings of the prior art, the purpose of the present invention is to provide a use of an Artemisia annua derivative in the preparation of an anticancer drug. The Artemisia annua derivative exhibits strong anticancer activity against tumor cells and can induce cancer cell death. It is a potential anticancer drug with good application prospects in the field of cancer treatment.

[0006] To achieve the above-mentioned purpose and other related purposes, the present invention provides a use of an Artemisia annua derivative in the preparation of an anticancer drug, wherein the Artemisia annua derivative is artemisinene.

[0007] Artemisinin is a sesquiterpenoid compound extracted from the aerial parts of the Asteraceae plant Artemisia annua. It is a precursor molecule of artemisinin and is a colorless or light yellow solid at room temperature. The structural formula of artemisinin is as follows: .

[0008] After extensive research and experiments, the present application found that artemisinin can play a role in cancer treatment and can be used to prepare anticancer drugs.

[0009] Preferably, the anticancer drug is a drug used to prevent and / or treat cancer.

[0010] Preferably, the dosage form of the anticancer drug is any one of compressed tablets, dispersible tablets, enteric-coated tablets, capsules, granules, pellets, emulsions, powders, oral solutions and injections.

[0011] Preferably, the anticancer drug is one of an anti-pancreatic cancer drug, an anti-non-small cell lung cancer drug, an anti-glioma drug, an anti-esophageal cancer drug, an anti-liver cancer drug, an anti-small cell lung cancer drug, an anti-prostate cancer drug, an anti-bladder cancer drug, an anti-colorectal cancer drug, an anti-breast cancer drug and an anti-ovarian cancer drug.

[0012] The present invention also provides an anticancer drug, which contains 15-480 μM artemisinin.

[0013] Preferably, the anticancer drug is an anti-liver cancer drug, and the anti-liver cancer drug contains 25-200 μM artemisinin.

[0014] Preferably, the anticancer drug is one of an anti-pancreatic cancer drug, an anti-ovarian cancer drug and an anti-non-small cell lung cancer drug, and the anticancer drug contains 10-70 μM artemisinin.

[0015] Preferably, the anticancer drug is an anti-esophageal cancer drug, an anti-glioma drug, an anti-colorectal cancer drug and an anti-small cell lung cancer drug, and the anticancer drug contains 10-130 μM artemisinin.

[0016] Preferably, the anticancer drug is an anti-breast cancer drug, and the anticancer drug contains 30-480 μM artemisinin.

[0017] As described above, the present invention has the following beneficial effects: the artemisia annua derivatives exhibit strong anticancer activity against tumor cells and can induce cancer cell death, and are potential anticancer drugs with good application prospects in the field of cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of liver cancer cells LM3, G2, and Huh1.

[0019] Figure 2 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of small cell lung cancer cells H446.

[0020] Figure 3 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of prostate cancer cells PC3 and C4-2.

[0021] Figure 4 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of bladder cancer cell C24.

[0022] Figure 5 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of pancreatic cancer cells PANC-1, SW1990, and CAPAN-2.

[0023] Figure 6 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of non-small cell lung cancer cells H460, H1299, and A549.

[0024] Figure 7 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of brain glioma cells CT2A and GL261.

[0025] Figure 8 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of esophageal cancer cells KYSE70 and TE1.

[0026] Fig. 9 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of colorectal cancer cells HCT116, HT29, and LoVo.

[0027] Fig.10 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of ovarian cancer cell A2780.

[0028] Fig.11 This is the result of using CCK8 method to detect the effect of artemisinin on the growth and proliferation of breast cancer cells MDA-MB231, SUM149PT, and KPL-4. DETAILED DESCRIPTION

[0029] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0030] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified in the present invention, both endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meaning as those generally understood by those skilled in the art. In addition to the specific methods, equipment, and materials used in the embodiments, according to the grasp of the prior art by those skilled in the art and the record of the present invention, any methods, equipment, and materials of the prior art similar or equivalent to the methods, equipment, and materials described in the embodiments of the present invention can also be used to realize the present invention.

