CANCER CELL PROLIFERATION SUPPRESSION AGENT AND COMPOSITION FOR SUPPRESSING PROLIFERATION OF CANCER CELLS

Abstract

A cancer cell proliferation suppression agent containing, as an active ingredient, an inositol derivative in which a sugar is bound to inositol is provided. Furthermore, a composition for suppressing proliferation of cancer cells containing the above-mentioned cancer cell proliferation suppression agent and a pharmaceutically acceptable carrier is provided.

Claims

1. A cancer cell proliferation suppression agent comprising, as an active ingredient, an inositol derivative in which a sugar is bound to inositol.

2. The cancer cell proliferation suppression agent according to claim 1, wherein the sugar is glucose or an oligosaccharide containing glucose as a constitutional unit.

3. The cancer cell proliferation suppression agent according to claim 1, wherein the inositol is myo-inositol.

4. The cancer cell proliferation suppression agent according to claim 1, wherein the cancer cell proliferation suppression agent suppresses expression of a CYP1A1 gene and a CYP1B1 gene.

5. The cancer cell proliferation suppression agent according to claim 1, wherein the cancer cell proliferation suppression agent suppresses expression of an ARNT gene.

6. The cancer cell proliferation suppression agent according to claim 1, wherein the cancer cell proliferation suppression agent suppresses production of active oxygen.

7. A composition for suppressing proliferation of cancer cells comprising: the cancer cell proliferation suppression agent according to claim 1; and a pharmaceutically acceptable carrier.

8. The composition for suppressing proliferation of cancer cells according to claim 7, wherein a total content of the inositol derivative is 0.1% to 2% by mass.

9. The composition for suppressing proliferation of cancer cells according to claim 7, further comprising a tocopherol phosphate ester or a salt thereof.

10. The composition for suppressing proliferation of cancer cells according to claim 9, wherein the tocopherol phosphate ester is an α-tocopherol phosphate ester.

11. The composition for suppressing proliferation of cancer cells according to claim 9, wherein the salt of the tocopherol phosphate ester is a sodium salt of the tocopherol phosphate ester.

12. The composition for suppressing proliferation of cancer cells according to claim 9, wherein a total content of the tocopherol phosphate ester or the salt thereof is 0.1% to 2% by mass.

13. The cancer cell proliferation suppression agent according to claim 3, wherein the cancer cell proliferation suppression agent suppresses expression of a CYP1A1 gene and a CYP1B1 gene.

14. The cancer cell proliferation suppression agent according to claim 3, wherein the cancer cell proliferation suppression agent suppresses expression of an ARNT gene.

15. The cancer cell proliferation suppression agent according to claim 3, wherein the cancer cell proliferation suppression agent suppresses production of active oxygen.

16. A composition for suppressing proliferation of cancer cells comprising: the cancer cell proliferation suppression agent according to claim 3; and a pharmaceutically acceptable carrier.

17. The composition for suppressing proliferation of cancer cells according to claim 16, wherein a total content of the inositol derivative is 0.1% to 2% by mass.

18. The composition for suppressing proliferation of cancer cells according to claim 16, further comprising a tocopherol phosphate ester or a salt thereof.

19. The composition for suppressing proliferation of cancer cells according to claim 18, wherein the tocopherol phosphate ester is an α-tocopherol phosphate ester.

20. The composition for suppressing proliferation of cancer cells according to claim 18, wherein the salt of the tocopherol phosphate ester is a sodium salt of the tocopherol phosphate ester.

21. The composition for suppressing proliferation of cancer cells according to claim 18, wherein a total content of the tocopherol phosphate ester or the salt thereof is 0.1% to 2% by mass.

Description

EXAMPLES

[0156] Hereinafter, the present invention will be described with reference to examples, but the present invention is not limited to the following examples.

