Use of norethynodrel heptanoate compounds in the prevention or treatment of cancer

Abstract

The present invention relates to the use of norethynodrel heptanoate, a stereoisomer, a hydrate, a solvate or a salt thereof. In particular, norethynodrel heptanoate, a stereoisomer, a hydrate, a solvate or a salt thereof is effective for the prevention, amelioration or treatment of cancer.

Description

Technical Field

[0001] This invention relates to the use of a heptaacetic acid norethindrone compound in the prevention or treatment of cancer. Background Technology

[0002] Norethisterone enanthate, or norethisterone enanthate, is used as a contraceptive and is marketed under the brand name Noristerat (Tenhaeff, D., et al., "3-month contraception with norethisteron"). "Norethindrone heptaate. Clinical and biochemical studies." Die Medizinische Welt 40 (1971): 1551-1553).

[0003] Cancer is an abnormal population of cells that proliferates due to a disruption of the balance between cell division and apoptosis caused by various factors. It is also known as a tumor or growth. Cancer typically occurs in more than 100 parts of the body, including organs, white blood cells, bones, and lymph nodes, and develops into serious symptoms by infiltrating surrounding tissues and metastasizing to other organs. To date, various anticancer drugs have been developed, but the development of an effective anticancer drug that can inhibit the proliferation of cancer cells remains a priority.

[0004] Therefore, the inventors devoted themselves to the research of developing novel anticancer drugs, and as a result confirmed that norethindrone heptaate has the effects of inhibiting the proliferation and apoptosis of various cancer cells, thus completing the present invention. Summary of the Invention

[0005] Technical issues One object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of cancer, comprising norethindrone heptanate, its stereoisomer, hydrate, solvate or salt.

[0006] Another object of the present invention is to provide a health food for the prevention or improvement of cancer, comprising norethindrone heptanate, its stereoisomers, hydrates, solvates or salts.

[0007] Another object of the present invention is to provide a method for preventing or treating cancer, comprising the step of administering norethindrone heptaate, its stereoisomer, hydrate, solvate or salt to a desired individual.

[0008] Another object of the present invention is to provide a feed composition for the prevention or improvement of cancer, comprising norethindrone heptanate, its stereoisomer, hydrate, solvate or salt.

[0009] Another object of the present invention is to provide the use of norethindrone heptaate or its stereoisomers, hydrates, solvates or salts in the prevention or treatment of cancer.

[0010] Another object of the present invention is to provide the use of norethindrone heptaate or its stereoisomers, hydrates, solvates or salts in the preparation of medicaments for the prevention or treatment of cancer.

[0011] Technical solution The various descriptions and embodiments disclosed in this application can also be applied to other descriptions and embodiments. That is, all combinations of the various elements disclosed in this application fall within the scope of this invention. Furthermore, the scope of this invention should not be considered limited by the specific descriptions below.

[0012] One aspect of this application is a pharmaceutical composition for the prevention or treatment of cancer, comprising norethindrone heptaate, its stereoisomer, hydrate, solvate, or salt.

[0013] The chemical formula of norethindrone heptaate is as follows: Figure 1 As shown.

[0014] The term "stereoisomer" refers to compounds with the same molecular formula but different atomic arrangements or spatial configurations. Isomers include, for example, structural isomers and stereoisomers. A stereoisomer can be a diastereomer or an enantiomer. An enantiomer is an isomer that is not a mirror image of its counterpart, like the relationship between the left and right hands; it is also called an optical isomer. When the four substituents attached to the chiral central carbon atom are all different, enantiomers are distinguished by R (rectus: clockwise) and S (sinister: counterclockwise). A diastereomer is a stereoisomer that is not a mirror image of its counterpart; due to different atomic spatial arrangements, the resulting cis-trans isomers can be classified accordingly.

[0015] A solvate is a compound that dissolves in organic or inorganic solvents. A solvate may be, for example, a hydrate.