[0031] Unless otherwise stated, the experimental methods, detection methods, and preparation methods disclosed in the present invention all adopt conventional techniques in the field of molecular biology, biochemistry, chromatin structure and analysis, analytical chemistry, cell culture, recombinant DNA technology, and related fields.

[0032] The following one or more pharmaceutically acceptable excipients refer to pharmaceutically acceptable carriers or excipients, such as conventional diluents (water, etc.), fillers (lactose, etc.), binders (starch, dextrin, etc.), transdermal absorption enhancers, flavoring agents, thickeners, solubilizers (ethanol, etc.) and other excipients.

[0033] The following external preparations include ointments, creams, gels, coatings, patches, tinctures, aerosols, etc.; the following oral preparations include tablets, granules, capsules, pills, powders, oral liquids, syrups, etc.

[0034] Sources of reagents used in the following examples of this application: Artemisinin was purchased from Shanghai Yuanye Biotechnology Co., Ltd. (CAS No.: 101020-89-7).

[0035] Cell Counting Kit 8 (CCK8) was used to detect the effect of artemisinin on cell proliferation (1) Select cancer cells that are in good growth condition and in the logarithmic growth phase (see Table 1 for specific cell names), digest them with 0.25% trypsin in 0.02% EDTA, and terminate the digestion by adding the corresponding complete medium containing 10% FBS. After pipetting into a cell suspension, transfer to an EP tube, centrifuge at 800 rpm for 5 min, discard the supernatant, and add 5A complete medium to make a cell suspension; (2) Count the cells using a cell counting plate. Inoculate 4,000 cells in a 96-well plate with 5 replicate wells per group of cells at a volume of 100 μL per well. Add an equal amount of phosphate buffered saline (PBS solution) to the wells around the edges to prevent edge effects. (3) Incubate the cells in a 37°C, 5% CO2 incubator overnight with conventional culture medium. Remove the liquid culture medium from each well and add the drug of the corresponding concentration prepared under light-proof conditions to the wells for continued culture. (4) After 24 h of incubation, remove the culture medium from the plate in a dark environment, prepare the CCK8 solution required for the experiment, add 100 μL of solution to each well (prevent bubbles from forming during the addition process to avoid inaccurate measurement by the microplate reader), and incubate in the incubator for 1-2 h. (5) Adjust the wavelength of the automatic microplate reader to 450 nm and measure the OD value of each well; (6) The growth curve of each group of cells was drawn according to the OD value, and Graphpad 8.0 was used to calculate and analyze the cell proliferation.

[0036] Table 1. Dosage of artemisinin in different cancer cells Figure 1-11This is a graph showing the results of using the CCK8 method to detect the effect of artemisinin on the growth and proliferation of different cancers in this example.

[0037] like Figure 1 As shown in Figure 2, artemisinin has a significant effect on the survival rate of liver cancer cells LM3, G2, and Huh1. 50 They are 42.6 μM, 32.12 μM and 19.74 μM respectively.

[0038] like Figure 2 As shown in Figure 2, artemisinin has a significant effect on the survival rate of small cell lung cancer cells H446. 50 It is 0.9752μM.

[0039] like Figure 3 As shown in Figure 2, artemisinin has a significant effect on the survival rate of prostate cancer cells PC3 and C4-2. 50 6.384μM and 3.84μM respectively.

[0040] like Figure 4 As shown in Figure 2, artemisinin has a significant effect on the survival rate of bladder cancer cell C24. 50 It is 3.733μM.

[0041] like Figure 5 As shown in Figure 2, artemisinin has a significant effect on the survival rate of pancreatic cancer cells PANC-1, SW1990, and CAPAN-2. 50 They are 25.69μM, 22.72μM and 12.8μM respectively.

[0042] like Figure 6 As shown in Figure 2, artemisinin has a significant effect on the survival rate of non-small cell lung cancer cells H460, H1299, and A549. 50 They are 6.542μM, 9.49μM and 8.012μM respectively.

