CN112190579A - Application of scoparone in tumor treatment medicine and tumor treatment medicine - Google Patents

Application of scoparone in tumor treatment medicine and tumor treatment medicine Download PDF

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Publication number
CN112190579A
CN112190579A CN202011245981.8A CN202011245981A CN112190579A CN 112190579 A CN112190579 A CN 112190579A CN 202011245981 A CN202011245981 A CN 202011245981A CN 112190579 A CN112190579 A CN 112190579A
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scoparone
medicine
application
tumor
apoptosis
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张丝雨
杨卫兵
周琼
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Tongji Medical College of Huazhong University of Science and Technology
Union Hospital Tongji Medical College Huazhong University of Science and Technology
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Union Hospital Tongji Medical College Huazhong University of Science and Technology
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Priority to CN202011245981.8A priority Critical patent/CN112190579A/en
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Priority to CN202110617960.2A priority patent/CN113368104A/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/282—Artemisia, e.g. wormwood or sagebrush
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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Abstract

The invention belongs to the research field of scoparone, and particularly discloses application of scoparone in a medicine for treating tumors and a medicine for treating tumors. The application of the scoparone in preparing the medicine for treating the tumor is the application of the scoparone in preparing the medicine for inhibiting the proliferation of the tumor cells, the application of the scoparone in preparing the medicine for promoting the apoptosis of the tumor cells and the application of the scoparone in preparing the medicine for treating the tumor as an effective component for activating a p53 signal channel; a medicine for inhibiting tumor cell proliferation and promoting tumor cell apoptosis comprises scoparone; a medicine for activating p53 signal pathway to inhibit tumor cell proliferation and promote apoptosis contains scoparone. The beneficial effects are that: the scoparone activates a p53 signal channel by inducing DNA damage, inhibits the proliferation of tumor cells, retards the progress of the cell cycle and promotes the apoptosis of the cells.