[0016] The term "salt" refers to a salt that can be prepared in the same reaction system during the final separation, purification, and synthesis of a compound according to an embodiment of the invention, or prepared separately by reacting with an inorganic or organic base. For said salt, when the compound of the invention contains an acidic group, it can form a salt with a base. Such salts are not limited to this, but may include: for example, salts with alkali metals, such as lithium, sodium, or potassium salts; salts with alkaline earth metals, such as barium or calcium; salts with other metals, such as magnesium salts; organic base salts, such as salts with dicyclohexylamine; and salts with basic amino acids, such as lysine or arginine. Furthermore, when the compounds of the present invention contain a basic group in the molecule, they can form acid addition salts. Examples of such acid addition salts are not limited to those listed here, but may include: salts with inorganic acids, particularly with hydrohalic acids (e.g., hydrofluoric acid, hydrobromic acid, hydroiodic acid, or hydrochloric acid), nitric acid, carbonic acid, sulfuric acid, or phosphoric acid; salts with lower alkyl sulfonic acids, such as methanesulfonic acid, trifluoromethanesulfonic acid, or ethanesulfonic acid; salts with benzenesulfonic acid or p-toluenesulfonic acid; salts with organic carboxylic acids, such as acetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid, or citric acid; and salts with amino acids, such as glutamic acid or aspartic acid.

[0017] The term "cancer" refers to a group of diseases characterized by the production of abnormal cells that proliferate uncontrollably and have the ability to invade and destroy normal body tissues. In one specific example, the cancer can be a solid tumor or a hematologic malignancy. Specifically, the solid tumor is selected from any one or more of the following groups: breast cancer, lung cancer, prostate cancer, ovarian cancer, brain cancer, liver cancer, cervical cancer, endometrial cancer, uterine cancer, colon cancer, colorectal cancer, rectal cancer, kidney cancer, nephroblastoma, skin cancer, oral squamous cell carcinoma, epidermal carcinoma, nasopharyngeal carcinoma, head and neck cancer, bone cancer, esophageal cancer, bladder cancer, lymphangiocarcinoma, gastric cancer, pancreatic cancer, testicular cancer, thyroid cancer, thyroid follicular carcinoma, melanoma, myeloma, multiple myeloma, mesothelioma, osteosarcoma, myelodysplastic syndrome, mesenchymal tumor, soft tissue sarcoma, liposarcoma, gastrointestinal stromal tumor, malignant peripheral nerve sheath tumor, Ewing sarcoma, leiomyosarcoma, mesenchymal chondrosarcoma, lymphosarcoma, fibrosarcoma, rhabdomyosarcoma, teratoma, etc. Fetal cancer, neuroblastoma, medulloblastoma, glioma, benign skin tumors, leukemia, brain tumors, benign astrocytoma, malignant astrocytoma, pituitary adenoma, meningioma, brain lymphoma, oligodendroglioma, ependymoma, brainstem tumors, laryngeal cancer, oropharyngeal cancer, nasal cavity / sinus cancer, nasopharyngeal cancer, salivary gland cancer, hypopharyngeal cancer, thyroid cancer, oral cancer, thoracic tumors, small cell lung cancer, non-small cell lung cancer, thymic carcinoma, mediastinal tumors, esophageal cancer, male breast cancer, abdominal tumors, gallbladder cancer, bile duct cancer, small intestine cancer, large intestine cancer, anal cancer, male genital tumors, penile cancer, female genital tumors, ovarian cancer, uterine sarcoma, vaginal cancer, female external genital cancer, female urethral cancer, bone tumors, duodenal cancer, and fibrosarcoma, but not limited to these. The blood cancer is selected from any one or more of the following groups: acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, acute monocytic leukemia, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma, but is not limited thereto.

[0018] The term "prevention" can refer to all actions that suppress an individual's cancer or delay its onset by administering a pharmaceutical composition according to a regimen.

[0019] The term "treatment" can refer to all actions that improve or benefit cancer symptoms by administering a drug composition according to a regimen.

[0020] In one specific example, the pharmaceutical composition may not cause the side effect of weight gain or loss, but is not limited thereto.

[0021] When the pharmaceutical composition is formulated, it can be prepared using commonly used lubricants, sweeteners, flavorings, emulsifiers, suspending agents, preservatives, fillers, extenders, binders, wetting agents, disintegrants, surfactants, and other diluents or excipients.