Manufacturing Example of Inositol Derivative

[0157] Myo-inositol and β-cyclodextrin were reacted in the presence of cyclodextrin glucanotransferase to produce an inositol derivative in which glucose or an oligosaccharide having glucose as a monosaccharide unit was bound to myo-inositol. As a result of analyzing the produced inositol derivative by liquid chromatography—mass spectrometry (LC-MS), the proportion of molecules in which the number of glucose of a glucose chain bound to myo-inositol was one was 12% by mass, the proportion of molecules in which the number thereof was two was 30% by mass, the proportion of molecules in which the number thereof was three was 9% by mass, the proportion of molecules in which the number thereof was four was 12% by mass, and the proportion of molecules in which the number thereof was five was 2% by mass.

[0158] In the following experimental examples, the inositol derivative manufactured in the present manufacturing example was used.

Experimental Example 1

[0159] (Effect of Suppressing Expression of CYP1A1 Gene and CYP1B1 Gene)

[0160] The effect of the inositol derivative on suppressing the expression of a CYP1A1 gene and a CYP1B1 gene in normal human epidermal keratinocytes (NHEK, manufactured by KURABO INDUSTRIES LTD.) was measured under the following conditions.

[0161] The NHEK cells were seeded in a HuMedia KG2 medium manufactured by KURABO INDUSTRIES LTD. at the seeding density of 10000 cells/cm.sup.2, and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, an aqueous solution of the inositol derivative or an aqueous solution of myo-inositol was added to the culture medium so that the final concentration of the inositol derivative or myo-inositol was 0.001% by mass, or water (pure water) was added to the culture medium, and culturing was further performed for 24 hours. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 48 hours. Thereafter, the NHEK cells were recovered to extract total RNA using Nucleospin™ RX (Takara Bio Inc.). From the obtained RNAs, cDNA was synthesized using a PrimeScript (registered trademark) RT Master Mix (Takara Bio Inc.). Using this cDNA as a template, the expression levels of the CYP1A1 gene and the CYP1B1 gene were quantitatively determined by quantitative real-time PCR using primers (QuantiTect Primer Assays, manufactured by QIAGEN) specific to the CYP1A1 gene and the CYP1B1 gene. As an internal standard gene, the expression level of a GAPDH gene, which is a housekeeping gene in which expression fluctuation due to the addition of atmospheric dust is not shown, was quantitatively determined (primer used: Perfect Real Time Primer, manufactured by Takara Bio Inc.), and the expression levels of the CYP1A1 gene and the CYP1B1 gene were standardized based on the expression level of GAPDH. One to which atmospheric dust was not added was used as a control.

[0162] Table 1 shows the results. Table 1 shows the expression level of each gene in the atmospheric dust-added group as a relative expression level when the expression level of each gene in the control to which atmospheric dust was not added was 1. In the inositol derivative-added group, the expression levels of both the CYP1A1 gene and the CYP1B1 gene were reduced as compared to the water-added group and the myo-inositol-added group. From these results, it was confirmed that the inositol derivative has a high suppression effect on the expression of the CYP1A1 gene and the CYP1B1 gene induced by atmospheric dust.

TABLE-US-00001 TABLE 1 Relative gene expression level Sample CYP1A1 CYP1B1 Atmospheric dust Water 1.00 1.00 not added Atmospheric dust Water 4.11 4.30 added Inositol derivative 0.57 0.41 myo-Inositol 3.10 1.08

Experimental Example 2

[0163] (Effect of Suppressing Expression of ARNT Gene)

[0164] The effect of the inositol derivative on suppressing the expression of an ARNT gene in normal human epidermal keratinocytes (NHEK, manufactured by KURABO INDUSTRIES LTD.) was measured under the following conditions.

[0165] The NHEK cells were seeded in a HuMedia KG2 medium manufactured by KURABO INDUSTRIES LTD. at the seeding density of 10000 cells/cm.sup.2, and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, an aqueous solution of the inositol derivative or an aqueous solution of myo-inositol was added to the culture medium so that the final concentration of the inositol derivative or myo-inositol was 0.001% by mass, or water (pure water) was added to the culture medium, and culturing was further performed for 24 hours. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 48 hours. Thereafter, the NHEK cells were recovered to extract total RNA using Nucleospin™ RX (Takara Bio Inc.). From the obtained RNAs, cDNA was synthesized using a PrimeScript (registered trademark) RT Master Mix (Takara Bio Inc.). Using this cDNA as a template, the expression level of the ARNT gene was quantitatively determined by quantitative real-time PCR using a primer specific to the ARNT gene (Perfect Real Time Primer, manufactured by Takara Bio Inc.). As an internal standard gene, the expression level of GAPDH was quantitatively determined (primer used: Perfect Real Time Primer, manufactured by Takara Bio Inc.), and the expression level of the ARNT gene was standardized based on the expression level of GAPDH. One to which atmospheric dust was not added was used as a control.

