Tumor cell proliferation inhibitor

Abstract

To provide a tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, containing mannose having a higher tumor cell proliferation inhibitory effect so as not to require the intake of a large amount of mannose.SOLUTION: The present invention is a tumor cell proliferation inhibitor containing mannose having a high α - type ratio, and is effective for prevention and / or treatment of cancer. Since the tumor cell proliferation inhibitor of the present invention has a higher tumor cell proliferation inhibitory action than conventionally known mannose and is derived from a natural raw material, it can be safely ingested or administered.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a tumor cell proliferation inhibitor, specifically to a tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, which contains as an active ingredient D-mannose having a higher α-type than β-type. [Background technology]

[0002] According to a survey by the Ministry of Health, Labor and Welfare, malignant neoplasms (tumors) are the leading cause of death among Japanese people, far ahead of heart disease, which is the second leading cause. Reflecting this, many recent research findings have advanced our understanding of the mechanisms of tumor development. These findings have revealed that various chemicals can control tumor development and growth, and they are being used for medicinal purposes as antitumor agents. However, while the various chemicals currently in use have strong antitumor effects, they are also cytotoxic to normal cells as well as tumor cells, resulting in serious side effects. Therefore, there is a strong demand for safe tumor cell growth inhibitors that have very little cytotoxicity and can inhibit the growth of tumor cells only.

[0003] It is well known that tumor cells have an increased cellular metabolism. In particular, tumor cells have the property of consuming large amounts of sugar compared to normal cells. Because many tumor cells exhibit enhanced glucose uptake, this property is utilized in cancer screening, known as PET scanning. PET scanning uses fluorodeoxyglucose (FDG), which has a structure similar to glucose, to detect intracellular accumulation of FDG and identify the presence and location of tumor cells. Because of this increased glucose uptake in tumor cells, research is also being conducted into their response to monosaccharides other than glucose. For example, mannose is taken up by tumor cells via the same transporter as glucose, but it accumulates intracellularly as mannose-6-phosphate, inhibiting further glucose metabolism in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, and glycan synthesis. Consequently, mannose has been reported to suppress the growth of various types of tumor cells and promote cell death in response to major chemotherapeutics (see, for example, Non-Patent Document 1).

[0004] Mannose exists in both D and L forms, but since the L form does not exist in nature, D-mannose is referred to herein as mannose. Furthermore, mannose exists as stereoisomers (anomers) of α- and β-mannose. When the hydroxyl group on the C1 carbon and the hydroxymethyl group on the C5 carbon are in opposite directions, it is called the α-form, and when they are in the same direction, it is called the β-form. Generally, in aqueous solution, the anomers interconvert to form mannopyranose, and the α- and β-forms exist in equilibrium.

[0005] Currently, the mannose used in many foods and other foods is mainly produced by isomerizing glucose using a molybdic acid catalyst (see, for example, Patent Document 1), but it has been reported that when this isomerized mannose is dissolved in an aqueous solution, the α- and β-forms reach equilibrium over time, with approximately 67% α and 33% β. When mannose is crystallized from methanol, the α-form is obtained, and when crystallized using glacial acetic acid, the β-form is obtained. However, even crystallized mannose, when dissolved in an aqueous solution, reaches equilibrium over time with the above-mentioned ratio of α to β (see, for example, Non-Patent Documents 2 and 3). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Special Publication No. 63-12072 [Non-patent literature]

[0007] [Non-Patent Document 1] Pablo Sierra Gonzalez, et. al., “Mannose impairs tumor growth and enhances chemotherapy” NATURE, vol 563, 719-723 (2018) [Non-patent document 2] The Merck Index, published January 1, 2006, 14th edition, p5747 [Non-patent document 3] Chemistry Encyclopedia, Morikita Publishing, November 2012, 2nd Edition, "Mannose" Summary of the Invention [Problem to be solved by the invention]

[0008] Orally administered mannose is absorbed from the small intestine and delivered throughout the body via the bloodstream, where it exhibits antiproliferative effects on various tumor cells, but does not accumulate specifically in tumor cells. Therefore, in order to increase the mannose concentration throughout the body, it is necessary to ingest large amounts of mannose. However, when large amounts of mannose are ingested, diarrhea and vaginal flushing have been reported as side effects in some cases.

