KR20130021202A - Composition for anti cancer comprising extract from hoo bak - Google Patents

Abstract

PURPOSE: An anticancer composition containing a silver magnolia extract is provided to specifically suppress BAF phosphorylation using VRK1 phosphoenzyme. CONSTITUTION: An anticancer composition contains one or more ingredients selected from the group consisting of a silver magnolia extract, a compound isolated from the extract, and a derivative of the compound as active ingredients. The extract is prepared by extracting silver magnolia fruit with one or more organic solvents selected from the group consisting of n-hexane, ethyl acetate, n-butanol, and methanol.

Description

TECHNICAL FIELD [0001] The present invention relates to an anticancer composition comprising an extract of Lilac,

The present invention relates to an anticancer composition, and more particularly, to an anticancer composition comprising a natural-substance-derived substance having a binding property between VRK1 (Vaccina-related kinase 1) and a BAF protein and an inhibitory activity against BAF phosphorylation .

There are two types of chemotherapeutic drugs: conventional chemotherapeutic agents that induce DNA damage or alter the structure of the tubulin protein, and molecular targeting drugs that target certain genes to treat cancer. In general, the chemotherapeutic technique used in the treatment of cancer was based on surgical therapy and radio therapy (Radio radiation). Recently, however, traditional chemotherapy is becoming a new phase of targeted chemotherapy. Targeted therapy or tailor-made drugs are targeted at specific genes, or even polymorphisms of specific genes. This is largely different from drugs that target existing dividing cells. This type of study is now expected to be of great help in many types of chemotherapy.

Given the concept of targeted chemotherapy, screening genes that may be targets of small molecule inhibitors or monoclonal antibodies is a very important and fundamental problem. Today, most related chemotherapeutic agents target receptor tyrosine kinases, or mitotic kinases, that are present on the cell surface.

Recently, the gene related to the cell cycle has also attracted attention of many researchers. Unlike extracellular growth factor receptors or secretory proteins, genes within the cell associated with the cell cycle are often the starting point of cancer cell formation, and thus, unlike conventional targets, they are likely to be more reliable target drugs Big.

However, the target gene of the existing target or the new drug being developed is causing a lot of side effects due to the multifaceted nature of the cell, which plays a structural part or participates in various physiological phenomena. In addition, existing small molecule inhibitors often have problems such as biocompatibility and target orientation. In particular, given the global trend of developing targeted drugs, there are few papers presenting new drug targets in Korea, and it is very rare to report drugs that target specific genes.

VRK1 plays a different role depending on the cell cycle, and seems to perform a key function, especially in the outgrowth of G0. This result is based on the immediate reaction when added with serum, and is due to similar actions to MYC and FOS which are similar early reaction genes. In particular, c-Jun, ATF2, and p53, which must be phosphorylated at the beginning of the cell cycle, are well known substrates for VRK1. This is an indirect indication that VRK1 is an essential factor in the progression of the cell cycle. As one of the more stable proteins, VRK1 phosphorylates p53 in response to DNA damage. In addition, VRK1 phosphorylates Thr3 and Ser10 of histone protein H3 in the latter half of the cell cycle, and plays a crucial role in the chromosome segregation by condensing the chromosomes into chromosomes. In addition, phosphorylation of the nuclear membrane protein, BAF, It plays an important role in reshaping.

In this regard, it is urgent to select a new type of targeted cancer therapy that surpasses the existing technical limitations, and it can be seen that a drug targeting VRK1 can be an alternative.

SUMMARY OF THE INVENTION Accordingly, the present invention has been made in order to solve the above problems of the prior art, and it is an object of the present invention to provide an anticancer agent which is free from the risk of side effects or toxicity of a conventional chemotherapeutic agent, And a process for producing the same.

In order to accomplish the above object, the present invention provides an anticancer composition comprising as an active ingredient at least one member selected from the group consisting of achene extract, a compound isolated from the acacia var. Umbraculifera extract, and derivatives of the compound.

Hereinafter, the present invention will be described in more detail.

The present inventors conducted an activity investigation step using a large-scale plant library made up of various plants treated as herbal medicines and medicinal agricultural products in order to find a natural substance suitable for targeted chemotherapy. As a result, It was confirmed that the extracted substance specifically inhibited BAF phosphorylation by VRK1 phosphorylase, which has a crucial effect on tumor formation, thus completing the present invention.