[0166] Table 2 shows the results. Table 2 shows the expression level of the ARNT gene in the atmospheric dust-added group as a relative expression level when the expression level of the ARNT gene in the control to which atmospheric dust was not added was 1. In the inositol derivative-added group, the expression level of the ARNT gene was reduced as compared to the water-added group and the myo-inositol-added group. From these results, it was confirmed that the inositol derivative has a high suppression effect on the expression of the ARNT gene induced by atmospheric dust.

TABLE-US-00002 TABLE 2 Relative gene expression level Sample ARNT Atmospheric dust Water 1.00 not added Atmospheric dust Water 1.74 added Inositol derivative 0.36 myo-Inositol 1.85

Experimental Example 3

[0167] (Effect (1) of Suppressing ROS Production)

[0168] The effect of the inositol derivative on suppressing ROS production in normal human epidermal keratinocytes (NHEK, manufactured by KURABO INDUSTRIES LTD.) was measured under the following conditions.

[0169] The NHEK cells were seeded in a HuMedia KG2 medium manufactured by KURABO INDUSTRIES LTD. at the seeding density of 10000 cells/cm.sup.2, and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, an aqueous solution of the inositol derivative or an aqueous solution of myo-inositol was added to the culture medium so that the final concentration of the inositol derivative or myo-inositol was 0.001% by mass, or water (pure water) was added to the culture medium, and culturing was further performed for 24 hours. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 48 hours in the same conditions as above. Thereafter, the ROS production amount was measured using a ROS assay kit (manufactured by OZ BIOSCIENCES). After washing the cells from which the culture medium was removed with a phosphate buffer solution (PBS, manufactured by FUJIFILM Wako Pure Chemical Corporation), 100 μL of dichlorofluorescein diacetate attached to the ROS assay kit was added to each group of the cells, and the cells were left to stand at 37° C. for 30 minutes while being shielded from light. After washing the cells with PBS again, 100 μL of PBS was added, and the fluorescence intensity at an excitation wavelength of 485 nm/an absorption wavelength of 535 nm was measured with a microplate reader i-Control (manufactured by Tecan Group Ltd.). One to which atmospheric dust was not added was used as a control.

[0170] Table 3 shows the results. Table 3 shows the ROS production amount in the atmospheric dust-added group as a relative amount when the fluorescence intensity in the control to which atmospheric dust was not added was 1. In the inositol derivative-added group, the ROS production amount was reduced as compared to the water-added group and the myo-inositol-added group. From these results, it was confirmed that the inositol derivative has a high suppression effect on the ROS production induced by atmospheric dust. On the other hand, in the myo-inositol-added group, the effect of suppressing ROS production was not recognized as compared to the water-added group.

TABLE-US-00003 TABLE 3 Relative ROS Sample production amount Atmospheric dust Water 1.00 not added Atmospheric dust Water 1.46 added Inositol derivative 1.19 myo-Inositol 1.83

Experimental Example 4

[0171] (Effect (1) of Suppressing Proliferation of Cancer Cells)

[0172] The effect of the inositol derivative on suppressing the proliferation of cancer cells in a cell line derived from Lewis lung carcinoma (LLC, JCRB Cell Bank) was measured under the following conditions.

