CN101036638A - Application of glycyrrhizin in the preparation of medicine for preventing and curing tumour - Google Patents

Application of glycyrrhizin in the preparation of medicine for preventing and curing tumour Download PDF

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CN101036638A
CN101036638A CN 200610038887 CN200610038887A CN101036638A CN 101036638 A CN101036638 A CN 101036638A CN 200610038887 CN200610038887 CN 200610038887 CN 200610038887 A CN200610038887 A CN 200610038887A CN 101036638 A CN101036638 A CN 101036638A
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glycyrrhizin
cancer
cell
medicine
application
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CN101036638B (en
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蔡云清
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Nanjing University
Nanjing Medical University
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Nanjing Medical University
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Abstract

The invention relates to a medicine art, in particular relates to an application of active material glycyrrhizin from natural plant liquorice for preparing drugs for preventing and treating cancer. The drug for treating cancer is used to treat and prevent various cancers such as lung cancer, liver cancer, gastric cancer, colon cancer, etc.

Description

Glycyrrhizin is used to prevent application with the medicine for treating tumor thing in preparation
Relate to the field
The present invention relates to field of medicaments, specifically, the glycyrrhizin preparation that the present invention relates to the flavanone monomeric compound glycyrrhizin (Liquiritigenin) that will extract in the liquorice root or synthetic is used for preventing the application with the medicine for treating tumor thing.
Background technology
Since the seventies in 20th century, the cancer morbidity of China is in rising trend always, about 2,000,000 people of number of the infected of the annual cancer of present China, the number of dying from cancer surpasses 1,400,000 people, wherein, the PLC mortality rate is positioned at the 3rd of cancer mortality, has every year 110000 people to die from hepatocarcinoma, accounts for 45% of world's PLC mortality sum.China's hepatocarcinoma situation occurred frequently is very serious, and China has 1.3 hundred million HBV carriers approximately at present, and 25% virus carrier is developed into chronic hepatitis, liver cirrhosis and hepatocarcinoma the most at last.WHO expects the year two thousand twenty, and 2,000 ten thousand new cases of cancers can take place every year, and wherein great majority are in developing country.To this, the cancer that China proposes the emphasis prevention is followed successively by pulmonary carcinoma, hepatocarcinoma, gastric cancer, the esophageal carcinoma, colorectal cancer, breast carcinoma, cervical cancer and nasopharyngeal carcinoma, and their totals account for 80% of the cancer cause of the death.Face cancer challenge occurred frequently.Generation and development by the chemical cancer-resisting substance prophylaxis of cancer in the research natural plants have become a key areas of cancer chemoprophylaxis research, and are subjected to the common concern of countries in the world scientific circles.
Liquorice root is abundant in china natural resources, and Radix Glycyrrhizae has multiple pharmacological function and body-care effect, it by Ministry of Public Health list in be food be again the health food list of medicine.Radix Glycyrrhizae is important simply conventional Chinese medicine in the Chinese medicine preparation of tcm clinical practice treatment tumour patient, inquires into the important directions that the monomer component that has anti-tumor activity in the Radix Glycyrrhizae is research.Though it is not many chemical analysis persons have carried out the analysis of system from chemico-analytic angle to licorice ingredient, still comprehensive for the research of the anticancer active constituent that exists in the Radix Glycyrrhizae.Research at present thinks that triterpenes and flavone compound are the antineoplastic main active in the Radix Glycyrrhizae, wherein the research of Radix Glycyrrhizae triterpenoid compound glycyrrhizic acid and glycyrrhizin antineoplastic is more, discover as Huang Wei etc., after triterpenes monomer glycyrrhizic acid concentration was 2.5mmol/L, 5mmol/L, 10mmol/L effect hepatoma carcinoma cell 96h, cell proliferation inhibition rate was respectively 32.2%, 59.4%, 85.1% [1]And seldom, and be licoflavone class mixture, non-flavonoid monomeric compound to the research of liquorice flavonoids compound antitumaous effect.For example Fu is that force etc. discovers that licoflavone class mixture has anticancer, mutation and antioxidation, thinks that licoflavone gets a good chance of developing into the medicine of an effective prophylaxis of tumours [2]Japan Hatano discovers that licoflavone class material can cause hepatocarcinoma and the morphologic variation of mice ehrlich ascites cell on the rat abdomen [3]Glycyrrhizin belongs to the flavanone chemical compound, and research report glycyrrhizin in the past has antivirus action, have the effect for the treatment of infected by HIV and chronic hepatitis C virus as Radix Glycyrrhizae, also has the effect of anti AIDS virus [4], over the past two years, researchs such as Crance found again that glycyrrhizin can suppress duplicating of SARS associated coronavirus [5], but up to now, do not see as yet that for glycyrrhizin antitumor action and Study on Mechanism thereof report is arranged.
Summary of the invention:
Purpose of the present invention just provides in a kind of liquorice root to be extracted or the flavanone monomeric compound glycyrrhizin (Liquiritigenin) of synthetic is used for preventing and treating the application of curing oncoma medicine in preparation, described curing cancer drug be used for the treatment of and prevent hepatocarcinoma, pulmonary carcinoma, gastric cancer, colon cancer, leukemia, etc. multiple cancer.