Description

Application of scoparone in tumor treatment medicine and tumor treatment medicine
Technical Field
The invention belongs to the research field of scoparone, and particularly relates to application of scoparone in a medicine for treating tumors and a medicine for treating tumors.
Background
Herbal artemisia capillaris is traditionally used in traditional Chinese medicine for treating jaundice and other diseasesLiver and gallbladder diseases. The research finds that the artemisia capillaris also plays an important role in diabetes and lipid metabolism diseases. Therefore, scoparone has received attention from many researchers as a major extract of artemisia capillaris. Scoparone is a medicine with effects of lowering blood pressure, promoting bile flow, resisting inflammation, relieving pain, reducing blood lipid, relieving asthma, and resisting coagulation, and has molecular formula C11H10O4。
Presently, scoparone exerts an anti-inflammatory effect mainly in the treatment of hepatitis, osteoarthritis and heart diseases. In recent years, some studies find that scoparone has toxic effect on colorectal cancer cells and prostate cancer cells, but the effect on lung cancer cells is not reported.
Disclosure of Invention
Aiming at the problems, the invention provides the application of scoparone in a medicine for treating tumors, mainly provides a new treatment mode for tumors, and also provides a new application approach for scoparone.
In order to solve the problems, the invention adopts the following technical scheme:
application of scoparone in preparing medicine for treating tumor is provided.
In some embodiments, the application is the application of scoparone in preparing a medicament for inhibiting tumor cell proliferation.
In some embodiments, the application is the application of scoparone in preparing a medicine for promoting tumor cell apoptosis.
In some embodiments, the application of scoparone as an effective component for activating a p53 signal pathway in preparing a medicament for treating tumors.
In some embodiments, the application is the application of scoparone as an effective component for inducing DNA damage and activating a p53 signal pathway in preparing a medicine for treating tumors.
In some embodiments, the neoplastic disease is lung cancer.
A medicine for treating tumor comprises scoparone.
In some embodiments, scoparone is an effective component for activating the p53 signaling pathway.
In some embodiments, scoparone is an effective component for inhibiting tumor cell proliferation and promoting tumor cell apoptosis by activating the p53 signal pathway.
In some embodiments, scoparone is an effective component for inducing DNA damage and activating the p53 signaling pathway.
A medicine for inhibiting tumor cell proliferation and promoting tumor cell apoptosis contains scoparone.
A medicine for activating p53 signal pathway to inhibit tumor cell proliferation and promote apoptosis contains scoparone.
A medicine for inducing DNA damage to activate p53 signal channel to inhibit tumor cell proliferation and promote apoptosis contains scoparone.
The invention has the beneficial effects that:
the scoparone activates a p53 signal channel by inducing DNA damage, inhibits the proliferation of tumor cells, retards the progress of the cell cycle and promotes the apoptosis of the cells.
Drawings
FIG. 1 shows the result of proliferation experiment of scoparone CCK 8;
FIG. 2 shows the results of EdU immunofluorescence experiments;
FIG. 3 is a graph showing the results of detecting apoptosis by flow cytometry;
FIG. 4 is a graph of the results of a TUNEL experiment;
FIG. 5 is a graph showing the results of WesternBlot detecting the expression of phosphorylated H2A.X (γ -H2A.X) protein, which is a DNA damage-related molecule;
FIG. 6 is a graph of the transcriptome sequencing results;
FIG. 7 is a graph showing the results of a cell cycle assay;
FIG. 8 is a graph showing the results of examining the expression of p53 protein in a WesternBlot western blot experiment.
Detailed Description
The following is further described in conjunction with the detailed description:
application of scoparone in preparing medicine for treating tumor is provided.
The application is the application of scoparone in preparing a medicine for inhibiting tumor cell proliferation.
The application is the application of scoparone in preparing a medicine for promoting tumor cell apoptosis.
Application of scoparone as an effective component for activating a p53 signal channel in preparation of a medicament for treating tumors.
The application is the application of the scoparone as an effective component for inducing DNA damage and activating a p53 signal path in the preparation of a medicine for treating tumors.
The tumor diseases include malignant tumor diseases, such as lung cancer, adenocarcinoma, etc.
A medicine for treating tumor comprises scoparone.
Scoparone is an effective component for activating a p53 signal channel.
The scoparone lactone is an effective component for inhibiting the proliferation of tumor cells and promoting the apoptosis of the tumor cells by activating a p53 signal path.
The scoparone lactone is an effective component for inducing DNA damage of tumor cells and activating a p53 signal channel.
The medicine for inhibiting tumor cell proliferation and promoting tumor cell apoptosis contains scoparone as effective component for inhibiting tumor cell proliferation and promoting tumor cell apoptosis, and the medicine is compounded with other supplementary material.
A medicine for activating p53 signal pathway to inhibit tumor cell proliferation and promote apoptosis contains scoparone.
A medicine for inducing the DNA damage of tumor cells (non-small cell lung cancer cells) to activate p53 signal channel to suppress the proliferation of tumor cells and promote their apoptosis contains scoparone, which is used as the component for directly inducing the DNA damage of tumor cells to activate p53 signal channel to suppress the proliferation of tumor cells and promote their apoptosis.
Example 1CCK8 method for detecting cell proliferation
A549 cells were treated with different concentrations of scoparone (0.25mM, 0.5mM, 0.75mM) in DMSO as solvent for 24 hr, and the treated A549 cells were collected as a control group, centrifuged with 0.25% trypsin, and inoculated with 3X 103The cells were plated in 96-well plates at 37 ℃ with 5% CO2Culturing in incubator, each group has 6 complex holesAfter culturing for 96h, adding cell culture solution containing 10 mul CCK8 working solution into each well, culturing for 2h in a cell culture box, measuring the light absorption value (A450) under 450nm of a microplate reader, and drawing a CCK8 curve chart. As shown in FIG. 1, the results show that the OD value decreases with the increase of the scoparone concentration.
Example 2EdU proliferation assay
A549 cells were plated at 3X 10 per well4Inoculating each cell in a 24-well plate, and adding scoparone to treat for 24h after the cells adhere to the wall. Adding 200 μ L cell fixing solution (PBS containing 4% paraformaldehyde) into 24-well plate, incubating at room temperature for 30min, adding 200 μ L glycine (2mg/mL), decolorizing and incubating by shaking table for 5min, adding 500 μ L PBS into 24-well plate, decolorizing and incubating by shaking table for 10min, adding 200 μ L penetrant (0.5% TritonX-100 PBS) into 24-well plate, and decolorizing by shaking table; washing with PBS, adding 200 μ LApollo staining reaction solution into 24-well plate, decolorizing at normal temperature in dark place with shaking table, and incubating for 30min to obtain waste solution; and respectively adding 200 mu L of penetrant into a 24-pore plate, washing with PBS for 2-3 times, and decoloring by a shaking table according to the proportion of HOECHEST: PBS (1: 1000) was stained with 200. mu.L of PBS per well, and washed with PBS; photographs were taken under a confocal microscope. The inhibition of the scoparone on the proliferation of A549 is reflected (figure 2), and the number of the cells which are positive to the A549 EdU of the scoparone treated by 0.5mM is obviously less than that of the control group.
Example 3TUNEL staining
Inoculating the cells after drug treatment on a cell slide, preparing TUNEL detection solution according to the requirements of a kit, dripping a proper amount of detection solution on the slide, incubating at 37 ℃ for 60min, washing with PBS for 3 times, and washing for 5min each time; and finally, dripping an anti-fluorescence quenching agent containing DAPI, and observing under a laser confocal microscope. In the TUNEL experiment (fig. 4), the scoparone treated group was positive for TUNEL fluorescence, indicating that tumor cell DNA was fragmented.
Example 4WesternBlot assay protein expression
Adding protein lysate into human lung cancer cell A549 treated by 1% DMSO or scoparone to collect cell protein sample, quantifying, taking an equal amount of protein sample, performing SDS-PAGE electrophoretic separation, transferring membrane, sealing with 5% skimmed milk powder for 1h, adding gamma-H2A.X, H2A.X, p53 or GAPDH antibody, and incubating overnight at 4 ℃. And adding a secondary antibody marked by HRP after washing, incubating for 1h at room temperature, adding a chemiluminescent liquid after washing for color development, and taking a picture. The expression of phosphorylated H2A.X (gamma-H2A.X) protein which is related to DNA double-strand damage is detected by a Western Blot technology (figure 5), and the expression content of the gamma-H2A.X protein is increased along with the increase of the concentration of scoparone.
Example 5 flow cytometry detection of apoptosis and cell cycle
In an apoptosis experiment, the treated cells are washed once by PBS, Annexin V and PI reagents are added according to the specification of an Annexin V/PI apoptosis detection kit, and the cells are subjected to computer detection after being incubated for 30min at room temperature in a dark place. Apoptosis experimental data were analyzed using Flow Jo software. In order to detect the cell cycle, the cells washed by PBS are fixed with 70% glacial ethanol overnight, washed by PBS, added with PI-RNaseA reagent, incubated at room temperature in the dark for 30min, and then tested on the computer, and the cycle data is analyzed by ModFit software. Using flow cytometry (figure 3) it was found that scoparone promoted apoptosis of a549 cells in a concentration-dependent manner. In the cell cycle detection experiment (fig. 7), the proportion of G1 phase of the scoparone treated cells is obviously increased, which indicates that the cells are blocked at the G1 phase.
Example 6 transcriptome sequencing
The Trizol method is used for extracting RNA of A549 cells treated by 1% DMSO or scoparone. First, a transcriptome library was prepared and machine sequenced. And then screening differential genes in different groups, carrying out clustering analysis, volcano graph visualization display and the like on the differential genes, and carrying out GO/KEGG function annotation and function enrichment analysis on the differential genes. Transcriptome sequencing (fig. 6) results showed that scoparone exerts an inhibitory effect on a549 cells by activating the p53 signaling pathway, and the expression of p53 protein was verified in Western blot protein immunoblotting experiments (fig. 8).
It will be apparent to those skilled in the art that various modifications may be made to the above embodiments without departing from the general spirit and concept of the invention. All falling within the scope of protection of the present invention. The protection scheme of the invention is subject to the appended claims.

