KR20170095416A - A pharmaceutical comprising rosmarinic acid for treating of preventing colorectal cancer - Google Patents
A pharmaceutical comprising rosmarinic acid for treating of preventing colorectal cancer Download PDFInfo
- Publication number
- KR20170095416A KR20170095416A KR1020160010197A KR20160010197A KR20170095416A KR 20170095416 A KR20170095416 A KR 20170095416A KR 1020160010197 A KR1020160010197 A KR 1020160010197A KR 20160010197 A KR20160010197 A KR 20160010197A KR 20170095416 A KR20170095416 A KR 20170095416A
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- KR
- South Korea
- Prior art keywords
- colorectal cancer
- rosmarinic acid
- cells
- treating
- metastatic colorectal
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- A—HUMAN NECESSITIES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
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Abstract
Description
The present invention relates to a pharmaceutical composition containing ROSMARINIC ACID as an active ingredient for preventing, ameliorating or treating colorectal cancer.
The composition according to the present invention has a feature of preventing, ameliorating or treating colon cancer through CT26 cell, which is a mouse-derived metastatic colorectal cancer cell line, through the effect of inducing apoptosis and regulating cell cycle.
The composition according to the present invention has the characteristic of improving or treating the metastasis of colon cancer through the efficacy of inhibiting the metastatic ability of colon cancer by controlling the epithelial-mesodermal conversion factor, the mobility / invasiveness factor and the AMPKa activator.
Colon cancer is a malignant tumor composed of cancer cells in the large intestine. It causes symptoms such as change in bowel habits, diarrhea, constipation, stool, abdominal pain, abdominal distension, fatigue, anorexia or indigestion.
Causes of colorectal cancer can be divided into genetic or environmental factors. Among the environmental factors, changes in Western eating habits (excessive fat intake, fiber and calcium deficiency) and lack of exercise were found to be the most common causes.
According to data from the Central Cancer Registry, 224,177 cancer cases occurred in Korea in 2012, among which 28,988 cases of men and women were combined, accounting for 12.9% of the total, which is the third most common cancer. Therefore, in the country, men and women over the age of 50 are required to have a fecal occult blood test once a year.
For the treatment of colorectal cancer, the treatment method is decided according to the degree of tissue penetration of cancer cells. In primary cancer, most cases are resection, chemotherapy or radiation therapy. However, as a side effect of surgery, postoperative complications such as pulmonary complication, anastomotic leakage, hemorrhage or intestinal obstruction may occur.
Side effects of chemotherapy include leukocytosis, thrombocytopenia, hair loss, nausea (nausea, nausea), vomiting and fatigue. Side effects of radiation therapy include pelvic pain, changes in bowel habits, dysuria, anal pain, diarrhea Or hair loss is known.
In addition, colorectal cancer recurs in about 20-50% of cases even after radical resection. Local recurrence, distant metastasis, and recurrence with local recurrence and distant metastasis appear. In general, a wide range of recurrences is associated with local recurrence and distant metastasis. In the case of metastatic colon cancer, the disease is classified as the most advanced stage and its prognosis is poor.
Therefore, it is necessary to develop new therapeutic potentials for the prevention and treatment of metastatic cancer, which is difficult to perform and has poor prognosis, while complementing current treatments with many side effects.
On the other hand, the present inventors paid attention to rosmarinic acid (ROSMARINIC ACID), which is a phenolic compound, and is known to be contained in various kinds of foods and herbal medicines. Rosmarinic acid has been reported to have antimicrobial, anti-inflammatory and antioxidant activity, and recently it has been reported to be effective in preventing dementia through cranial nerve protection. In addition, the effect of rosmarinic acid on the inhibition of metastasis of breast cancer and stomach cancer has been reported.
However, no studies have been conducted on the prevention, improvement or treatment of colorectal cancer. In particular, the mechanism of inhibition of metastasis of colorectal cancer by AMPK has not been reported yet.
Therefore, the present inventors confirmed the inhibitory effect of rosmarinic acid on metastatic colorectal cancer cells and found the present invention.
On the other hand, in reference to prior art related to rosmarinic acid, Korean Patent Laid-Open Publication No. 10-2005-0078743 discloses that hydroxyl phenyl derivatives of rosmarinic acid induce apoptosis in cancer cells.
However, the above-mentioned prior art has been tested on leukemic cell lines as well as on hydroxyl phenyl derivatives of rosmarinic acid, which is not relevant to the present invention.
The object of the present invention is to provide a pharmaceutical composition for preventing, ameliorating or treating metastatic colorectal cancer without using side effects by using a natural material-derived substance.