[0022] Solid dosage forms for oral administration may include tablets, pills, powders, granules, capsules, etc. These solid dosage forms can be formulated by mixing any one or more excipients such as starch, calcium carbonate, sucrose or lactose, gelatin, etc., with the composition. In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Liquid dosage forms for oral administration include suspensions, oral solutions, emulsions, syrups, etc. Besides commonly used simple diluents such as water and liquid paraffin, various excipients may be included, such as wetting agents, sweeteners, flavoring agents, preservatives, etc.

[0023] Formulations intended for non-oral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, injections, suppositories, etc. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. The base for suppositories may include witepsol, polyethylene glycol, Tween 61, cocoa butter, lauryl resin, glycerin gelatin, etc., and when formulated as eye drops, known diluents or excipients may be used. Injectable formulations may include subcutaneous injections, intradermal injections, intravenous injections, intramuscular injections, intraperitoneal injections, or intravenous infusions. Injectable formulations may be prepared using aqueous solvents such as physiological saline and Ringer's solution, and solvents such as vegetable oils, higher fatty acid esters (e.g., ethyl oleate), or alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.). Injectable formulations may include biocompatible substances for sustained drug release (e.g., hyaluronic acid, collagen, PLGA, chitosan, etc.), stabilizers to prevent deterioration (e.g., ascorbic acid, sodium bisulfite, sodium metabisulfite, BHA, tocopherol, EDTA, etc.), emulsifiers, buffers to adjust pH, or preservatives to inhibit microbial growth (e.g., phenylmercuric nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.) and other drug carriers.

[0024] The pharmaceutical composition may be provided in combination with existing known compositions for the prevention or treatment of cancer or other existing anticancer drugs, which may be existing known compositions for the prevention or treatment of cancer, existing anticancer drugs or newly developed anticancer drugs.

[0025] When the pharmaceutical composition contains other anticancer drugs with cancer prevention or treatment effects, it is important to mix an amount that can achieve the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

[0026] When the pharmaceutical composition also contains other anticancer drugs, it can produce a more significant synergistic effect in terms of anticancer effects (i.e., tumor growth inhibition, immune activity, etc.).

[0027] In one specific example, the routes of administration of the pharmaceutical composition include, but are not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, local, sublingual, or rectal.

[0028] The composition can be administered orally or non-orally. When not administered orally, it can be administered via topical skin, intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, or intrapleural injection.

[0029] The pharmaceutical composition is administered at a pharmaceutically effective amount. The term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment. The effective dose level can be determined based on factors including the type and severity of the patient's disease, the activity of the drug, the patient's sensitivity to the drug, the time of administration, the route of administration and excretion rate, the duration of treatment, concomitant drugs, and other factors known in the medical field.

[0030] Specifically, the effective amount of the pharmaceutical composition can vary depending on the patient's age, gender, condition, weight, absorption rate, inactivation rate, excretion rate of the active ingredient in the body, type of disease, and concurrent medications, and can be increased or decreased according to the route of administration, severity of obesity, gender, weight, age, etc.

[0031] Another aspect of this application is a method for preventing or treating cancer, comprising the step of administering to a desired individual a composition comprising norethindrone heptaate, its stereoisomers, hydrates, solvates or salts; or a composition comprising the same.

[0032] The terms "stereoisomer", "hydrate", "solvent", "salt", "cancer", "prevention", and "treatment" can be within the aforementioned scope.

[0033] The term "individual" refers to the object on which the compositions of the present invention can be administered (prescribed), which may be an individual who has or may have cancer.

[0034] Furthermore, the term "individual" can refer to mammals such as rats, mice, and livestock, including humans, but is not limited to these.

[0035] Another aspect of this application is a health food for the prevention or improvement of cancer, comprising norethindrone heptaate, its stereoisomers, hydrates, solvates, or salts.

[0036] The terms "stereoisomer", "hydrate", "solvent", "salt", "cancer", and "prevention" can be within the aforementioned scope.

[0037] The term "improvement" can refer to all behaviors that at least reduce parameters associated with the treated state, such as the severity of symptoms. In this context, the health food product can be used, either concurrently with or alone, with a medication for treatment, before or after the onset of the disease to prevent or improve cancer.