The VRK1 is essential for the progression of the cell cycle, and it phosphorylates the nuclear membrane protein, BAF, and plays an important role in decomposition and regeneration of the nuclear membrane during the cell division. Accordingly, the extract of the present invention that specifically inhibits BAF phosphorylation-related signaling by VRK1 can be effectively used for a novel type of targeted chemotherapeutic treatment.

Specific diseases to which the anticancer composition of the present invention can be applied include various cancers such as, for example, head and neck squamous cell carcinoma, lung cancer, colon cancer or blood cancer, and preferably squamous cell cancer or blood cancer.

Accordingly, one embodiment of the present invention provides an anticancer composition comprising at least one selected from the group consisting of a capsaicin extract, a compound separated from the capsaicin extract, and a derivative of the compound as an active ingredient, and a method for producing the same.

As used herein, " treatment " is intended to include alleviation or amelioration of symptoms, reduction in the extent of disease, delay or alleviation of disease progression, improvement, alleviation or stabilization of disease states, partial or complete recovery, Is used to mean both.

Also, in the present specification, the term "backbone extract" means a product obtained by extracting from various outposts such as leaves, flowers, stems and roots, and preferably obtained from the bark of Japanese apricot.

Also, in the present specification, the weight of the backbone extract or its fractions is based on the dry weight of the backbone extract or the fractions thereof in the absence of the solvent.

The magnolia is flowering plants as belonging to the dicotyledon steel door magnoliales lauraceae, magnolia (Machilus thunbergii ), perch ( Magnolia officinalis ) or Japanese magnolia ( Magnolia obovata ) can be used.

Preferably, the backbone extract, the compound separated from the backbone extract, or the derivative of the compound may inhibit the formation or development of cancer through inhibition of phosphorylation of BAF, a substrate of VRK1.

The albumen extract may be an organic solvent extract which is preferably extracted with at least one organic solvent selected from the group consisting of n -hexane, EtOAC (ethyl acetate), n- BuOH ( n -butanol), and MeOH (methanol).

The amount of the organic solvent to be used is not particularly limited and may be, for example, 3 to 5 times the weight of the final product.

Wherein the Magnolia extract is preferably n in accordance with the polarity of the organic solvent extract - with butanol (n -BuOH) 1 Fraction solvent more member selected from the group consisting of hexane (n -hexane), ethyl acetate (EtOAc), and n The fraction may be at least one fraction selected from the group consisting of n-hexane fraction, ethyl acetate fraction and n-butanol fraction, and more preferably n-hexane fraction or n-butanol fraction.

The compound isolated from the albumen extract or the derivative of the compound may be represented by the following general formula (4).

In Chemical Formula 4,

R ₁ is hydrogen and R ₂ is a C ₁₃ to C ₁₇ straight chain hydrocarbon group which is saturated or unsaturated by one or five double bonds.

Preferably, R ₂ is a C ₁₃ to C ₁₇ straight chain hydrocarbon group which is unsaturated by one or two double bonds.

Also, preferably, the compound isolated from the albumen extract may be a compound of the following formula (1) or (3), more preferably a compound of the following formula (1).

The anticancer composition preferably contains at least one member selected from the group consisting of the above-described extract of Bean curd, the compound separated from the beetle extract, and derivatives of the above compound in an amount of 0.0001 to 99.9% by weight, May be contained in an amount of 0.1 to 99% by weight.

Also, the anticancer composition may further comprise an appropriate carrier, excipient, diluent and the like conventionally used in the production of the anticancer composition.

The carrier, excipient and diluent may be, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, Polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and the like.

The anticancer composition may be administered orally or parenterally according to a conventional method. For example, when the composition is orally administered, it may be formulated into powders, granules, tablets, suspensions, emulsions and syrups.

The preferred dosage amount may be a content suitable for the treatment or prevention of the subject and / or disease, including the age, sex, general health and weight of the subject, the kind and severity of the disease, the type of formulation, The type and content of the other components, the proportion of the composition, the route and the duration of administration, and the like, and may be appropriately selected by those skilled in the art.

The subject to be administered may be a mammal including a human. For the anticancer drug, a preferable effective dose is, for example, 1 or more times in an amount of 20 mg to 40 mg based on 1 kg of adult body weight on the basis of the active ingredient Lt; / RTI > However, the above-mentioned dosage is only for illustrative purposes and is not limited to the above range.