Particularly a pharmaceutical composition having an effect capable of substantially inhibiting the metastasis of colon cancer.
The object of the present invention is to provide a health functional food composition for preventing or ameliorating metastatic colorectal cancer, which can be used without side effects by using a natural product-derived substance.
The present invention provides a pharmaceutical composition containing ROSMARINIC ACID as an active ingredient to prevent, ameliorate, or treat colitis, thereby solving the technical problem.
The composition solves the technical problem by preventing, ameliorating, or treating colon cancer through the effect of regulating apoptosis-inducing effect and cell cycle in CT26 cell which is a mouse-derived metastatic colorectal cancer cell line.
The composition solves the technical problems by preventing, ameliorating, or treating colon cancer through its ability to inhibit the metastatic ability of colon cancer by modulating epithelial-mesenchymal conversion factor, migratory / invasive factor and AMPKa activator.
The composition according to the present invention has the effect of preventing, ameliorating, or treating colon cancer through CT26 cell, which is a mouse-derived metastatic colorectal cancer cell line, through the effect of inducing apoptosis and regulating cell cycle.
The composition according to the present invention has an effect of improving or treating the metastasis of colon cancer through its ability to inhibit the metastatic ability of colon cancer by controlling the epithelial-mesenchymal factor, migratory / invasive factor and AMPKa activator.
Fig. 1 is a graph showing the effect of rosemarinic acid on the survival rate of a mouse-derived metastatic colorectal cancer cell line CT26.
FIG. 2 is a graph showing the results of Annexin V assay to determine whether treatment with rosmarinic acid causes apoptosis in mouse derived metastatic colorectal cancer cell line CT26 cells.
FIG. 3 is a diagram showing Western blot analysis of the pathway of rosemarin-induced apoptosis in mouse derived metastatic colorectal cancer cell line CT26 cells.
FIG. 4 is a graph showing the effect of treatment with rosmarinic acid on the cell cycle in mouse-derived metastatic colorectal cancer cell line CT26 cells.
FIG. 5 is a graph showing the effect of treatment with rosmarinic acid on the expression of epithelial-mesenchymal transition (EMT) -related factors in mouse derived metastatic colorectal cancer cell line CT26 cells by Real-Time RT-PCR.
FIG. 6 is a microscopic photograph and a graph showing the effect of treatment with rosmarinic acid on the mobility in a mouse-derived metastatic colorectal cancer cell line CT26 cell.
FIG. 7 is a graph showing the expression of mobility-related factors by real-time RT-PCR in the mouse-derived metastatic colorectal cancer cell line CT26 cells treated with rosmarinic acid.
FIG. 8 shows Western blot analysis of the degree of phosphorylation of AMPKα in CT26 cells, a mouse-derived metastatic colorectal cancer cell line, treated with rosmarinic acid.
FIG. 9 shows the expression levels of MMP2 and MMP9 by using Compound C, an inhibitor of AMPKa, in real-time RT-PCR to determine whether the inhibitory effect of rosmaric acid was inhibited by AMPKa in CT26 cells, a metastatic colorectal cancer cell line derived from mice As shown in FIG.
The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.
Therefore, the embodiments, reference examples, experimental examples, production examples, and drawings described in the present specification are merely the most preferred examples of the present invention and do not represent all the technical ideas of the present invention. Therefore, It should be understood that various equivalents and modifications may be substituted for those embodiments.
Example 1. Rosemarinic acid of Preparation of pharmaceutical composition containing active ingredient
The pharmaceutical composition according to the present invention is for prevention, improvement or treatment of metastatic colorectal cancer and contains rosmarinic acid as an active ingredient.
Rosemaric acid is separated and purified from natural products such as vegetables and herbal medicines, and an effective concentration is prepared based on the experimental examples of the present invention. A pharmaceutical additive is added to the pharmaceutical composition such that the effective concentration of rosmarinic acid is maintained.
The composition of the present invention can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxy, hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used.
Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as calcium carbonate, sucrose, ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate talc are also used.
Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsion-freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
As the base of the suppository, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
In addition, the composition of the present invention can be administered to mammals such as rats, mice, livestock, and humans in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
Example 2. Rosemarinic acid of Preparation of Health Functional Food Composition Containing Active Ingredient
The health functional food composition according to the present invention is for prevention or improvement of metastatic colorectal cancer, and contains rosmarinic acid as an effective ingredient.
Rosemaric acid is separated and purified from natural products such as vegetables and herbal medicines, and an effective concentration is prepared based on the experimental examples of the present invention. Food functional additives are added to the health functional food composition such that the effective concentration of rosmarinic acid is properly maintained.
Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxy, hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
The composition of the present invention can be variously used for foods and beverages for prevention or improvement of colitis. Examples of foods to which the composition of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like, and they can be used in the form of powders, granules, tablets, have.
At this time, the amount of the composition in food or beverage is generally from 1 to 5% by weight of the total food weight of the health food composition of the present invention, and the health beverage composition contains 0.02 to 10 g, preferably 0.3 To 1 g.
The health beverage composition of the present invention contains, as an essential ingredient, the extract of Angelica keiskei L. as an essential ingredient in the indicated ratio, and there is no particular limitation to the liquid ingredient, and it may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages.
Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
In addition to the above, the composition of the present invention can be applied to various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and aging agents (cheese, chocolate etc.), pectic acid and its salts, , Protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
Experimental Example
One.
Cell viability measurement
(1) Experimental process
Cell viability was measured using the MTS assay. CT26, a mouse-derived metastatic colorectal cancer cell, is cultured on a 96-well plate, and then rosemaric acid is treated at different concentrations.
The cells were cultured for 24-96 hours in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum (FBS) at 5
(2) Experimental results
Fig. 1 is a graph showing the effect of rosemarinic acid on the survival rate of a mouse-derived metastatic colorectal cancer cell line CT26.
Referring to FIG. 1, the survival rate rapidly decreased to 70% at 72 and 96 hours in
Experimental Example
2. Cells in metastatic colorectal cancer cell line CT26
Self-destruction
Judo
(1) Experimental process
Annexin V assay was performed to determine whether the decrease in survival rate of CT26, a metastatic colorectal cancer cell by treatment with rosemarin, was induced by apoptosis.
CT26 cells were streaked in 6 well plates at 5 × 10 5 cells / well and treated with rosemaric acid for 48 hours.
The cells are removed by trypsin treatment and counted, and 1x10 6 cells are added to 1 ml of 1X binding buffer for FACS. Dissect 1 × 10 5 cells in a 1.5 ml tube and incubate for 15 minutes with Annexin V-FITC and PI reagent. Mix well with vortex and measure the degree of fluorescence staining with BD FACS calibur instrument.
(2) Experimental results
FIG. 2 is a graph showing the results of Annexin V assay to determine whether treatment with rosmarinic acid causes apoptosis in mouse derived metastatic colorectal cancer cell line CT26 cells.
Referring to FIG. 2, it can be seen that apoptosis (EARLY & LATE) is about 3.90% at 20 μM of rosmarinic acid and about 15.50% at 200 μM.
In FIG. 1, after 48 hours, the cell survival rate was about 85 to 96%. The results shown in FIG. 2 are consistent with the results shown in FIG.
In other words, the main cause of cell viability reduction is not cytotoxicity but cell
In self-destruction
It is clear that this is the result.
Experimental Example
3. Cells in metastatic colorectal cell line CT26
Self-destruction
Induction path
(1) Experimental process
CT26, a metastatic colorectal cancer cell, was placed in a 6-well plate at 5 × 10 5 / well and then treated overnight (0, 24, 48 h) with rosemaric acid at concentrations of 0, 20 and 200 μM.
The culture medium and drug were washed with PBS and lysed with lysis buffer (Santa Cruz, CA, USA). Cells were lysed and recovered using a scraper. After 5 × sample buffer (62.5 nM Tris-HCl, pH 6.8, 2% sodium dodecyl sulfate (SDS), 20% glycerol and 10% 2-mercaptoethanol) was added and heated at 95 ° C for 5 minutes, Use SDS-polyacrylamide gel electrophoresis for size classification and transfer to nitrocellulose membrane. Membrane was blocked with 0.1% PBST solution in buffer containing 5% BSA for 1 hour 30 minutes at room temperature. The primary antibody was reacted for more than 3 hours and washed with 0.1% PBST solution once every 15 minutes for a total of 3 times I got it. The secondary antibody was reacted for 45 minutes, washed with 0.1% PBST solution for 2 hours, and the band was confirmed using ECL detection solution.
(2) Experimental results
FIG. 3 is a diagram showing Western blot analysis of the pathway of rosemarin-induced apoptosis in mouse derived metastatic colorectal cancer cell line CT26 cells.
Procaface is a typical enzyme inducing apoptosis. Bcl-2 and Bcl-xl are proteins that inhibit apoptosis. PARP enzyme is a protein that inhibits apoptosis. GAPDH is an enzyme that transfers phosphate groups.