[0038] In the aforementioned health functional foods, the active ingredients can be added directly to the food or used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredients can be appropriately determined according to its intended use (for prevention or improvement).

[0039] The health functional foods also include one or more of the following: carriers, diluents, excipients, and additives, and can be formulated into one of the following dosage forms: tablets, pills, powders, granules, capsules, and liquids. Foods that may contain compounds according to a scheme include various food categories, powders, granules, tablets, capsules, syrups, beverages, chewing gum, tea, vitamin complexes, and health functional foods.

[0040] Specific examples of the carrier, excipient, diluent, and additive are at least one selected from the group consisting of: lactose, glucose, sucrose, sorbitol, mannitol, erythritol, starch, gum arabic, calcium phosphate, alginate, gelatin, calcium phosphate, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, polyvinylpyrrolidone, methylcellulose, water, syrup, methylcellulose, methylparaben, propylparaben, talc, magnesium stearate, and mineral oil.

[0041] In addition to the aforementioned active ingredients, the health functional food may contain other ingredients as essential components without particular limitation. For example, like ordinary beverages, it may contain various flavoring agents or natural carbohydrates as additional ingredients. Examples of natural carbohydrates may be monosaccharides, such as glucose and fructose; disaccharides, such as maltose and sucrose; and polysaccharides, such as dextrin and cyclodextrin; as well as sugar alcohols such as xylitol, sorbitol, and erythritol. As flavor enhancers other than those mentioned above, natural flavor enhancers (such as sematriene and stevia extract (e.g., rebaudioside A, glycyrrhizic acid, etc.)) and synthetic flavor enhancers (such as saccharin and aspartame) may be advantageously used. The proportion of the natural carbohydrates can be appropriately determined by those skilled in the art.

[0042] In addition to the above, the health functional food according to one embodiment may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavoring agents, coloring agents and flavor enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, and carbonating agents used in carbonated beverages. These components may be used alone or in combination, and the proportions of these additives may be appropriately selected by those skilled in the art.

[0043] Another aspect of this application is a feed composition for the prevention or improvement of cancer, comprising norethindrone heptaate, its stereoisomer, hydrate, solvate, or salt.

[0044] The terms "stereoisomer", "hydrate", "solvent", "salt", "cancer", "prevention", and "improvement" can be within the aforementioned scope.

[0045] The term "feed" refers to any natural or artificially formulated food, meal, or component of a meal that is intended for or suitable for the consumption, ingestion, and digestion of animals. Specifically, the feed composition according to the invention for the prevention or improvement of cancer can be prepared using various forms of feed known in the art, preferably including concentrated feed, roughage, and / or specialty feed.

[0046] Concentrated feeds include, but are not limited to: grains, including cereals such as wheat, oats, and corn; bran, a byproduct obtained after grain refining, including rice bran, wheat bran, and barley bran; oilseed meal, a byproduct obtained after pressing soybeans, rapeseed, sesame, flaxseed, and coconut; residue, the residue after extracting starch from sweet potatoes, potatoes, etc.—residual starch as the main component of starch residue; animal feeds, fishmeal, fish residue, fish soluble (a concentrate of fresh liquid extracted from fish), meat meal, blood meal, feather meal, skim milk powder, and whey (residue from making cheese from milk and casein from skim milk); yeast, chlorella, and seaweed.

[0047] Roughage includes, but is not limited to: wild grasses, pasture grasses, freshly cut green grasses, and other green fodder; root vegetables such as forage turnips, forage beets, and rutabagas; silage, which is stored feed made by filling silage pits with fresh grasses, freshly cut crops, and grains for lactic acid fermentation; hay, which is made by drying harvested wild grasses and pasture grasses; cereal crop stalks; and leaves of legumes. Specialty feeds include, but are not limited to: mineral feeds, such as oyster shells and rock salt; urea feeds, such as urea and its derivatives such as diurea isobutane; feed additives, which are substances added in trace amounts to compound feeds to supplement components that are easily lacking when only natural feed ingredients are used, or to improve the storage properties of the feed; and dietary supplements.