Purpose of the present invention, advantage etc. will illustrate by the non-limitative illustration of following preferential embodiment and explain that these embodiment only provide as an example with reference to accompanying drawing.
Description of drawings
Fig. 1 is the dose-response relationship sketch map for showing glycyrrhizin 200 μ mol/L, 300 μ mol/L, 400 μ mol/L, 500 μ mol/L to the inhibition of liver cancer cell growth.
Fig. 2 is the inhibitory action sketch map of glycyrrhizin to colon cancer cell
The specific embodiment
Shown in Fig. 1, Fig. 2 and table 1, table 2, table 3, table 4, table 5, table 6, in the research process of the present invention, carried out the screening experiment of external different tumor cells, comprise human lung cancer cell A549, gastric carcinoma cells (SGC7901), human liver cancer cell (SMMC7721), human colon cancer cell (LOVO), human promyelocytic leukemia cell HL-60, through repeatedly screening, find that glycyrrhizin has the effect of obvious anticancer growth, and being dose-response relationship, PRELIMINARY RESULTS provides good basis for the further investigation of this project.
One, cell strain and screening technique
[cell strain] human lung cancer cell A549
The low differentiation of people adenocarcinoma of stomach cell BGC-823
Human liver cancer cell SMMC-7721
Human promyelocytic leukemia cell HL-60
[method]
1. get and be in one bottle in cell in good condition exponential phase of growth, add 0.25% tryptic digestive juice, digestion comes off attached cell, counting 2-4 * 10 4Individual/ml, make cell suspension.
2. obtained cell suspension is inoculated on 96 orifice plates, and 180/ hole is put in the constant temperature CO2 incubator and cultivated 24 hours.
3. change liquid, adding is subjected to the reagent thing, and cultivated 72 hours in 20/ hole.
4. MTT is added in 96 orifice plates, cultivated 4 hours in the incubator in 20/ hole.
5. inhale and remove supernatant, add DMSO, 150/ hole, jolting is 5 minutes on the dull and stereotyped shaking table.
6. measure the light absorption value in every hole with enzyme-linked immunosorbent assay instrument at wavelength 570nm place, and calculate cell inhibitory rate.
Table 1 anti-tumor activity criterion
Known molecular quantizes compound mol/L Unknown compound μ g/ml Crude extract μ g/ml Cell inhibitory rate % Active
1×10 -71×10 -61×10 -51×10 -71×10 -61×10 -51×10 -71×10 -61×10 -5 1 10 100 1 10 100 1 10 100 2 20 200 2 20 200 2 20 200 ≥50 ≥50 ≥50 <50 ≥50 ≥50 <50 <50 ≥50 +++potent ++ the weak effect of middle effect
Two, The selection result
Table 2 glycyrrhizin is to the inhibitory action of cancerous cell
Sample Final concentration μ g/ml Human liver cancer cell SMMC-7721 The human lung cancer cell A549 The low differentiation of people adenocarcinoma of stomach cell BGC-823 Human promyelocytic leukemia cell HL-6
Suppression ratio % Active Suppression ratio % Active Suppression ratio % Active Suppression ratio % Active
Glycyrrhizin 1 10 100 23.17 96.08 98.00 ++ 7.76 35.66 93.03 + 24.41 73.76 97.52 ++ 50.95 64.40 99.30 ++
Table 3 amycin is to the inhibitory action of cancerous cell
Positive drug Final concentration mol/L Human liver cancer cell SMMC-7721 The human lung cancer cell A549 The low differentiation of people adenocarcinoma of stomach cell BGC-823 Human promyelocytic leukemia cell HL-6
Suppression ratio % Suppression ratio % Suppression ratio % Suppression ratio %
Amycin 1×10 -71×10 -61×10 -5 10.28 53.40 97.47 16.42 16.42 90.44 17.86 45.80 97.67 61.59 89.73 99.09
Table 4 result shows that glycyrrhizin 250 μ mol/L, 500 μ mol/L are respectively 54.5%, 58.1% to the inhibition of stomach cancer cell.
Table 4 glycyrrhizin is to the inhibitory action (48h) of stomach cancer cell (SGC7901)
Concentration Glycyrrhizin
The OD value Suppression ratio (%)
31.25μmol/L 0.38±0.01 -22.6% **
62.5μmol/L 0.35±0.02 -12.9%
125μmol/L 0.37±0.02 -19.4% **
250μmol/L 0.14±0.01 54.8% **
500μmol/L 0.13±0.01 58.1% **
DMSO(1.5%) 0.31±0.03
ddH 2O 0.36±0.03
Compare *<0.05, * *<0.01 with DMSO
Table 5 result shows that glycyrrhizin 250 μ mol/L, 500 μ mol/L are respectively 42.0% and 89.9% to the liver cancer cell growth suppression ratio.
The present invention is through extracorporeal anti-tumor screening experiment repeatedly, the flavonoid monomeric compound glycyrrhizin (liquiritigenin) that extracts in the discovery Radix Glycyrrhizae, the SMMC7721 liver cancer cell growth had the obvious suppression effect, glycyrrhizin 200 μ mol/L, 300 μ mol/L, 500 μ mol/L effect hepatoma carcinoma cell 48h, the liver cancer cell growth suppression ratio is respectively 23.5%, 45.2%, 84.0%, and its effect that suppresses tumor is apparently higher than Radix Glycyrrhizae triterpenes monomeric compound glycyrrhizic acid.
Table 5 glycyrrhizin is to the inhibitory action (48h) of hepatoma carcinoma cell (SMMC7721)
Concentration Glycyrrhizin
OD value (570nm) Suppression ratio (%)
31.25μmol/L 1.51±0.07 -9.42% *
62.5μmol/L 1.50±0.05 -8.70% *
125μmol/L 1.47±0.06 -6.52%
250μmol/L 0.80±0.29 42.0% **
500μmol/L 0.14±0.00 89.9% **
DMSO(1.5%) 1.38±0.09
ddH 2O 1.61±0.14
Compare *<0.05, * *<0.01 with DMSO
Table 6 result shows that glycyrrhizin 125 μ mol/L, 250 μ mol/L are respectively 57.6% and 91.9% to the colon cancer cell growth inhibition ratio.
Table 6 glycyrrhizin is to LOVO (colon cancer) cell inhibiting effect (48h)
Concentration Glycyrrhizin
OD(570nm) Suppression ratio
15.62μmol/L 1.56±0.06 9.3% *
31.25μmol/L 1.53±0.03 11.0% **
62.5μmol/L 1.25±0.09 27.3% **
125μmol/L 0.73±0.05 57.6% **
250μmol/L 0.14±0.01 91.9% **
500μmol/L 0.14±0.01 91.9% **
1000μmol/L 0.12±0.00 93% **
DMSO 1.72±0.10
ddH 2O 1.92±0.10
Compare *<0.05, * *<0.01 with DMSO
3.3, conclusion
Glycyrrhizin has the effect of inhibition human liver cancer cell (SMMC7721), human lung cancer cell A549, gastric carcinoma cells (SGC7901), the low differentiation of people adenocarcinoma of stomach cell BGC-823, human colon cancer cell (LOVO), human promyelocytic leukemia cell HL-60 growth.