[0173] The LLC cells were seeded at the seeding density of 50000 cells/cm.sup.2 in a culture medium in which a Ham F 10 medium and an L15 medium (both manufactured by Sigma-Aldrich) were mixed at the ratio of 3:7 (volume ratio), and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, an aqueous solution of the inositol derivative or an aqueous solution of myo-inositol was added to the culture medium so that the final concentration of the inositol derivative or myo-inositol was 0.001% by mass, or water (pure water) was added to the culture medium, and culturing was further performed for 24 hours. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 48 hours in the same conditions as above. Thereafter, the culture medium was replaced with a medium containing 10% (V/V) of WST-8 of Nacalai Tesque Inc., and after further culturing for 3 hours, the absorbance at the wavelength of 450 nm was measured with a microplate reader i-Control (manufactured by Tecan Group Ltd.). One to which atmospheric dust was not added was used as a control.

[0174] Table 4 shows the results. Table 4 shows the cell proliferation amount in the atmospheric dust-added group as a relative amount when the absorbance in the control to which atmospheric dust was not added was 1. In the inositol derivative-added group, the cell proliferation amount of cancer cells was reduced as compared to the water-added group and the myo-inositol-added group. From these results, it was confirmed that the inositol derivative has a high suppression effect on the cell proliferation of cancer cells accelerating due to atmospheric dust.

TABLE-US-00004 TABLE 4 Relative cell proliferation amount Atmospheric dust Water 1.00 not added Atmospheric dust Water 2.31 added Inositol derivative 1.13 myo-Inositol 2.03

Experimental Example 5

[0175] (Effect of Suppressing Invasion of Cancer Cells)

[0176] The effect of the inositol derivative on suppressing the invasion of cancer in a cell line derived from Lewis lung carcinoma (LLC, JCRB Cell Bank) was measured under the following conditions. A CytoSelect invasion assay kit manufactured by Cell Biolabs, Inc. was used for a test.

[0177] The LLC cells were seeded in a chamber plate for invasion tests attached to the above-mentioned invasion assay kit so that the concentration was 100000 cells/mL using a culture medium in which a Ham F10 medium and an L15 medium (both manufactured by Sigma-Aldrich) were mixed at the ratio of 3:7 (volume ratio), and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, an aqueous solution of the inositol derivative or an aqueous solution of myo-inositol was added to the culture medium so that the final concentration of the inositol derivative or myo-inositol was 0.001% by mass, or water (pure water) was added to the culture medium, and culturing was further performed for 24 hours. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 6 hours. Next, the medium containing atmospheric dust was removed and replaced with a new medium, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 18 hours. Thereafter, the cells were stained using the above-mentioned invasion assay kit, and the fluorescence intensity at an excitation wavelength of 480 nm/an absorption wavelength of 570 nm was measured with a microplate reader i-Control (manufactured by Tecan Group Ltd.). One to which atmospheric dust was not added was used as a control.

[0178] Table 5 shows the results. Table 5 shows the cell invasion in the atmospheric dust-added group as a relative amount when the fluorescence intensity in the control to which atmospheric dust was not added was 1. In the inositol derivative-added group, the cell invasion of cancer cells was reduced as compared to the water-added group and the myo-inositol-added group. From these results, it was confirmed that the inositol derivative suppresses the cell invasion of cancer cells accelerating due to atmospheric dust.

TABLE-US-00005 TABLE 5 Relative cell invasion Atmospheric dust Water 1.00 not added Atmospheric dust Water 1.67 added Inositol derivative 1.23 myo-Inositol 1.53

Experimental Example 6

[0179] (Effect (2) of Suppressing ROS Production)

[0180] The effect of the inositol derivative and Na tocopherol phosphate on suppressing ROS production in normal human epidermal keratinocytes (NHEK, manufactured by KURABO INDUSTRIES LTD.) was measured under the following conditions. As the following Na tocopherol phosphate, TPNa (registered trademark) (manufactured by Showa Denko K. K.), which is sodium d1-α-tocopheryl phosphate, was used.