[0009] An object of the present invention is to provide a tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, which contains mannose and has a higher tumor cell proliferation inhibitory effect, thereby eliminating the need to ingest large amounts of mannose. [Means for solving the problem]

[0010] In order to solve the above problems, the present inventors have conducted extensive research and have found that mannose with a high ratio of α-mannose has a strong inhibitory effect on tumor cell proliferation, leading to the completion of the present invention.

[0011] That is, the present invention is summarized as follows (1) to (7). (1) A tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, comprising as an active ingredient mannose in which the ratio of α-mannose to total mannose is 70% or more. (2) A tumor cell proliferation inhibitor according to (1), wherein the mannose having a ratio of alpha-mannose to total mannose of 70% or more is derived from at least one species selected from the group consisting of mannan, glucomannan, galactomannan and natural products containing them. (3) The tumor cell proliferation inhibitor according to (2), wherein the glucomannan is derived from konjac root. (4) The tumor cell proliferation inhibitor according to (1), wherein the cancer is a cancer of the digestive system. (5) The tumor cell proliferation inhibitor according to (1), wherein the cancer is colon cancer. (6) A pharmaceutical or quasi-drug containing the tumor cell proliferation inhibitor described in (1). (7) A food or drink composition comprising the tumor cell proliferation inhibitor described in (1). [Effects of the Invention]

[0012] The tumor cell proliferation inhibitor of the present invention contains a large amount of α-mannose, and therefore has an excellent tumor cell proliferation inhibitory effect, making it suitable for use in the prevention and / or treatment of cancer. Because of its high tumor cell proliferation inhibitory effect, it can be expected to be effective even with a small dose. Furthermore, the use of mannose derived from natural products allows for safe ingestion or administration. [Brief explanation of the drawings]

[0013] [Figure 1] Glucomannan-derived mannose inhibits cell proliferation in colon cancer spheroids (cell line: HC6T) [Figure 2] Glucomannan-derived mannose inhibits cell proliferation in colon cancer spheroids (cell line: HC106T) [Figure 3] Glucomannan-derived mannose inhibits cell proliferation in colon cancer spheroids (cell line: HC108T) DETAILED DESCRIPTION OF THE INVENTION

[0014] The present invention will be described in detail below. The tumor cell proliferation inhibitor of the present invention contains, as an active ingredient, mannose in which the ratio of α-mannose to total mannose is 70% or more, preferably 75% or more, and more preferably 80% or more. If the ratio is less than 70%, the tumor cell proliferation inhibitor does not exhibit a high inhibitory effect. Furthermore, "containing as an active ingredient" means containing an amount of mannose effective for prevention or treatment, and includes being acceptable for animal use and human pharmaceutical use. Since mannose exists in α-type and β-type, the "ratio of α-type mannose to total mannose" here refers to the weight ratio of α-type / (α-type + β-type) calculated from the GC area when measured under the following conditions.

[0015] (Method for measuring the ratio of α-mannose to total mannose) To 0.5 g of mannose, 12 mL of pyridine, 8 mL of 1,1,1,3,3,3-hexamethyldisilazane, and 4 mL of chlorotrimethylsilane were added and dissolved by shaking. The mixture was then left to stand at room temperature for 4 hours. The mixture was then filtered through a 0.45 μm filter, and the filtrate was analyzed by gas chromatography under the following conditions. (Gas chromatography measurement conditions) Analytical column: 5% diphenyl-95% dimethylpolysiloxane chemically bonded low-polarity column (length 30 m x inner diameter 0.32 mm x film thickness 0.4 μm) Heating conditions: Heat from 110°C to 250°C at 5°C / min, then hold at 250°C for 5 minutes Sample introduction temperature: 250℃ Carrier gas: Helium Column gas flow rate: 2.0 mL / min Detector and detection temperature: Hydrogen flame ionization detector, 250°C Injection port: (Temperature) 250°C, (Injection volume) Split 1 μL (Split ratio: 30:1)

[0016] The mannose used in the present invention may be of any origin, but from the standpoint of safety, mannose produced from natural products is preferred. The source of such mannose is preferably at least one selected from the group consisting of mannan, glucomannan, galactomannan, and natural products containing them. Specific raw materials are not particularly limited as long as they contain mannan, glucomannan, or galactomannan as a constituent sugar. Examples include coconut, palm, and their oil extraction residues (copra meal, palm kernel meal, etc.), ivory palm (seed), konjac root and its processed products (coarse flour, refined flour, flying flour, etc.), guar beans and their processed products (guar gum, etc.), coffee beans or their extraction residues (coffee grounds, etc.), and locust beans and their processed products (carob powder, locust bean gum, etc.). Among these, konjac root and its processed products are preferred from the standpoint of high content of the constituent sugars and low cost. The natural product may be used as a raw material either directly or in a purified form. A mixture of these may also be used.