Referring to Figure 3,
Self-destruction
Inducing
Pro-cascade
Promoting expression,
Self-destruction
And that it is promoting,
AMPKα
And phosphorylation.
Experimental Example
4. Identification of cell cycle changes in metastatic colon cancer cell line CT26
(1) Experimental process
To determine whether the survival rate of CT26, which is a metastatic colorectal cancer cell by rosemarin treatment, was due to cell cycle arrest caused by the change of the cell cycle ratio, we used Muse Cell Cycle Kit (Millipore, MA, USA) Respectively.
CT26 cells were streaked in 6 well plates at 5 × 10 5 cells / well and treated with rosemaric acid for 48 hours. Cells treated with rosmarinic acid are fixed with 70% cold ethanol at -20 ℃ for more than 3 hours. After fixation, the cells are washed with PBS and the cells are reacted with 200 μl of Cell Cycle Reagent in a dark room for 30 minutes. The cell cycle of the samples is then analyzed with the Muse Cell Analyzer.
(2) Experimental results
FIG. 4 is a graph showing the effect of treatment with rosmarinic acid on the cell cycle in mouse-derived metastatic colorectal cancer cell line CT26 cells.
Referring to FIG. 4, it can be seen that the distribution of the cell cycle was changed according to the treatment with rosmarinic acid. That is,
200 [mu] M
At the time of treatment, the distribution of G0 / G1: S: G2 / M groups was higher than that of
Therefore, the cell cycle was regulated by treatment with rosemarinic acid, indicating that the survival rate of CT26, a metastatic colorectal cancer cell, was reduced.
Experimental Example
5. Epithelial-positive cells in metastatic colorectal cancer cell line CT26
Liver
Regulation of expression of conversion-related factors
(1) Experimental process
CT26, a metastatic colorectal cancer cell, was placed in a 6-well plate ( 5 × 10 5 cells / well) overnight, and treated with rosemaric acid for 48 hours. To determine the mRNA expression of epithelial-mesenchymal transition factors (E, N-cadherin, Slug, Twist, Vimentin), real-time RT-PCR method was used.
(2) Experimental results
FIG. 5 is a graph showing the effect of treatment with rosmarinic acid on the expression of epithelial-mesenchymal transition (EMT) -related factors in mouse derived metastatic colorectal cancer cell line CT26 cells by Real-Time RT-PCR.
The epithelial-mesenchymal transition (EMT) is essential in the process of transferring cancer cells to other organs. In these EMTs, the marker for epithelial cells is E-cadherin, and the markers for mesenchymal cells are N-cadherin and Vimentin. In addition, Slug and Twist are related factors that are increased during epithelial-mesenchymal transition.
Referring to FIG. 5, it can be confirmed that the expression of E-curerin is increased and the expression of N-cadherin, slug, twist, and visentin is decreased in a concentration-dependent manner of rosmarinic acid.
Therefore,
Liver
transform(
EMT
) ≪ / RTI > related factors, thereby inhibiting the metastasis of colorectal cancer.
Experimental Example
6. Reduced migration capacity of metastatic colorectal cancer cell line CT26
(1) Experimental process
A wound healing assay was performed to investigate the effect of rosemaric acid on migration, one of the transfection abilities. CT26, a metastatic colorectal cancer cell, is placed in a 6-well plate at 1 × 10 6 / well and stabilized overnight. After 80-90% of the cells are reached, a 200 μl pipet tip is used to scrape the center from top to bottom. Wash once with PBS, replace with fresh medium, and treat rosemaric acid for 48 hours. After culturing in a cell incubator, the migration patterns of the cells are observed under a microscope and then photographed (FIG. 6)
(2) Experimental results
FIG. 6 is a microscopic photograph and a graph showing the effect of treatment with rosmarinic acid on the mobility in a mouse-derived metastatic colorectal cancer cell line CT26 cell.
Referring to FIG. 6, when the density of cells is decreased depending on the concentration of rosmarinic acid
that
, The ability of the metastatic colon cancer cell line CT26 to migrate
Reduced
.
Experimental Example
7. Migration ability of metastatic colorectal cancer cell line CT26
Of related factors
Regulation of expression
(1) Experimental process
RT-PCR was used to determine mRNA expression levels of MMP-2, MMP-9, and matrix metalloproteinases. CT26, a metastatic colorectal cancer cell, was stabilized overnight at 5 × 10 5 cells / well. Rosemaric acid was treated with rosemarin for 48 hours. Cells were recovered, RNA extracted and cDNA synthesized, and mRNA levels were confirmed by PCR.