Claims (6)

1. the application of glycyrrhizin in preparation prevention and treatment curing cancer drug.
2. application according to claim 1, wherein said glycyrrhizin are the flavanone chemical compound.
3. application according to claim 1 and 2, wherein said curing cancer drug are used for the treatment of and prevent pulmonary carcinoma.
4. application according to claim 1 and 2, wherein said curing cancer drug are used for the treatment of and prevent hepatocarcinoma.
5. application according to claim 1 and 2, wherein said curing cancer drug are used for the treatment of and prevent gastric cancer.
6. application according to claim 1 and 2, wherein said curing cancer drug are used for the treatment of and prevent colon cancer.
CN2006100388879A 2006-03-16 2006-03-16 Application of glycyrrhizin in the preparation of medicine for preventing and curing tumour Active CN101036638B (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009031195A1 (en) * 2007-09-03 2009-03-12 Haruo Higo Composition containing flavanone compound monomer
CN103735497A (en) * 2013-12-26 2014-04-23 南京海昌中药集团有限公司 Liquiritigenin injection and preparation method and application thereof
CN104892707A (en) * 2015-06-11 2015-09-09 吉林大学 Compound CLCN based on oriented synthesis and application of CLCN to anti-liver cancer drugs
CN109715146A (en) * 2016-06-02 2019-05-03 哈佛学院校长同事会 Eradicate the method and composition of leukaemia cell

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1220518C (en) * 2002-08-26 2005-09-28 上海中耀生物科技有限公司 Chinese medicinal composition for anti-cancer and analgesia, its preparation method and its application in the preparation of product and medicine for treating cancer and analgesia

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009031195A1 (en) * 2007-09-03 2009-03-12 Haruo Higo Composition containing flavanone compound monomer
CN103735497A (en) * 2013-12-26 2014-04-23 南京海昌中药集团有限公司 Liquiritigenin injection and preparation method and application thereof
CN103735497B (en) * 2013-12-26 2016-04-20 南京海昌中药集团有限公司 Liquiritigenin injection and preparation method thereof and application
CN104892707A (en) * 2015-06-11 2015-09-09 吉林大学 Compound CLCN based on oriented synthesis and application of CLCN to anti-liver cancer drugs
CN104892707B (en) * 2015-06-11 2017-08-25 吉林大学 A kind of controlled syntheses compound CLCN and its application in medicines resistant to liver cancer
CN109715146A (en) * 2016-06-02 2019-05-03 哈佛学院校长同事会 Eradicate the method and composition of leukaemia cell
EP3463319A4 (en) * 2016-06-02 2020-02-19 President and Fellows of Harvard College Methods and compositions for eradicating leukemic cells

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