[0017] In the present invention, in order to produce mannose having a high proportion of the α-type, a preferred method is to obtain mannose by hydrolyzing at least one selected from the group consisting of mannan, glucomannan, galactomannan, and natural products containing them. When hydrolyzing at least one selected from the group consisting of mannan, glucomannan, galactomannan, and natural products containing them, the hydrolysis can be carried out using an acid, an alkali, an enzyme, or the like, or under a high-temperature, high-pressure environment. Among these, hydrolysis using an enzyme is preferred because it produces fewer by-products, has fewer limitations on the equipment required for the hydrolysis step, and places less strain on the environment.

[0018] The enzyme used in the above-mentioned enzymatic treatment of the present invention is not particularly limited as long as it has the activity of acting on at least one selected from the group consisting of mannan, glucomannan, galactomannan, and natural products containing them to release monosaccharides, but enzymes that act on the main chain of hemicellulose to release monosaccharides, such as mannanase, galactomannanase, glucomannanase, mannosidase, α-xylidase, xyloglucanase, arabinanase, β-xylosidase, xylanase, α-arabinofuranosidase, cellulase, etc., are preferred. Among these, mannan-degrading enzymes such as mannanase, mannosidase, or galactomannanase are preferred.

[0019] If necessary, enzymes such as glucosidase and galactosidase, which liberate glucose and galactose present in the branched side chains of hemicellulose, can be used in combination with enzymes acting on the main chain. Furthermore, the mannose yield can be increased by mixing two or more enzymes with different activities. The enzymes used may be any fractions that have mannose-liberating activity from the culture of the bacterial strain from which the enzyme originates. Furthermore, fractions containing these enzymes can be purified or partially purified by conventional methods before use, if necessary.

[0020] The mannose liberation reaction conditions for the enzymes reacting with at least one selected from the group consisting of mannan, glucomannan, galactomannan, and natural products containing them can be optimized for each enzyme. The reaction temperature is preferably set so as not to inactivate the enzyme, for example, at 30 to 70°C, preferably 40 to 60°C, and more preferably 50 to 60°C. The reaction time depends on factors such as the amount of enzyme used, but is typically set between 3 and 72 hours for operational reasons. The reaction pH also depends on the type of enzyme used, but is preferably between 2 and 9, more preferably between 2.5 and 8, and even more preferably between 3 and 6.

[0021] The released mannose may be purified to further increase the purity of the mannose. Purification can be performed by known methods, such as decolorization using bone charcoal, activated carbon, carbon dioxide, adsorption resin, magnesia method, etc., and desalting and deacidification using ion exchange resin, ion exchange membrane, electrodialysis, etc. The combination of purification methods and purification conditions may be appropriately selected depending on the amounts of pigments, salts, acids, etc. in the mannose-containing reaction solution and other factors.

[0022] The form of the mannose of the present invention is not particularly limited, and examples thereof include an aqueous solution containing mannose, a powder, etc. To obtain a powder, known techniques such as solid-liquid separation, resin purification, membrane purification, concentration, spray drying, freeze drying, and crystallization can be used.

[0023] The tumor cell proliferation inhibitor of the present invention is used for the prevention and / or treatment of cancer. "Use for the prevention and / or treatment of cancer" means use in a patient suffering from cancer for at least one of the following purposes: suppression of cancer progression, suppression of cancer or tumor growth, prevention of cancer onset, and prevention of cancer recurrence.