In another embodiment of the present invention, there is provided a process for producing a polyurethane foam, comprising the steps of: 1) adding at least one organic solvent selected from the group consisting of n -hexane, ethyl acetate, n -butanol, and methanol; And 2) extracting and filtering the supernatant to which the organic solvent has been added at room temperature to obtain a supernatant extract.

Preferably, the extraction with the organic solvent may be performed at room temperature for 20 to 28 hours, but is not limited thereto.

Preferably, after step 2), 3) separating the filtrate and the residue obtained through the filtration step, and repeating the steps 1) and 2) for the separated residue two to three times .

In addition, the nutmeg extract may be prepared in powder state by collecting the filtrate obtained in step 2) and / or step 3), and further performing the step of concentration under reduced pressure, freeze drying, spray drying and the like.

The amount of the organic solvent to be used is not particularly limited and may be, for example, 3 to 5 times the weight of the final product.

Preferably, after the step of extracting organic solvent, the organic solvent extract is sequentially fractionated with at least one fraction solvent selected from the group consisting of n -hexane, ethyl acetate, and n -butanol in accordance with polarity to obtain n -hexane fraction, Ethyl acetate fraction, and n - butanol fraction. The conditions such as the temperature and the time suitable for the fractionation process can be suitably adjusted by those skilled in the art, but preferably 20 to 35 ° C.

Preferably, the step further comprises, after the sequential fractionation step, concentrating the fractions obtained in the respective sequential fractionation steps and concentrating them under reduced pressure and freeze-drying.

According to the present invention, there is provided an anticancer composition comprising a natural-material-derived substance as an active ingredient and a method for producing the same. The anticancer composition is free from the risk of side effects or toxicity, which is a problem of existing chemotherapeutic agents, and phosphorylates the nuclear membrane protein, BAF, and plays an important role in degradation and reshaping of the nuclear membrane during cell division Can specifically inhibit BAF phosphorylation by VRK1 phosphorylase, which has a crucial effect on tumorigenesis and / or development, and can be used for effective targeted chemotherapeutic treatment.

FIGS. 1A to 1F show the results of measuring the inhibitory activity of VRK1 enzyme activity on the extract of L. trapezae and its fractions prepared according to one embodiment of the present invention.
FIGS. 2A to 2E show the results of measuring the inhibitory activity of VRK1 enzyme and the specific inhibition of BAF of each single active ingredient isolated and identified according to an embodiment of the present invention.
Figures 3a and 3b show the results of evaluating anticancer ability in a tumor animal model.

Hereinafter, the present invention will be described in more detail with reference to preferred embodiments to help understand the present invention. However, the following examples are merely to illustrate the present invention is not limited to the scope of the present invention.

Example  1. Flavor extract and Fraction  Preparation and measurement of enzyme inhibition ability

1.1 Experimental Method

Domestic Baku ( Machilus thunbergii) and filtered through After grinding 20 kg, 80% (v / v) methanol (filter paper was extracted twice at room temperature for 24 hours was added to MeOH) 80L. The resulting filtrate was concentrated under reduced pressure at 45 캜 to obtain a methanol extract.

Depending on the polarity of MeOH magnolia extract obtained again n - hexane (n -hexane), ethyl acetate (EtOAc), and n - butanol was fractionated sequentially (n -BuOH) n - hexane fraction, ethyl acetate fraction, and n - Butanol fraction.

Specifically, 13 fractions were obtained by performing silica gel column chromatography (cc) on n - hexane fraction with increasing polarity of n - hexane - EtOAc mixed solvent. Ethyl acetate fractions were purified by silica gel column chromatography with increasing polarity of CHCl ₃ - acetone mixed solvent to obtain 13 fractions. The n - butanol fraction was further purified by silica gel column chromatography with increasing the polarity of the CHCl ₃ - acetone mixed solvent. Twelve fractions were obtained.

VRK1 (NM_003384) and its substrate BAF (NM_003860) were used for the obtained fractions and in vitro kinase assay (Lopez-Borges S & Lazo PA (2000)) The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumor suppressor protein Oncogene 19 (32): 3656- 3664) was performed to measure the enzyme activity inhibition ability and is shown in Figs. 1A to 1F.

