Tumor cell proliferation inhibitor

Abstract

An object of the present invention is to provide a tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, comprising mannose and cyclodextrin.SOLUTION: The tumor cell proliferation inhibitor comprises mannose and cyclodextrin and is effective for preventing and / or treating cancer. Since the tumor cell proliferation inhibitor of the present invention has a higher tumor cell proliferation inhibitory action than mannose alone, it can be ingested or administered in a small amount.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a tumor cell proliferation inhibitor, particularly to a tumor cell proliferation inhibitor containing mannose and cyclodextrin for use in the prevention and / or treatment of cancer. [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 antitumor agents that have minimal cytotoxicity and can inhibit tumor cell growth 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 can be ingested by consuming foods containing mannose or mannose itself, but β-mannose, one of the anomers of mannose, has a distinctive bitter taste, and to suppress this unpleasant taste, a composition containing mannose combined with dietary fiber (cyclodextrin) has been proposed as being able to suppress the bitterness (see Patent Document 1).Furthermore, a method has also been proposed for enhancing the anticancer activity of a water extract of Ashwagandha leaves by using cyclodextrin (see Patent Document 2). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2011-254749 [Patent Document 2] International Publication No. 2015 / 115512 [Non-patent literature]

[0006] [Non-Patent Document 1] Pablo Sierra Gonzalez, et. al., “Mannose impairs tumor growth and enhances chemotherapy” NATURE, vol 563, 719-723 (2018) Summary of the Invention [Problem to be solved by the invention]

[0007] Orally administered mannose is absorbed from the small intestine and delivered throughout the body via the bloodstream, where it acts on various cells. However, because it does not specifically accumulate in tumor cells, it is necessary to ingest large amounts of mannose to increase the mannose concentration throughout the body. Ingestion of large amounts of mannose has been reported to cause diarrhea and vaginal flushing as side effects in some cases.

[0008] Furthermore, while it is known that some additives affect the stability and efficacy of active ingredients, Patent Document 1 focuses on suppressing the bitterness of a composition of cyclodextrin and mannose, and does not describe or suggest the composition's tumor cell proliferation inhibitory effect. Patent Document 2 describes that a composition obtained by mixing an aqueous extract of Ashwagandha leaves with cyclodextrin has high anticancer activity, but because the mechanisms of action of the aqueous extract of Ashwagandha leaves and mannose on tumor cells are different, the technology in this patent document may not necessarily be applicable to mannose.

[0009] It is known that cyclodextrin can be useful in preparing pharmaceutical substances according to the dosage form of the pharmaceutical, but it is well recognized in the pharmaceutical industry that it is not effective for all substances. For example, the aforementioned Patent Document 2 describes that the combined use of a drug and cyclodextrin improves anticancer activity, but International Publication No. 2007 / 026869 and JP-A-2024-520888 describe that the combined effect of a drug and cyclodextrin is not high.

[0010] Therefore, an object of the present invention is to provide a tumor cell proliferation inhibitor containing mannose for use in the prevention and / or treatment of cancer, which exhibits a high tumor cell proliferation inhibitory effect even at low doses. [Means for solving the problem]

[0011] In order to solve the above problems, the present inventors have conducted extensive research and have found that a composition containing cyclodextrin and mannose has a strong inhibitory effect on tumor cell proliferation, thereby completing the present invention.

[0012] That is, the present invention is summarized as follows (1) to (6). (1) A tumor cell proliferation inhibitor for use in the prevention and / or treatment of cancer, comprising mannose and cyclodextrin. (2) The tumor cell proliferation inhibitor according to (1), wherein the mannose is derived from at least one 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]

[0013] The tumor cell proliferation inhibitor of the present invention contains mannose and cyclodextrin and can be used for the prevention and / or treatment of cancer. Because it has a higher tumor cell proliferation inhibitory effect than mannose alone, it can be expected to be effective even with a small dose. Furthermore, the use of naturally derived mannose allows for safe ingestion or administration. [Brief explanation of the drawings]