[0024] The types of cancers that are the subject of the present invention are not particularly limited, but include cancers of the digestive system (e.g., colorectal cancer (including colon cancer, colon adenocarcinoma, and rectal cancer), oral cancer, pharyngeal cancer, esophageal cancer, stomach cancer, liver cancer, gallbladder cancer, biliary tract cancer, spleen cancer, small intestine cancer, duodenal cancer, pancreatic cancer, and liver cancer), cancers of the nervous system (e.g., brain tumors and cervical cancer), cancers of the musculoskeletal system (e.g., sarcoma, osteosarcoma, and myeloma), cancers of the urinary system (e.g., bladder cancer and kidney cancer), and cancers of the reproductive system (e.g., breast cancer, uterine cancer, ovarian cancer, testicular cancer, and prostate cancer). , respiratory system cancers (e.g., lung cancer), hematopoietic system cancers (e.g., leukemias such as acute or chronic myeloid leukemia, acute promyelocytic leukemia, acute or chronic lymphocytic leukemia, malignant lymphoma (lymphosarcoma), angiosarcoma, multiple myeloma, myelodysplastic syndrome, primary myelofibrosis, hemangiopericytoma), thyroid cancer, parathyroid cancer, tongue cancer, malignant melanoma, mast cell tumor, cutaneous histiocytoma, lipoma, hair follicle tumor, skin papilloma, sebaceous adenoma, basal cell carcinoma, etc. Among these, application to cancers of the digestive system is preferred, and application to colon cancer is more preferred.

[0025] The dosage of the tumor cell proliferation inhibitor of the present invention can be appropriately adjusted taking into consideration the purpose of use, the recipient, the recipient's gender, age, weight, and stage of cancer progression, etc. This dosage varies depending on various conditions, and a small dosage or frequent administration may be sufficient in some cases, while a large dosage or frequent administration may be required in other cases. The administration regimen may be a single administration or frequent administration, but frequent administration is preferred because the effect is sustained with continued administration. The concentration of mannose to be administered is preferably 2.5 mM to 200 mM, and more preferably 4 mM to 150 mM.

[0026] The dosage form of the tumor cell proliferation inhibitor of the present invention is not particularly limited, and examples thereof include oral administration preparations (tablets, coated tablets, powders, granules, capsules, liquids, etc.), airway administration preparations, intraperitoneal administration preparations, intravenous administration preparations, injections, suppositories, patches, ointments, etc., with oral administration preparations, airway administration preparations, and intravenous administration preparations being preferred. Intravenous administration preparations include intravenous injection preparations and intravenous drip injection preparations. In humans, oral administration preparations and intravenous administration preparations are preferred.

[0027] For formulation, the tumor cell proliferation inhibitor of the present invention may be mixed with non-toxic, inert, pharmaceutically acceptable excipients, such as solid, semi-solid, or liquid diluents, dispersants, fillers, and carriers, as necessary. Furthermore, within the range that does not impair the effects of the present invention, stabilizers, preservatives, pH adjusters, binders, disintegrants, surfactants, lubricants, flow enhancers, flavoring agents, colorants, flavoring preservatives, vehicles, physiological saline, and other medicinal agents may be contained as additives.

[0028] The tumor cell growth inhibitor of the present invention may be administered in combination with other cancer therapeutic agents or therapies. Treatment methods that can be used in combination with the tumor cell growth inhibitor of the present invention include chemotherapy, radiation therapy, chemoradiotherapy, immunotherapy, hormone therapy, surgery, or stem cell therapy. Among these, chemotherapy is preferred, and preferred chemotherapeutic agents for use in chemotherapy include, but are not limited to, platinum chemotherapy agents, anthracycline therapeutic agents, and alkylating chemotherapy agents. Among these, cisplatin is preferred as a platinum chemotherapy agent, and doxorubicin is preferred as an anthracycline therapeutic agent. Concomitant administration refers to administration simultaneously with the administration of the tumor cell growth inhibitor of the present invention, or before or after administration of the tumor cell growth inhibitor of the present invention. Alternatively, the tumor cell growth inhibitor of the present invention and the other cancer therapeutic agent can be mixed to form a single formulation. [Example]

[0029] The present invention will be specifically explained by the following examples, but the present invention is not limited to these examples.