[0048] The feed composition for preventing or improving cancer can be prepared by adding norethindrone heptaate or its stereoisomers, hydrates, solvates or salts, within an appropriate effective concentration range, according to various feed preparation methods known in the art.

[0049] Another aspect of this application is the use of a norethindrone heptaate or its stereoisomer, hydrate, solvate or salt; or a composition comprising the thereof for the prevention or treatment of cancer.

[0050] Another aspect of this application is the use of norethindrone heptaate or its stereoisomers, hydrates, solvates or salts; or compositions comprising the thereof in the preparation of medicaments for the prevention or treatment of cancer.

[0051] Invention Effects This invention establishes the effects of inhibiting cancer cell proliferation and increasing cancer cell apoptosis by treating cancer cells with norethindrone heptanate. Norethindrone heptanate can be effectively used to develop anticancer therapeutic agents that inhibit cancer cell growth and induce apoptosis. Attached Figure Description

[0052] Figure 1 A diagram showing the structure of norethindrone heptaate.

[0053] Figure 2 This is a graph showing the survival rate of HepG2 cells after treatment with norethindrone heptaate.

[0054] Figure 3 This is a graph showing the survival rate of H1975 cells after treatment with norethindrone heptaate.

[0055] Figure 4 This is a graph showing the survival rate of PC-3 cells after treatment with norethindrone heptaate.

[0056] Figure 5 This is a graph showing the survival rate of HCT116 cells after treatment with norethindrone heptaate.

[0057] Figure 6The figure shows the changes in tumor volume in mice xenografted with HCT116, based on norethindrone heptaate treatment.

[0058] Figure 7 The graph shows the changes in body weight in mice xenografted with HCT116 based on norethindrone heptaate treatment.

[0059] Figure 8 The figure shows the changes in tumor volume in mice xenografted with HepG2, based on norethindrone heptanate treatment.

[0060] Figure 9 The graph shows the changes in body weight in mice xenografted with HepG2 based on norethindrone heptaate treatment.

[0061] Figure 10 The graphs show the comparative analysis of tumor volume growth in mice xenografted with HepG2, based on treatment with norethindrone heptanate and the anticancer agent sorafenib.

[0062] Figure 11 A graph showing the changes in body weight in mice xenografted with HepG2, based on treatment with norethindrone heptanate and the anticancer agent sorafenib. Detailed Implementation

[0063] The present invention will be described in more detail below through embodiments. However, these embodiments are intended to illustrate the invention, and the scope of the invention is not limited to these embodiments.

[0064] Example Example 1. Cell Culture and Compound Preparation HepG2 cells (human liver cancer cell line), HCT116 cells (human colon cancer cell line), and PC-3 cells (human prostate cancer cell line) were purchased from the Korea Cell Bank (KCLB), and H1975 cells (human non-small cell lung cancer (NSCLC) cell line) were purchased from the American Type Culture Collection (ATCC, Virginia, USA) and were used for experiments.

[0065] HCT116 and HepG2 cells were cultured in RPMI 1640 medium (Rosewell Park Memorial Institute) supplemented with 2 mM glutamine, 1% penicillin-streptomycin and 10% fetal bovine serum (FBS) at 37°C and 5% CO2.

[0066] Norethindrone heptaate was purchased and used from MedChemExpress.

[0067] Example 2. Confirmation of the effect of norethindrone heptaate on reducing cancer cell survival rate. The experiment investigated whether treatment with norethindrone heptaate reduced the survival rate of HepG2, H1975, PC-3, and HCT116 cells.

[0068] Specifically, cells were spaced at 2 to 5 × 10⁶ cells per well. 3 Cells were seeded at a density of 1 / 2 well in 96-well plates and cultured at 37°C for 24 hours before treatment with norethindrone heptanate. Plates treated with different concentrations (0 to 20 μM) of norethindrone heptanate were cultured at 37°C for 72 hours in 5% CO2.

[0069] Subsequently, 100 μL of the test reagent ( Promega was added to each well, and then a microplate reader was used. Microplate reader (Promega) measures luminescence to calculate cell viability (%).