Specifically, 500 ng of the VRK1 protein and 500 ng of the BAF protein were used, respectively, and each fraction was used at the indicated concentration (1 μl of the fraction, unless otherwise indicated). The reaction was carried out at 30 ° C. in a total amount of 20 μl of the reaction mixture (1 μl of the fraction), and the reaction was carried out in the same manner as in Example 1 except that the composition of 20 mM Tris-Cl pH 7.5, 5 mM MgCl 2, 0.5 mM DTT, 150 mM KCl, ³² P- Buffer. After the reaction, all solutions were separated by SDS-PAGE and stained with SYPRO RUBY (Biorad, USA) (Kang TH, et al . (2007) Mitotic histone H3 phosphorylation by vaccinia-related kinase 1 in mammalian cells. Mol Cell Biol 27 (24): 8533-8546)

1.2. result

FIG. 1A is a graph showing how a substance extracted by an organic solvent n -hexane, ethyl acetate (EtOAc), and n -butanol ( n- BuOH) inhibits an enzyme reaction. Inhibition of phosphorylase activity was found to be highest in hexane fraction and BuOH fraction.

1b to 1d show the ability of inhibiting the enzyme activity by further dividing the fraction of each solvent. The fractions 9 to 10 using the hexane solvent having the strongest inhibitory ability were selected to obtain a wider range of fractions (Figs. 1E and 1F). Not only the hexane fraction shows the strongest inhibitory effect on enzyme activity but also the substance dissolved in hexane generally has a high cell permeability. Therefore, the EtOAC fraction and the BuOH fraction are discarded in the following examples and the hexane fraction is continuously analyzed .

Example  2. n- Hexane From fractions  Separation of single active ingredient and measurement of enzyme activity inhibition ability

2.1. Isolation and Identification of Single Active Ingredients

The fraction of n -hexane which showed particularly good inhibitory activity among the fractions measured according to Example 1 was reextracted and purified by column chromatography to narrow the range and obtain a single component fraction.

In detail, except for using 100% (v / v) n -hexane as an extraction solvent instead of methanol, the crude extract was extracted in the same manner as in Example 1 to obtain 151 g of n -hexane extract. Silica gel column chromatography (cc) (Φ 7.5 × 12 cm, n -hexane-EtOAc = 6: 1 → acetone) was performed on 50 g of n- hexane fraction (MTH) Fractions (MTH1 to MTH11) were obtained. 8 fractions (MTH7 + 8-1 to MTH7) were obtained by performing silica gel cc (? 4.5 × 15 cm, CHCl ₃ -acetone = 100: 1) on the fraction MTH7 + 8 [1.7 g, Ve / Vt 0.42-0.57] + 8-11). The small fraction MTH7 + 8-4 (1.3 g, Ve / Vt 0.10-0.35) was purified by ODS cc (Φ 4 × 6 cm, MeOH-H ₂ O = 9: 1 → 10: 1 → 12: 1) (MTH7 + 8-4-1 to MTH7 + 8-4-13), and the fraction having excellent enzyme inhibitory ability was purified to separate three single molecules represented by the following formulas (1), (2) and (3) And the like.

The amount of the isolated single molecule was 136 mg of the compound of Formula 1, 20 mg of the compound of Formula 2, 105 mg of the compound of Formula 3 (0.09% by weight, 0.013% by weight, and 0.07% by weight, respectively, based on the weight of the extract).

The chemical structure of each compound was analyzed by NMR, MS and IR spectral data. The chemical structure of butanolide was ( 3Z, 4S ) -3- (7Z) -7-hexadecen- ( 3Z, 4S ) -3- (7Z) -7-hexadecen-1-ylidenedihydro-4-hydroxy-5-methylene-2 3H) -Furanone) (formula 1), (2E) - methyl ester -2 - [(1S) -1- hydroxy-2-oxopropyl] -2-octadecyl sensan ((2E) -methyl ester-2- (3S , 4S ) -3-hexadecylidenediohydro-4-hydroxy-5-methylene-2 (3S, 1S ) -1-hydroxy-2-oxopropyl] -2-octadecenoic acid ) - furanone (( 3Z, 4S ) -3-hexadecylidenedihydro-4-hydroxy-5-methylene-2 (3H) -Furanone).