(2) Experimental results
FIG. 7 is a graph showing the expression of mobility-related factors by real-time RT-PCR in the mouse-derived metastatic colorectal cancer cell line CT26 cells treated with rosmarinic acid.
Referring to FIG. 7, it can be confirmed that the infiltration ability of the metastatic colorectal cancer cell line CT26 is decreased in a concentration-dependent manner of rosemaric acid .
Experimental Example
8. Metastatic colorectal cancer cell line CT26
AMPKα
Check phosphorylation degree
(1) Experimental process
CT26, a metastatic colorectal cancer cell, was placed in a 6-well plate ( 5 × 10 5 cells / well) overnight, and treated with 200 μM of rosemaric acid per concentration (0, 12, 24 and 48 h). The culture medium and drug were washed with PBS and lysed with lysis buffer (Santa Cruz, CA, USA). Cells were lysed and recovered using a scraper. After 5 × sample buffer (62.5 nM Tris-HCl, pH 6.8, 2% sodium dodecyl sulfate (SDS), 20% glycerol and 10% 2-mercaptoethanol) was added and heated at 95 ° C for 5 minutes, SDS-polyacrylamide gel is used to sort by electrophoresis and transferred to a nitrocellulose membrane. Membrane was blocked with 0.1% PBST solution in buffer containing 5% BSA for 1 hour 30 minutes at room temperature. The primary antibody was reacted for more than 3 hours and washed with 0.1% PBST solution once every 15 minutes for a total of 3 times I got it. The secondary antibody was reacted for 45 minutes, washed with 0.1% PBST solution for 2 hours, and the band was confirmed using ECL detection solution.
(2) Experimental results
FIG. 8 shows Western blot analysis of the degree of phosphorylation of AMPKα in CT26 cells, a mouse-derived metastatic colorectal cancer cell line, treated with rosmarinic acid.
AMP-activated protein kinase (AMPK) plays an important role in the regulation of energy recognition and homeostasis in vivo, especially in the metabolism of sugars and fats. The abnormality of these energy sensors is related to the development of cancer including metabolic diseases.
Referring to FIG. 8,
pAMPK
,
AMPK
And
GAPDH's
The band appeared to be dark even after 48 hours, and the treatment with rosemarin was performed in CT26 cells, a metastatic colorectal cancer cell line
AMPKα
Phosphorylation is regulated to decrease cancer cell metastasis ability.
Experimental Example
9. Metastatic colorectal cancer cell line CT26
AMPKα and
Cancer cells
Transferability
Confirm the relationship between
(1) Experimental process
CT6, a metastatic colorectal cancer cell line, was placed in a 6-well plate ( 5 × 10 5 / well) for overnight. Compound C, an inhibitor of AMPKα, was treated with 10 μM for 4 h and treated with 200 μM rosemaric acid for 48 h. The mRNA expression level of MMP-2 and MMP-9 was confirmed by real-time RT-PCR (Figure 9).
(2) Experimental results
FIG. 9 shows the expression levels of MMP2 and MMP9 by using Compound C, an inhibitor of AMPKa, in real-time RT-PCR to determine whether the inhibitory effect of rosmaric acid is inhibited by AMPKa in CT26 cells, a metastatic colorectal cancer cell line derived from mouse As shown in FIG.
Referring to FIG. 9,
Compound
C group
MMP
-2 and MMP-9
High expression level
As shown, the inhibitory effect of rosmarinic acid
AMPKα
As shown in Fig.
Claims (5)
Wherein said composition is for preventing, ameliorating or treating colorectal cancer through CT26 cell, which is a metastatic colorectal cancer cell line derived from a mouse, through an effect of regulating apoptosis-inducing effect and cell cycle.
Wherein said composition is for preventing, ameliorating or treating colorectal cancer through the efficacy of inhibiting the metastatic ability of colon cancer by modulating epithelial-mesenchymal conversion factor, migration / invasiveness factor and AMPKa activator.
Wherein said composition exhibits said efficacy at 20-200 [mu] M of rosmarinic acid.
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|---|---|---|---|---|
| KR20200009933A (en) * | 2018-07-20 | 2020-01-30 | 성균관대학교산학협력단 | pharmaceutical composition for preventing or treating cervical cancer or head and neck cancer containing a novel S6K1 inhibitor as an active ingredient |
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2016
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Cited By (1)
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|---|---|---|---|---|
| KR20200009933A (en) * | 2018-07-20 | 2020-01-30 | 성균관대학교산학협력단 | pharmaceutical composition for preventing or treating cervical cancer or head and neck cancer containing a novel S6K1 inhibitor as an active ingredient |
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