[0181] The NHEK cells were seeded in a HuMedia KG2 medium manufactured by KURABO INDUSTRIES LTD. at the seeding density of 10000 cells/cm.sup.2, and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, Na tocopherol phosphate alone (final concentration of 10 μM in the culture medium), the inositol derivative alone (final concentration of 0.001% by mass in the culture medium), or a combination of Na tocopherol phosphate (final concentration of 10 μM in the culture medium) and the inositol derivative (final concentration of 0.001% by mass in the culture medium) was added to the culture medium. The Na tocopherol phosphate and the inositol derivative were dissolved in an aqueous solution of 0.05% (V/V) ethanol and added to the culture medium so that the final concentrations were as described above. Furthermore, one in which an aqueous solution of 0.05% (V/V) ethanol was added to the culture medium was also prepared. Thereafter, culturing was performed for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 48 hours. Thereafter, the ROS production amount was measured using a ROS assay kit (manufactured by OZ BIOSCIENCES). After washing the cells from which the culture medium was removed with a phosphate buffer solution (PBS, manufactured by FUJIFILM Wako Pure Chemical Corporation), 100 μL of dichlorofluorescein diacetate attached to the ROS assay kit was added to each group of the cells, and the cells were left to stand at 37° C. for 30 minutes while being shielded from light. After washing the cells with PBS again, 100 μL of PBS was added, and the fluorescence intensity at an excitation wavelength of 485 nm/an absorption wavelength of 535 nm was measured with a microplate reader i-Control (manufactured by Tecan Group Ltd.). One to which atmospheric dust was not added was used as a control.

[0182] Table 6 shows the results. Table 6 shows the ROS production amount in the atmospheric dust-added group as a relative amount when the fluorescence intensity in the control to which atmospheric dust was not added was 1. In any of the group in which the inositol derivative was added alone, the group in which the Na tocopherol phosphate was added alone, and the inositol derivative+Na tocopherol phosphate-added group, the ROS production amount was reduced as compared to the 0.05% ethanol-added group. In the inositol derivative+Na tocopherol phosphate-added group, the production of ROS was reduced than the group in which the inositol derivative was added alone and the group in which the Na tocopherol phosphate was added alone. From these results, it was confirmed that a synergistic suppression effect of the inositol derivative on ROS production induced by atmospheric dust is obtained when the inositol derivative is used together with Na tocopherol phosphate.

TABLE-US-00006 TABLE 6 Relative ROS Sample production amount Atmospheric dust 0.05% Ethanol 1.00 not added Atmospheric dust 0.05% Ethanol 2.41 added Na tocopherol phosphate 1.53 Inositol derivative 1.73 Na tocopherol phosphate + 1.04 inositol derivative

Experimental Example 7

[0183] (Effect (2) of Suppressing Proliferation of Cancer Cells)

[0184] The effect of the inositol derivative and Na tocopherol phosphate on suppressing the proliferation of cancer cells in a cell line derived from Lewis lung carcinoma (LLC, JCRB Cell Bank) was measured under the following conditions. As the following Na tocopherol phosphate, TPNa (registered trademark) (manufactured by Showa Denko K. K.), which is sodium d1-α-tocopheryl phosphate, was used.

[0185] The LLC cells were seeded at the seeding density of 50000 cells/cm.sup.2 in a culture medium in which a Ham F10 medium and an L15 medium (both manufactured by Sigma-Aldrich) were mixed at the ratio of 3:7 (volume ratio), and cultured for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Next, Na tocopherol phosphate alone (final concentration of 10 μM in the culture medium), the inositol derivative alone (final concentration of 0.001% by mass in the culture medium), or a combination of Na tocopherol phosphate (final concentration of 10 μM in the culture medium) and the inositol derivative (final concentration of 0.001% by mass in the culture medium) was added to the culture medium. The Na tocopherol phosphate and the inositol derivative were dissolved in an aqueous solution of 0.05% (V/V) ethanol and added to the culture medium so that the final concentrations were as described above. Furthermore, one in which an aqueous solution of 0.05% (V/V) ethanol was added to the culture medium was also prepared. Thereafter, culturing was performed for 24 hours under the conditions of 37° C. and 5% CO.sub.2. Thereafter, 0.1 mL of a DMSO solution of atmospheric dust (NIST 1648a) was added per 100 mL of the culture medium so that the final concentration of the atmospheric dust in the culture medium was 500 μg/mL, and culturing was further performed for 48 hours. Thereafter, the culture medium was replaced with a medium containing 10% (V/V) of WST-8 of Nacalai Tesque Inc., and after further culturing for 3 hours, the absorbance at the wavelength of 450 nm was measured with a microplate reader i-Control (manufactured by Tecan Group Ltd.). One to which atmospheric dust was not added was used as a control.