[0014] [Figure 1] Inhibitory effect of a composition of mannose derived from konjac yam and gamma-cyclodextrin on tumor cell proliferation [Figure 2] Inhibitory effect of a composition of mannose derived from konjac yam and gamma-cyclodextrin on tumor cell proliferation [Figure 3] Antitumor cell proliferation effect of palm kernel meal-derived mannose and α-cyclodextrin composition DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention will be described in detail below. The mannose used in the present invention may be of any origin, either D- or L-isomer. Examples of mannose include mannose obtained by hydrolyzing mannose-containing raw materials, such as mannan, glucomannan, and galactomannan, which are natural sugar constituents, with acid, alkali, enzymes, or supercritical (subcritical) water; mannose obtained by isomerizing fructose using mannose isomerase as an enzyme; mannose obtained by isomerizing glucose using glucose isomerase and mannose isomerase as enzymes; mannose obtained by thermal epimerization of glucose using a catalyst containing a metal such as molybdic acid; fractions thereof; mixtures thereof; and commercially available mannose. Among these, from the viewpoint of safety, mannose obtained by hydrolyzing at least one selected from mannan, glucomannan, galactomannan, and natural products containing them is preferred.

[0016] When producing mannose from natural products, the mannan, glucomannan, galactomannan, or natural products containing them as constituent sugars are not particularly limited as long as they contain mannan, glucomannan, or galactomannan as constituent sugars. 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 and their extraction residues (coffee grounds), locust beans and their processed products (carob powder, locust bean gum, etc.). Among these, copra meal, palm kernel meal, konjac root, and their processed products are preferred, with konjac root and its processed products being more preferred, from the viewpoints of high content of the constituent sugars and low cost. The natural products may be used as raw materials themselves, or purified products may be used. Furthermore, mixtures thereof may also be used.

[0017] In the present invention, the enzyme used to treat the above-mentioned natural products with an enzyme 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, and cellulase, are preferred. Among these, mannan-degrading enzymes such as mannanase, mannosidase, and galactomannanase are preferred.

[0018] The mannose liberation reaction conditions for the enzymes reacting with mannan, glucomannan, galactomannan, or natural products containing these sugars 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.

[0019] Mannose obtained by decomposition of natural products with acids, alkalis, enzymes, supercritical (subcritical) water, etc. 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, carbonation, adsorption resins, magnesia, etc., and desalting and deacidification using ion exchange resins, ion exchange membranes, 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. The form of the mannose of the present invention is not particularly limited, and examples 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. From the viewpoint of ease of handling, a powder is preferred. Mannose exists as stereoisomers (anomers), namely, α- and β-mannose, and generally in aqueous solution, the anomers are interconverted to form mannopyranose, resulting in an equilibrium between α- and β-mannose. The mannose of the present invention preferably has an α-type ratio of more than 50% to the total mannose. A known measurement method can be used to measure the α-type.

[0020] Cyclodextrins are oligosaccharides consisting of glucose units linked together in a ring via α-1,4 bonds, and are also known as cyclic oligosaccharides. They are called α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin depending on the number of glucose units. Their properties, such as the size of the cavity in the ring structure and their water solubility, vary depending on the type. These properties are utilized in a variety of applications, including improving drug bioavailability, stabilizing various pigments and functional food ingredients, suppressing unpleasant flavors, and solubilizing poorly water-soluble substances.

[0021] The cyclodextrin used in the tumor cell proliferation inhibitor of the present invention is not particularly limited, and examples thereof include α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and derivatives thereof. Mixtures of these can also be used. Examples of the derivatives include branched cyclodextrins and chemically modified cyclodextrins. Examples of branched cyclodextrins include glycosylated cyclodextrins in which a sugar side chain is attached to cyclodextrin by enzymatic reaction, more specifically, monosaccharide- or disaccharide-modified cyclodextrins such as glucosyl-cyclodextrin, maltosyl-cyclodextrin, galactosyl-cyclodextrin, and mannosyl-cyclodextrin. Examples of chemically modified cyclodextrins include partially methylated cyclodextrin, hydroxypropylated cyclodextrin, sulfobutyl-etherified cyclodextrin, acetylated cyclodextrin, and monochlorotriazinyl-cyclodextrin. In the present invention, it is preferable to use α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin, with α-cyclodextrin or γ-cyclodextrin being particularly preferred.