[Formula 1]

( 3Z, 4S ) -3- (7Z) -7-hexadecen-1-ylidene dihydro-4-hydroxy-5-methylene-

Molecular formula: C ₂₁ H ₃₄ O ₃

Molecular weight: 334.49

50.0 mg, TLC (ODS F ₂₅₄ ) R _f 0.26, MeOH-H ₂ O = 13: 1

oil. IR (KBr, cm ^-1 ): 3425, 3000, 1780, 1680, 850; EI / MS m / z: 335 [M + H] +, 334 [M] +, 317 [M + HH 2 O] +, 291 [M-43] +, 179, 177, 140, 135, 126, 123 , 109, 97, 95, 83, 81, 79, 70, 69, 67, 57, 55, 43, 41; ^{1 H-NMR (500 MHz,} CDCl 3 ,, δ): 6.69 (1H, td, J = 8.0, 2.0 Hz, H-7), 5.35 (2H, m, H-12), 5.35 (2H, m, H-13), 5.12 (1H , br s, H-3), 4.89 (1H, dd, J = 3.5, 2.0 Hz, H-5b), 4.68 (1H, dd, J = 3.0, 1.0 Hz, H- 5a), 2.78 (2H, m , H-7), 2.03 (2H, m, H-11), 2.03 (2H, m, H-14), 1.50 (2H, q, J = 7.0 Hz, H-8 ), 0.90 (3H, br t, J = 7.0 Hz, H-21); ¹³ C-NMR (500 MHz, CDCl ₃ , 隆): 165.3 (C-1), 157.6 (C-4), 151.2 22.9 (C-12), 27.2 (C-14), 27.0 (C-11), 22.7 (C-20), 14.1 (C-21)

( 2E ) -methyl ester-2 - [( 1S ) -1-hydroxy-2-oxopropyl]

Molecular formula: C ₂₂ H ₄₀ O ₄

Molecular weight: 368.55

Colorless crystals, mp 45.5-46.5 DEG C; IR (KBr, cm ^-1 ): 3500, 3450, 1720, 1700, 1640; EI / MS m / z: 369 [M + H] +, 326 [M + H-Ac] +, 325 [M-Ac] +, 321 [M-74] +, 293 [M-75] +, 140 , 125, 115, 111, 109, 97, 95, 83, 70, 69, 57, 55, 43; ^{1 H-NMR (500 MHz,} CDCl 3 ,, δ): 7.09 (1H, td, J = 7.6 Hz, H-6), 4.92 (1H, br d, H-3), 3.75 (3H, s, OMe ), 2.37 (2H, td, J = 7.5, 7.5 Hz, H-7), 2.17 (3H, s, H-5), 1.54 (2H, q, J = 7.5 Hz, H-8), 0.89 (3H , br t, J = 7.0 Hz, H-23); ^{13 C-NMR (500 MHz,} CDCl 3 ,, δ): 206.3 (C-4), 166.5 (C-1), 149.1 (C-6), 129.8 (C-2), 73.4 (C-3), 21.0 (C-OMe), 31.9 (C-19), 28.7 (C-8), 24.8

(3)

( 3Z, 4S ) -3-hexadecylidenedihydro-4-hydroxy-5-methylene-2 ( 3H )

Molecular formula: C ₂₁ H ₃₆ O ₃

Molecular Weight: 336.51

35.0 mg, TLC (ODS F ₂₅₄ ) R _f 0.19, MeOH-H ₂ O = 15: 1

crystals. IR (KBr, cm ^-1 ): 3425, 1770, 1750, 1660, 850; EI / MS m / z: 337 [M + H] +, 336 [M] +, 319 [M + HH 2 O] +, 293 [M-43] +, 140, 135, 126, 123, 109, 97 , 95, 83, 81, 79, 70, 69, 67, 57, 55, 43, 41; ^{1 H-NMR (500 MHz,} CDCl 3 ,, δ): 6.69 (1H, td, J = 8.0, 2.0 Hz, H-6), 5.12 (1H, br d, H-3), 4.89 (1H, dd , J = 3.0, 2.0 Hz, H-5b), 4.68 (1H, dd, J = 3.0, 1.0 Hz, H-5a), 2.78 (2H, m, H-7), 1.49 (2H, q, J = 7.0 Hz, H-8), 0.89 (3H, br t, J = 7.0 Hz, H-21); ^{13 C-NMR (500 MHz,} CDCl 3 ,, δ): 165.3 (C-1), 157.6 (C-4), 151.3 (C-6), 126.8 (C-2), 90.3 (C-5), 68.9 (C-3), 31.9 (C-19), 28.3 (C-8), 14.1

2.2. Measurement of enzymatic activity inhibition ability

For each single molecule thus obtained, the same method as in Example 1 ( in vitro kinase assay), and the results are shown in Fig. 2a.