[0070] The results showed that with increasing concentrations of norethindrone heptaate, the cell viability of HepG2, H1975, PC-3, and HCT116 cells all decreased significantly. Figure 2 , 3 (4, 5). Table 1 below shows the IC50 of each cancer cell.

[0071] Table 1

[0072] This confirms that norethindrone heptaate has anti-cancer effects against various cancers.

[0073] Example 3. Confirmation of the tumor growth inhibitory effect of norethindrone heptaate in a mouse xenograft model. To confirm the anticancer effect of norethindrone enanthate in a mouse xenograft model, changes in tumor size were observed. HCT116 and HepG2 cells were injected into the mouse xenograft model, then treated with norethindrone enanthate, and changes in tumor size were measured.

[0074] Specifically, HCT116 cells (1×10⁻⁶) were used. 6 Cellular tissue was subcutaneously transplanted into 6- to 8-week-old male BALB / c nude mice. The average tumor volume reached 100 to 150 mm. 3Mice were then randomly divided into three groups (n=5 per group). Norethindrone enanthate was administered intraperitoneally to mice in the first and second groups at doses of 10 mg / kg (mpk) and 20 mg / kg, respectively, every other day for 14 days. Meanwhile, 100 μL of a solution of DMSO, Tween-80, PEG300, and physiological saline in a volume ratio of 5:5:20:70 was injected intraperitoneally into the remaining group of mice every other day for 14 days. Body weight and tumor diameter were measured every other day, and tumor volume was assessed using calipers according to the following formula [Equation 1]: [Mathematical Expression 1] .

[0075] P-values ​​are determined using the Student's t-test.

[0076] HepG2 cells (1.5 × 10⁻⁶) 6 Cellular tissue was subcutaneously transplanted into 6- to 8-week-old male BALB / c nude mice. The average tumor volume reached 50 mm. 3 Mice were then randomly divided into three groups (n=6 per group). Norethindrone enanthate was administered intraperitoneally to the mice in the first two groups at doses of 10 mg / kg and 20 mg / kg daily for 10 days. Meanwhile, 100 μL of a solution of DMSO, Tween-80, PEG300, and physiological saline in a volume ratio of 5:5:20:70 was injected intraperitoneally into the remaining group of mice daily for 10 days. Body weight and tumor diameter were measured every other day, and tumor volume was assessed using calipers according to the formula described in [Equation 1]. P-values ​​were determined using a Student's t-test. Animal experimental procedures were performed in accordance with the guidelines approved by the Ersteq Co., Ltd. Animal Management and Use Committee.

[0077] The results confirmed that, compared with the control group, norethindrone enanthate inhibited tumor growth in a concentration-dependent manner in mouse xenograft models of HCT116 cells and HepG2 cells. Figure 6 and Figure 8 Furthermore, it was confirmed that the body weight of mouse xenograft models of HCT116 and HepG2 cells remained constant during administration of norethindrone enanthate. Figure 7 and Figure 9 ).

[0078] This confirms that norethindrone heptaate can inhibit tumor growth in animal models, thus exhibiting anti-cancer effects.

[0079] Example 4. Confirmation of superior tumor growth inhibition effect compared to existing anticancer drugs To confirm whether norethindrone enanthate has superior anticancer effects compared to existing anticancer drugs, changes in tumor size were compared. HepG2 cells were injected into a mouse xenograft model, then treated with norethindrone enanthate, and changes in tumor size were measured.

[0080] Specifically, HepG2 cells (3 × 10⁻⁶) 6 Cellular tissue was subcutaneously transplanted into 6- to 8-week-old female BALB / c nude mice. The average tumor volume reached 50 to 100 mm. 3 Mice were then randomly divided into four groups (n=6 per group). Norethindrone enanthate was administered intraperitoneally to two groups of mice daily at doses of 10 mg / kg and 20 mg / kg, respectively. Sorafenib was administered intraperitoneally to one group daily at a dose of 20 mg / kg. The remaining group was administered 100 μL of the same vehicle as in Example 3 daily for 14 days via intraperitoneal injection. Body weight and tumor diameter were measured every other day, and tumor volume was assessed using calipers according to the formula described in [Mathematical Formula 1]. P-values ​​were determined using a Student's t-test. Animal experimental procedures were performed in accordance with guidelines approved by the Ersteq Co., Ltd. Animal Management and Use Committee.