Claims (13)

1. Application of scoparone in preparing medicine for treating tumor is provided.
2. Use according to claim 1, characterized in that: the application is the application of scoparone in preparing a medicine for inhibiting tumor cell proliferation.
3. Use according to claim 1, characterized in that: the application is the application of scoparone in preparing a medicine for promoting tumor cell apoptosis.
4. Use according to claim 1, characterized in that: application of scoparone as an effective component for activating a p53 signal channel in preparation of a medicament for treating tumors.
5. Use according to claim 4, characterized in that: the application is the application of the scoparone as an effective component for inducing DNA damage and activating a p53 signal path in the preparation of a medicine for treating tumors.
6. Use according to any one of claims 1 to 5, characterized in that: the tumor disease is lung cancer.
7. The medicine for treating the tumor is characterized in that: comprises scoparone.
8. The agent for treating tumor according to claim 7, wherein: scoparone is an effective component for activating a p53 signal channel.
9. The agent for treating tumor according to claim 8, wherein: the scoparone lactone is an effective component for inhibiting the proliferation of tumor cells and promoting the apoptosis of the tumor cells by activating a p53 signal path.
10. The agent for treating tumors according to claim 9, characterized in that: the scoparone lactone is an effective component for inducing DNA damage of tumor cells and activating a p53 signal channel.
11. The medicine for inhibiting the proliferation of tumor cells and promoting the apoptosis of the tumor cells is characterized in that: comprises scoparone.
12. A medicine for inhibiting tumor cell proliferation and promoting apoptosis by activating a p53 signal path, which is characterized in that: comprises scoparone.
13. The medicine for inducing the DNA damage of the tumor cells to activate the p53 signal path to inhibit the proliferation of the tumor cells and promote the apoptosis is characterized in that: comprises scoparone.
CN202011245981.8A 2020-11-10 2020-11-10 Application of scoparone in tumor treatment medicine and tumor treatment medicine Pending CN112190579A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015072734A1 (en) * 2013-11-13 2015-05-21 주식회사 케이스템셀 Composition for preventing or treating osteoporosis, containing extract containing artemisia capillaris-derived scoparone as active ingredient

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Publication number Priority date Publication date Assignee Title
KR101093930B1 (en) * 2007-09-13 2011-12-13 경북대학교병원 Novel use of scoparone

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015072734A1 (en) * 2013-11-13 2015-05-21 주식회사 케이스템셀 Composition for preventing or treating osteoporosis, containing extract containing artemisia capillaris-derived scoparone as active ingredient

Non-Patent Citations (2)

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Title
蒋幼凡等: "菌陈素对肺癌细胞增殖和细胞周期的影响", 《中国药业》 *
谭永忠等: "茵陈素对肺癌细胞增殖和细胞周期的影响", 《中国药房》 *

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Application publication date: 20210108