[0043] like Figure 7 As shown in Figure 2, artemisinin has a significant effect on the survival rate of brain glioma cells CT2A and GL261. 50 They are 6.124μM and 8.355μM respectively.

[0044] like Figure 8 As shown in Figure 2, artemisinin has a significant effect on the survival rate of esophageal cancer cells KYSE70 and TE1. 50 13μM and 11.59μM respectively.

[0045] like Fig. 9 As shown in Figure 2, artemisinin has a significant effect on the survival rate of colorectal cancer cells HCT116, HT29, and LoVo. 50They are 4.073μM, 14.03μM and 27.84μM respectively.

[0046] like Fig.10 As shown in Figure 2, artemisinin has a significant effect on the survival rate of ovarian cancer cell A2780. 50 It is 5.219μM.

[0047] like Fig.11 As shown in Figure 2, artemisinin has a significant effect on the survival rate of breast cancer cells MDA-MB231, SUM149PT, and KPL-4. 50 They are 15.94μM, 30.25μM and 11.87μM respectively.

[0048] The present application also provides an anticancer drug, comprising the anticancer drug as described above and a pharmaceutically acceptable excipient. The dosage form of the preparation is not limited, for example, it can be a tablet, a pill, a capsule, a granule, etc.

[0049] In summary, the present invention has found that the artemisia annua derivatives exhibit strong anticancer activity against tumor cells and can induce cancer cell death, and are potential anticancer drugs with good application prospects in the field of cancer treatment. Therefore, the present invention effectively overcomes the various shortcomings of the prior art and has a high industrial utilization value.

[0050] The above embodiments are merely illustrative of the principles and effects of the present invention, and are not intended to limit the present invention. Anyone familiar with the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by a person of ordinary skill in the art without departing from the spirit and technical concept disclosed by the present invention shall still be covered by the claims of the present invention.

Claims

1. Use of an Artemisia annua derivative in the preparation of an anticancer drug, characterized in that: The artemisia annua derivative is artemisinene.

2. The use according to claim 1, characterized in that: The anticancer drug is a drug used to prevent and / or treat cancer.

3. The use according to claim 1, characterized in that: The dosage form of the anticancer drug is any one of compressed tablets, dispersible tablets, enteric-coated tablets, capsules, granules, pellets, emulsions, powders, oral solutions and injections.

4. The use according to claim 1, characterized in that: The anticancer drug is one of anti-pancreatic cancer drugs, anti-non-small cell lung cancer drugs, anti-glioma drugs, anti-esophageal cancer drugs, anti-liver cancer drugs, anti-small cell lung cancer drugs, anti-prostate cancer drugs, anti-bladder cancer drugs, anti-colorectal cancer drugs, anti-breast cancer drugs and anti-ovarian cancer drugs.

5. An anticancer drug, characterized in that: Contains 15~480μM artemisinin.

6. The anticancer drug according to claim 5, characterized in that: The anticancer drug is an anti-liver cancer drug, and the anti-liver cancer drug contains 25-200 μM artemisinin.

7. The anticancer drug according to claim 5, characterized in that: The anticancer drug is one of an anti-small cell lung cancer drug, an anti-prostate cancer drug and an anti-bladder cancer drug, and the anticancer drug contains 20-100 μM artemisinin.

8. The anticancer drug according to claim 5, characterized in that: The anticancer drug is one of an anti-pancreatic cancer drug, an anti-ovarian cancer drug and an anti-non-small cell lung cancer drug, and the anticancer drug contains 10-70 μM artemisinin.

9. The anticancer drug according to claim 5, characterized in that: The anticancer drugs are anti-esophageal cancer drugs, anti-glioma drugs, anti-colorectal cancer drugs and anti-small cell lung cancer drugs, and the anticancer drugs contain 10-130 μM artemisinin.

10. The anticancer drug according to claim 5, characterized in that: The anticancer drug is an anti-breast cancer drug, and contains 30-480 μM artemisinin.

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