[0022] Mannose and cyclodextrin may be simply mixed or blended together, or a composition containing mannose and cyclodextrin may be obtained by adding a 5 to 30% aqueous solution or suspension of cyclodextrin to an aqueous solution or powder of mannose and stirring at room temperature or with heating for several minutes to several tens of hours. The composition obtained here is in the form of an aqueous solution, but it may also be powdered by freeze-drying, spray-drying, dehydration, or other methods. Furthermore, the powdered composition may be granulated as needed.

[0023] The amounts of mannose and cyclodextrin to be used can be determined in a manner that is convenient for product design, but generally, it is preferable that the amount of cyclodextrin be 1 to 900 parts by weight, more preferably 10 to 400 parts by weight, and even more preferably 110 to 300 parts by weight, per 100 parts by weight of mannose.

[0024] 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. 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. [Example]

[0028] The present invention will be specifically explained by the following examples, but the present invention is not limited to these examples.

[0029] <Production of mannose derived from konjac root> 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.

[0030] <Production of mannose derived from palm kernel meal> To 10 g of palm kernel meal (Cargill), 22 mL of water and 8 mL of 1 M sulfuric acid were added, and the pH was adjusted to 0.9. The mixture was then prehydrolyzed at 90°C for 4 hours. After cooling, 3 mL of 1 M sodium hydroxide was added to adjust the pH to 3.6, followed by suction filtration and washing with 50 mL of water. The washed palm kernel meal was recovered, and 24 mL of water and 1 M sulfuric acid were added to adjust the pH to 3.6. 0.03 g of the enzyme cellulosin GM5 (HBI, mannanase, unit count: 10,000 units / g) was added. The mixture was shaken at 60°C for 48 hours to allow the enzyme reaction to proceed, followed by inactivation at 100°C for 10 minutes. The resulting raw sugar solution was filtered through activated carbon to obtain the filtrate.

[0031] The obtained filtrate was desalted using 10 mL of a strongly acidic cation exchange resin (Mitsubishi Chemical: PK216) and 10 mL of a weakly basic anion exchange resin (Mitsubishi Chemical: WA30), and then concentrated under reduced pressure using an evaporator. The obtained crude product was crystallized with ethanol to obtain powdered mannose. The obtained powdered mannose was dissolved in water and measured using the following method. The purity of the mannose in this powder was found to be 99%. (Method for measuring the purity of mannose) Equipment: Differential refractive index detector (SHIMADZU Prominence) Column: Aminex HPX-87P (BIO RAD, 300 mm L x 7.8 mm ID) Mobile phase: water, flow rate: 0.6 ml / min, column temperature: 60°C Sample concentration: 5% aqueous solution, sample volume: 10 μL

[0032] (Example 1 and Example 2) A 500 mL beaker was charged with 40 g of γ-cyclodextrin (CycloChem) and 200 g of ion-exchanged water, and after complete dissolution, 60 g of the konjac-derived mannose sugar solution (60 g x 40 g / 100 g = 24 g mannose) was added and stirred for 1 hour using a magnetic stirrer. The resulting solution was then placed in a freeze dryer and dried. Next, using colon cancer spheroids (HC73T strain, owned by Kyoto University), the reactivity of the konjac-derived mannose and γ-cyclodextrin composition obtained above was evaluated by image analysis. All experiments were performed three times independently. Colon cancer spheroids were derived from colon cancer patients. The frozen spheroids 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 composition of konjac root-derived mannose and γ-cyclodextrin obtained above was added to the culture medium so that the mannose concentration was 5 mM (Example 1) or 25 mM (Example 2). The day after seeding was designated Day 0, and on Day 3, images were taken using a Cell3 imager duos (SCREEN Holdings, model CC-8000, software ver. 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 continuous cross-sectional images were acquired at 15 points every 50 μm along the z-axis, and output as fully in-focus images. The reaction was initiated on Day 0 by changing the medium. After that, culturing continued without changing the medium until the end of the experiment. The imaging intervals were kept approximately constant.The Measure function of the analysis software [SCREEN Holdings, Software ver. 1.6 Rev. 2.0.1] was used to apply the program to the spheroid image data to calculate area values. 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, calculate the sphere volume from the radius value, and calculate 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 (Example 1) and Figure 2 (Example 2). Note that GEI on the vertical axis in the figure stands for growth effect index.