[0081] The results showed that in mouse xenograft models without norethindrone enanthate treatment, tumor size continued to increase, while in mouse xenograft models treated with norethindrone enanthate treatment, tumor size showed a continuous decreasing trend. Figure 10 Furthermore, norethindrone enanthate reduced tumor size in a concentration-dependent manner, and compared with the existing anticancer drug sorafenib, it significantly reduced tumor size. Figure 10 During administration of norethindrone heptaate, the body weight of the mouse xenograft model remained constant. Figure 11 ).

[0082] This confirms that norethindrone heptaate has a superior anticancer effect compared to the existing anticancer drug sorafenib.

[0083] The above description of the present invention is for illustrative purposes only. Those skilled in the art should understand that the present invention can be readily modified into other specific forms without altering its technical concept or essential features. Therefore, it should be understood that all aspects of the described embodiments are exemplary and not restrictive.

Claims

1. A pharmaceutical composition for the prevention or treatment of cancer, characterized in that, It includes norethindrone heptaate, its stereoisomers, hydrates, solvates, or salts.

2. The pharmaceutical composition according to claim 1, characterized in that, The pharmaceutical composition does not cause any side effects such as weight gain or loss.

3. The pharmaceutical composition according to claim 1, characterized in that, The cancer in question is a solid tumor.

4. The pharmaceutical composition according to claim 1, characterized in that, The cancer in question is a blood cancer.

5. The pharmaceutical composition according to claim 3, characterized in that, The solid tumor is selected from any one or more of the following groups: breast cancer, lung cancer, prostate cancer, ovarian cancer, brain cancer, liver cancer, cervical cancer, endometrial cancer, uterine cancer, colon cancer, colorectal cancer, rectal cancer, kidney cancer, nephroblastoma, skin cancer, oral squamous cell carcinoma, epidermal carcinoma, nasopharyngeal carcinoma, head and neck cancer, bone cancer, esophageal cancer, bladder cancer, lymphangiocarcinoma, gastric cancer, pancreatic cancer, testicular cancer, thyroid cancer, thyroid follicular carcinoma, melanoma, myeloma, multiple myeloma, mesothelioma, osteosarcoma, myelodysplastic syndrome, mesenchymal tumors, soft tissue sarcoma, liposarcoma, gastrointestinal stromal tumors, malignant peripheral nerve sheath tumors, Ewing's sarcoma, leiomyosarcoma, mesenchymal chondrosarcoma, lymphosarcoma, fibrosarcoma, rhabdomyosarcoma. Teratoma, neuroblastoma, medulloblastoma, glioma, benign skin tumors, leukemia, brain tumors, benign astrocytoma, malignant astrocytoma, pituitary adenoma, meningioma, brain lymphoma, oligodendroglioma, ependymoma, brainstem tumors, laryngeal cancer, oropharyngeal cancer, nasal / sinus cancer, nasopharyngeal cancer, salivary gland cancer, hypopharyngeal cancer, thyroid cancer, oral cancer, thoracic tumors, small cell lung cancer, non-small cell lung cancer, thymic carcinoma, mediastinal tumors, esophageal cancer, male breast cancer, abdominal tumors, gallbladder cancer, bile duct cancer, small intestine cancer, large intestine cancer, anal cancer, male genital tumors, penile cancer, female genital tumors, ovarian cancer, uterine sarcoma, vaginal cancer, female external genital cancer, female urethral cancer, bone tumors, duodenal cancer, and fibrosarcoma.

6. The pharmaceutical composition according to claim 4, characterized in that, The blood cancer is selected from any one or more of the following groups: acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, acute monocytic leukemia, multiple myeloma, Hodgkin lymphoma, and non-Hodgkin lymphoma.

7. A health food product for preventing or improving cancer, characterized in that, It includes norethindrone heptaate, its stereoisomers, hydrates, solvates, or salts.

8. A feed composition for the prevention or improvement of cancer, characterized in that, It includes norethindrone heptaate, its stereoisomers, hydrates, solvates, or salts.

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