As can be seen from the results shown in FIG. 2A, the compound of Chemical Formula 1 showed the most excellent enzyme activity inhibition ability. In order to confirm the effect of inhibiting the enzyme activity according to the concentration by selecting the compound of the formula (1) showing the strongest effect among the compounds of the formulas (1) to (3), enzyme activity inhibition ability was measured in the same manner as described above, And an IC ₅₀ of about 0.8 μM, indicating that VRK1 has excellent ability to inhibit enzyme activity against BAF (FIG. 2B).

On the other hand also indicated the compound with other compounds results, the compounds of formula (II) inhibit the enzyme activity activity comparing the inhibitory capacity enzymes by the concentration of the (general formula 2 and 3) of the formula (I) is very low, IC ₅₀ of the compounds of formula I above As shown in FIG. 2C, the compound of formula (3) was also less effective than the compound of formula (1) but also had enzyme activity inhibitory activity (FIG. 2C)

2.3. VRK1 of BAF Lt; RTI ID = 0.0 > phosphorylation < / RTI >

To investigate whether these inhibitory abilities of VRK1 are enzymatic or substrate specific, enzymes for histone H3 (hH3) (Accession no. BC095447) and casein (Sigma C5890), another substrate of VRK1 The inhibitory activity was measured in the same manner as in Example 1 above.

As shown in FIGS. 2d and 2e, it was confirmed that the compound of Chemical Formula 1 hardly inhibited the activity of the enzyme against histone H3 and casein, unlike the result of the experiment using BAF (FIG. 2b). Therefore, it was found that the compound of formula (I) specifically inhibits BAF phosphorylation by VRK1 rather than inhibition of VRK1 enzyme activity itself.

Example  3. Evaluation of anticancer ability in tumor animal model

3.1. Experimental Method

The formula (I) actually to verify that demonstrate the anti-cancer capacity of 6-week-old c57BL / 6 female mice B16F10 cells (1.0 x 10 ⁵⁾ of the same kind originating from the (each experiment by 3 rats) in a tumor model compounds of (Korea Cell Line Bank - cat no. 80008) were subcutaneously injected to develop melanoma. Then, 100 μl of the compound of formula (1) (10 mg / kg, 20 mg / kg, 40 mg / kg) was directly injected three times at intervals of one week, Figure 3b (weight of tumor measured by extraction of tumor in treated group by concentration) (g)) (Choi BH et al., Cancer Lett. 2008 Mar 8 ; 261 (1): 37-45. Epub 2007 Dec 26.)

3.2. result

As shown in Figs. 3A and 3B, in the experimental group treated with the compound of the formula (1) compared with the control group in which only the solvent (containing 10% (w / v) DMSO in PBS) was used without any treatment, And the size was significantly decreased. In addition, the tumor reduction effect was dependent on the treatment concentration of the compound. In particular, in the experimental group treated with 40 mg / kg, the weight of the tumor in the control group was about 0.55 g, The tumor weight was reduced by about 1/11 times as compared to the control group.

Thus, the compound of formula (1) has excellent anticancer ability and can be effectively used as an anticancer composition.

Claims (7)

Anti-cancer composition comprising at least one selected from the group consisting of hul-bak extract, the compound isolated from the hoo-bak extract, and derivatives of the compound as an active ingredient
The method of claim 1,
The anti-cancer composition, the compound isolated from the extract, or the derivative of the compound, anticancer composition that inhibits the formation or development of cancer through the inhibition of phosphorylation of BAF, a substrate of VRK1
The method of claim 1,
The thick gourd extract is an anticancer composition comprising a thick gourd extracted with one or more organic solvents selected from the group consisting of n -hexane, ethyl acetate, n -butanol, and methanol.
The method of claim 3,
The thick extract is at least one fraction selected from the group consisting of n -hexane fraction, ethyl acetate fraction, and n -butanol fraction obtained by sequentially fractionating the organic solvent extract with n -hexane, ethyl acetate, and n -butanol. Anticancer composition
The method of claim 1,
The compound or a derivative of the compound is an anticancer composition represented by the following formula (4)
[Chemical Formula 4]

In Chemical Formula 4,
R ₁ is hydrogen and R ₂ is a C ₁₃ to C ₁₇ straight chain hydrocarbon group which is saturated or unsaturated by one or five double bonds.
The method of claim 5,
The compound is an anticancer composition which is a compound of Formula 1 or 3
[Formula 1]

(3)

The method of claim 1,
The anticancer composition is for anticancer comprising at least one member selected from the group consisting of the hupak extract, the compound separated from the huhu extract, and derivatives of the compound in an amount of 0.0001 ~ 99.9% by weight based on the total weight of the composition Composition.

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