[0186] Table 7 shows the results. Table 7 shows the cell proliferation amount in the atmospheric dust-added group as a relative amount when the absorbance in the control to which atmospheric dust was not added was 1. In any of the group in which the inositol derivative was added alone, the group in which the Na tocopherol phosphate was added alone, and the inositol derivative+Na tocopherol phosphate-added group, the cell proliferation amount was reduced as compared to the 0.05% ethanol-added group. In the inositol derivative+Na tocopherol phosphate-added group, the cell proliferation amount was reduced than the group in which the inositol derivative was added alone and the group in which the Na tocopherol phosphate was added alone. From these results, it was confirmed that the inositol derivative synergistically suppresses the cell proliferation of cancer cells accelerating due to atmospheric dust by using the inositol derivative together with Na tocopherol phosphate.

TABLE-US-00007 TABLE 7 Relative cell Sample proliferation amount Atmospheric dust 0.05% Ethanol 1.00 not added Atmospheric dust 0.05% Ethanol 1.69 added Na tocopherol phosphate 1.33 Inositol derivative 1.42 Na tocopherol phosphate + 0.94 inositol derivative

Prescription Examples

[0187] Prescription examples of the composition for suppressing proliferation of cancer cells are described below. As an inositol derivative in the following prescription examples, the inositol derivative manufactured in [Manufacturing example of inositol derivative] is the exemplary example. Furthermore, as the following Na tocopherol phosphate, TPNa (registered trademark) (manufactured by Showa Denko K. K.), which is sodium d1-α-tocopheryl phosphate, is the exemplary example.

Prescription Example 1

[0188] Table 8 shows prescription examples of a spreading agent (spray).

TABLE-US-00008 TABLE 8 Prescription (mass %) Prescription Prescription Component Example 1-1 Example 1-2 Inositol derivative 0.5 0.5 Na tocopherol phosphate — 0.2 Carboxy vinyl polymer 1 1 Ethyl alcohol 30 30 Phenoxyethanol 0.2 0.2 Water 68.3 68.1

[0189] (Prescription Example 2) Table 9 shows prescription examples of a spreading agent (aerosol).

TABLE-US-00009 TABLE 9 Prescription (mass %) Prescription Prescription Component Example 2-1 Example 2-2 Inositol derivative 1 0.5 Na tocopherol phosphate — 0.2 Ethyl alcohol 35 35 Water 10 10 Nitrogen gas (propellant) 54 54.3

Prescription Example 3

[0190] Table 10 shows prescription examples of a spreading agent (spray for skin).

TABLE-US-00010 TABLE 10 Prescription (mass %) Prescription Prescription Component Example 3-1 Example 3-2 Inositol derivative 1 0.5 Na tocopherol phosphate — 0.2 Carboxy vinyl polymer 1 1 Ethyl alcohol 25 25 Titanium oxide 0.5 0.5 Sodium hyaluronate 0.5 0.5 Phenoxyethanol 0.2 0.2 Water 71.8 72.1

Prescription Example 4

[0191] Table 11 shows prescription examples of a nasal drop.

TABLE-US-00011 TABLE 11 Prescription (mass %) Prescription Prescription Component Example 4-1 Example 4-2 Inositol derivative 0.5 0.5 Na tocopherol phosphate — 0.2 Carboxy vinyl polymer 0.5 0.5 Sodium chloride 1   1 Benzalkonium chloride 0.2 0.2 Ethanol 0.1 0.1 Edetic acid 0.2 0.2 Menthol Minute amounts Minute amounts Sorbitan sesquioleate 0.2 0.2 Water 96.8  96.6

INDUSTRIAL APPLICABILITY

[0192] According to the present invention, a cancer cell proliferation suppression agent which can suppress proliferation of cancer cells accelerating due to atmospheric pollutants, and a composition for suppressing proliferation of cancer cells containing the above-mentioned cancer cell proliferation suppression agent are provided.