[0033] (Comparative Example 1, Comparative Example 3) The same tests were conducted using colon cancer spheroids as in Examples 1 and 2, except that the konjac-derived mannose and γ-cyclodextrin compositions were replaced with γ-cyclodextrin alone. The results are shown in Figure 1 (Comparative Example 1) and Figure 2 (Comparative Example 3).

[0034] (Comparative Example 2, Comparative Example 4) The same test was carried out using colon cancer spheroids, except that the konjac-derived mannose and gamma-cyclodextrin composition of Example 1 was replaced with 5 mM (Comparative Example 2) and 25 mM (Comparative Example 4) of konjac-derived mannose alone. The results are shown in Figure 1 (Comparative Example 2) and Figure 2 (Comparative Example 4).

[0035] As is clear from the results of Figures 1 and 2, when the tumor cell proliferation inhibitory effects of Example 1, Comparative Example 1, and Comparative Example 2 were compared, it was observed that the composition of konjac-derived mannose and gamma-cyclodextrin in Example 1 had a stronger tumor cell proliferation inhibitory effect than either of them administered alone. Furthermore, a similar tendency was observed in Example 2 and Comparative Examples 3 and 4, in which the mannose concentration was increased to 25 mM, and it was observed that the composition of konjac-derived mannose and gamma-cyclodextrin had a much stronger tumor cell proliferation inhibitory effect than either of them administered alone.

[0036] Example 3 30 g of α-cyclodextrin (CycloChem) and 300 g of ion-exchanged water were placed in a 500 mL beaker and completely dissolved. 20 g of the palm kernel meal-derived mannose powder obtained above was then added, and stirring was continued for 1 hour using a magnetic stirrer. The resulting solution was placed in a freeze dryer and dried. An identical test was conducted using colon cancer spheroids, except that the composition of konjac yam-derived mannose and γ-cyclodextrin used in Example 2 was replaced with a composition of palm kernel meal-derived mannose and α-cyclodextrin. The results are shown in Figure 3. The concentration of mannose added to the cells was 25 mM.

[0037] (Comparative Example 5) 30 g of dextrin (Pinex No. 2, Matsutani Chemical Co., Ltd.) and 300 g of ion-exchanged water were placed in a 500 mL beaker and completely dissolved. 20 g of the palm kernel meal-derived mannose powder obtained above was then added, and stirring was continued for 1 hour using a magnetic stirrer. The resulting solution was then placed in a freeze dryer and dried. The same test was conducted using colon cancer spheroids as in Example 3, except that the palm kernel meal-derived mannose and α-cyclodextrin composition used in Example 3 was replaced with a palm kernel meal-derived mannose and dextrin composition. The results are shown in Figure 3. The concentration of mannose added to the cells was 25 mM.

[0038] (Comparative Example 6) The same test was carried out using colon cancer spheroids as in Example 3, except that the palm kernel meal-derived mannose and α-cyclodextrin composition was replaced with the palm kernel meal-derived mannose prepared above. The results are shown in Figure 3. The concentration of mannose added to the cells was 25 mM.

[0039] As is clear from the results in Figure 3, when the tumor cell proliferation inhibitory effects of Example 3, Comparative Examples 5, and 6 were compared, the palm kernel meal-derived mannose and α-cyclodextrin composition of Example 3 was observed to have a stronger tumor cell proliferation inhibitory effect than the palm kernel meal-derived mannose and dextrin composition or palm kernel meal-derived mannose alone. The mannose and cyclodextrin composition was observed to have a much stronger tumor cell proliferation inhibitory effect than either of them alone or compositions other than cyclodextrin. Therefore, effects can be expected even with small doses. Furthermore, the use of mannose derived from natural products allows for safe ingestion or administration.

Claims

1. A tumor cell growth inhibitor for use in the prevention and / or treatment of cancer, comprising mannose and cyclodextrin.

2. 2. The tumor cell proliferation inhibitor according to claim 1, wherein the mannose is derived from at least one 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.

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