[0030] <Analysis of α- and β-mannose> 0.5 g of sample was weighed and placed in a 25 mL volumetric flask. 12 mL of pyridine, 8 mL of 1,1,1,3,3,3-hexamethyldisilazane, and 4 mL of chlorotrimethylsilane were added, and the mixture was shaken to dissolve. The mixture was then allowed to stand for 4 hours. The insoluble matter was removed from this solution by filtration using a 0.45 μm filter, and the analytical sample was prepared. GC analysis was performed under the following conditions. The weight ratio of α-mannose to β-mannose was determined from the GC area, and the ratio of α-mannose to total mannose was calculated. Equipment: Agilent Technologies 7890B GC System Column: INERT CAP-5 (30 m x 0.32 mm ID, film thickness 0.4 μm) Heating conditions: Heat from 110°C to 250°C at 5°C / min, then hold at 250°C for 5 minutes Sample introduction temperature: 250℃ Carrier gas: Helium Column gas flow rate: 2.0 mL / min Detector and detection temperature: Hydrogen flame ionization detector, 250°C Injection port: (Temperature) 250°C, (Injection volume) Split 1 μL (Split ratio: 30:1)

[0031] <Production of glucomannan-derived mannose> The enzyme reaction was initiated by adding 10 mL of ion-exchanged water containing 25 mg of mannanase (Amano Enzyme Co., Ltd., Mannanase BGM "Amano") to 1 g of glucomannan (fine flour) purified from konjac root. After 48 hours of enzyme treatment at 58°C, the enzyme was inactivated at 96°C for 10 minutes. After filtering using filter paper (No. 5C) to remove water-insoluble materials, the mixture was concentrated using a rotary evaporator to produce a sugar solution with a mannose concentration of 40 g / 100 g. [Example]

[0032] The sugar solution containing the glucomannan-derived mannose obtained above (24 hours or more after production) was subjected to GC analysis to determine the weight ratio of α- to β-type mannose. As a result, the ratio of α- to β-type mannose calculated from the GC area was 80% and 20%, respectively, indicating that mannose with a high α-type content was obtained. Next, using the HC6T colon cancer spheroid strain, the reactivity of the glucomannan-derived mannose obtained above to colon cancer spheroids was evaluated by image analysis. All experiments were performed three independent times. Colon cancer spheroids were derived from colon cancer patients. In the present invention, the HC6T strain (Kyoto University strain; the same applies to other strains below) was used. The above spheroids, which had been frozen and stored, were thawed and cultured to an appropriate cell mass. The culture medium used was Advanced DMEM / F12 (Thermo Fisher), 5% FBS, 10 μM Y27632, 1 μM SB431542, 50 ng / ml EGF, 100 ng / ml FGF-basic, 100 units / ml penicillin, 0.1 mg / ml streptomycin, 2 mM L-glutamine, and 5 μg / ml Plasmocin (Invivogen, San Diego, CA). Cells for drug susceptibility testing were seeded into 96-well plates (TPP_96F) at 800 cells / well, in four wells. The glucomannan-derived mannose obtained above was added to the culture medium to adjust the mannose concentration to 125 mM. The day after seeding was designated Day 0, and images were taken on Day 3 using a Cell3 imager duos (SCREEN Holdings, model CC-8000, software version 1.6 Rev.2.0.1). Using manual focus mode, the central 61% of the well was set as the imaging range (a size that would fit the entire gel within the range), and consecutive cross-sectional images were taken at 15 points every 50 μm along the z-axis, and output as fully focused images. The reaction was initiated by changing the medium on Day 0. The culture was continued without changing the medium until the end of the experiment. The imaging intervals were kept constant. The Measure function of the analysis software [SCREEN Holdings, Software ver. 1.6 Rev. 2.0.1] was used to calculate the area values ​​by applying the program to the spheroid image data. Furthermore, volume data was calculated from the calculated area values ​​using the program software R. To calculate the volume data, a program was used to calculate the radius from the area, the volume of the sphere from the radius value, and the total volume per well. The volume ratio was calculated from the volume values ​​of Day 3 / Day 0, and the ratio of each concentration was calculated and compared, assuming the control was 1. The volume ratio (Day 3 / Day 0) of each data point was calculated from the obtained volume data. A t-test was used to test for significance with the control group. A p value of less than 0.05 was considered significant. The results are shown in Figure 1. Note that the vertical axis, GEI, stands for growth effect index. Comparative Example 1

[0033] A mannose solution (Tokyo Chemical Industry Co., Ltd.) sold as a reagent was prepared with a mannose concentration of 40 g / 100 g, and after leaving it to stand at room temperature for 24 hours, the weight ratio of α-type to β-type was analyzed by GC. As a result, the ratio of α-type to β-type calculated from the GC area was 67% and 33% (specific rotation [α] D 20 +14.0), which is the ratio of a typical mannose solution. Next, a test was conducted using the same colon cancer spheroids as in Example 1, except that the glucomannan-derived mannose in Example 1 was replaced with commercially available mannose. The results are shown in Figure 1.

[0034] A significant difference test between Example 1 and Comparative Example 1 revealed a p-value of p=0.007, indicating that the mannose of Example 1 had a significantly stronger tumor cell proliferation inhibitory effect. As is clear from Figure 1, mannose with an α-mannose ratio of 70% or more exhibits a stronger cell proliferation inhibitory effect on colon cancer cells compared to mannose with an α-mannose ratio of less than 70%. [Example]

[0035] The same test was carried out using colon cancer spheroids as in Example 1, which was a test using glucomannan-derived mannose in which the ratio of α-mannose to total mannose was 80%, except that the colon cancer spheroid cells were changed from the HC6T strain to the HC106T strain. The results are shown in Figure 2.

[0036] The same test was carried out using colon cancer spheroids, except that the glucomannan-derived mannose used in Example 2 was replaced with commercially available mannose, which has a 67% α-mannose ratio relative to total mannose. The results are shown in Figure 2.

[0037] A significance test was performed between Example 2 and Comparative Example 2, with a p-value of p=0.0000007, indicating that the mannose of Example 2 had a significantly stronger tumor cell proliferation inhibitory effect. As is clear from Figure 2, mannose with an α-mannose ratio of 70% or more exhibits a stronger cell proliferation inhibitory effect on colon cancer cells compared to mannose with an α-mannose ratio of less than 70%. [Example]

[0038] A test was conducted using the same colon cancer spheroids as in Example 1, which was a test using glucomannan-derived mannose in which the ratio of α-mannose to total mannose was 80%, except that the colon cancer spheroid cells were changed from the HC6T strain to the HC108T strain. The results are shown in Figure 3. Comparative Example 3

[0039] The same test was carried out using colon cancer spheroids, except that the glucomannan-derived mannose used in Example 3 was replaced with commercially available mannose, which has a 67% α-mannose ratio relative to total mannose. The results are shown in Figure 3.

[0040] A significance test was performed between Example 3 and Comparative Example 3, with a p-value of p=0.00006, indicating that the mannose of Example 3 had a significantly stronger tumor cell proliferation inhibitory effect. As is clear from Figure 3, mannose with an α-mannose ratio of 70% or more exhibits a stronger cell proliferation inhibitory effect on colon cancer cells compared to mannose with an α-mannose ratio of less than 70%. As is clear from these examples, mannose with an α-mannose ratio of 70% or more exhibited a very strong cell proliferation inhibitory effect. Therefore, it is presumed that a tumor cell proliferation inhibitor containing mannose with an α-mannose ratio of 70% or more as an active ingredient will have a high tumor cell proliferation inhibitory effect, and can be expected to be effective even when administered in small amounts to the subject. In particular, the mannose with an α-mannose ratio of 70% or more used in the present invention is derived from a natural product and can therefore be safely ingested or administered.

Claims

1. A tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, comprising as an active ingredient mannose in which the ratio of α-mannose to total mannose is 70% or more.

2. The tumor cell proliferation inhibitor according to claim 1, wherein the mannose having a ratio of alpha-mannose to total mannose of 70% or more is derived from at least one species selected from the group consisting of mannan, glucomannan, galactomannan and natural products containing them.

3. The tumor cell proliferation inhibitor according to claim 2, wherein the glucomannan is derived from konjac root.

4. The tumor cell proliferation inhibitor according to claim 1, wherein the cancer is a cancer of the digestive system.

5. The tumor cell proliferation inhibitor according to claim 1, wherein the cancer is colon cancer.

6. A pharmaceutical or quasi-drug comprising the tumor cell proliferation inhibitor according to claim 1.

7. A food or drink composition comprising the tumor cell proliferation inhibitor according to claim 1.

Images