Antitumor agent, pharmaceutical composition, and antitumor composition

Antitumor agents derived from Magnolia sieboldii extracts, particularly Magnolia nigricans essential oil, address safety concerns of citral by providing a potent and safe antitumor effect through inhalation, suitable for various applications.

JP2026007464APending Publication Date: 2026-01-16TOHO UNIV FOUND
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Patent Information

Application Number
JP2024107325
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2024-07-03
Publication Date
2026-01-16

AI Technical Summary

Technical Problem

Existing antitumor agents containing citral, a known fragrance component, pose safety concerns due to cytotoxicity and potential allergic reactions, while Magnolia nigricans, despite its traditional use, lacks thorough medical efficacy research.

Method used

Development of antitumor agents using Magnolia sieboldii extracts, particularly Magnolia nigricans essential oil, which includes citral or 1,8-cineole, offering a high antitumor effect with reduced toxicity and broader applications.

Benefits of technology

The antitumor agents provide a strong antitumor effect in small amounts, are safe for human use, and have versatile applications, including inhalation through air fresheners and medical supplies, without causing skin irritation.

✦ Generated by Eureka AI based on patent content.

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Abstract

To provide an antitumor agent, a pharmaceutical composition and a composition for antitumor having high antitumor action with a small amount, high safety to the human body and a wide application range to a composition having a fragrance component.SOLUTION: There are provided an anti-tumor agent containing an odorous Magnolia Kobus extract component, the anti-tumor agent containing citral or 1, 8-cineole, the anti-tumor agent in which the odorous Magnolia Kobus extract component is an odorous Magnolia Kobus essential oil or an extract thereof, the anti-tumor agent for treating breast, colon, pancreatic, esophageal or gastric cancers, and a pharmaceutical composition and an anti-tumor composition containing the same.SELECTED DRAWING: None
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Description

[Technical Field]

[0001] The present invention relates to an antitumor agent, a pharmaceutical composition and an antitumor composition used in the treatment, such as the prevention or treatment of various cancers. [Background technology]

[0002] Some plants whose components have traditionally been used as fragrances or spices have been found to have medicinal effects, and their uses are currently being studied.

[0003] Patent Document 1 describes a method for preventing or treating solid and soft tissue tumors and proliferative diseases in a subject in need thereof, comprising administering to the subject an effective amount of a component derived from a plant species or genus selected from the group consisting of plant parts, extracts, fractions, active ingredients, synthetic analogs, mimetics, or combinations thereof, and the component treats solid and soft tissue tumors and proliferative diseases. Examples of such plant species include Nigella sativa (sweet nigella) and Thymus Capitatus (Persian hyssop). Some of these plant species contain citral as an ingredient. This technology aims to use the components of the above plants, which have traditionally been used as fragrances, for the prevention or treatment of cancer, tumors, and the like.

[0004] On the other hand, Magnolia nigricans (Magnolia Salicifolia) is a tree native to Japan that belongs to the Magnoliaceae family and its essential oil is popular for its sweet, refreshing scent. Magnolia nigricans is harvested in small quantities, making its essential oil valuable. Magnolia nigricans' dried flower buds, known as shin'i, are used as a herbal medicine to treat headaches and rhinitis. The fragrance is also known to have a relaxing effect. Based on these examples of traditional use, its safety to the human body is well known. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Special Publication No. 2023-522299 Summary of the Invention [Problem to be solved by the invention]

[0006] The technology of Patent Document 1 involves plants containing citral, a known fragrance component. Citral is already known to have medical effects such as anti-inflammatory properties, but citral is also known to be cytotoxic, and as an organic compound, it can be irritating and may cause allergic reactions on the skin, so there are safety concerns when used alone on the human body.

[0007] On the other hand, although Magnolia nigricans has traditionally been used for its fragrance, including the components that come into contact with the human body, due to the small amount that can be harvested, little research has been done into the medical effects and efficacy of its components.

[0008] The present invention has been made in consideration of the above-mentioned circumstances, and its object is to provide an antitumor agent, a pharmaceutical composition, and an antitumor composition that have a high antitumor effect in a small amount, are highly safe for the human body, and have a wide range of applications compared to compositions containing fragrance components. [Means for solving the problem]

[0009] In order to solve the above problems, the present invention has the following aspects. [1] An antitumor agent containing extracts of Magnolia sieboldii. [2] The antitumor agent according to [1], which contains citral or 1,8-cineole. [3] The antitumor agent according to [1] or [2], wherein the extract component of Magnolia nigricans is Magnolia nigricans essential oil or an extract thereof. [4] The antitumor agent according to any one of [1] to [3], which is for treating breast cancer, colon cancer, pancreatic cancer, esophageal cancer, or gastric cancer. [5] A pharmaceutical composition comprising an antitumor agent according to any one of [1] to [4]. [6] An antitumor composition comprising the antitumor agent according to any one of [1] to [4], for inclusion in an air freshener or deodorant. [7] An antitumor composition comprising the antitumor agent according to any one of [1] to [4], for inclusion in medical supplies, food, cosmetic products or decorative products. [8] An antitumor composition comprising an antitumor agent described in any one of [1] to [4], or an antitumor agent composition described in any one of [5] to [7], which is intended to be sprayed or evaporated into the air and inhaled by the human body. [9] An antitumor composition comprising an antitumor agent described in any one of [1] to [4], or an antitumor agent composition described in any one of [5] to [7], which is used by spraying or evaporating so as to contain 1.0 pL / ml or more of citral in the air. [Effects of the Invention]

[0010] According to the present invention, it is possible to provide an antitumor agent, a pharmaceutical composition, and an antitumor composition that have a high antitumor effect even in a small amount, are highly safe for the human body, and have a wide range of applications compared to compositions containing fragrance components. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 is a photograph showing the results of an MTT assay in this example that verified the effect of Magnolia sieboldii essential oil on mouse breast cancer cells. [Figure 2] FIG. 1 is a graph showing an analysis of the relationship between distance from essential oil and cancer cell survival rate in this example. [Figure 3] This is a photograph showing the results of an MTT assay in this example, which examined the effects of various concentrations of Magnolia sieboldii essential oil on mouse breast cancer cells. [Figure 4] FIG. 1 is a graph showing the quantification results of the tumor growth inhibitory effect of Magnolia miltiorrhiza essential oil in this example. [Figure 5]This is a photograph of fluorescent staining showing the cell death induction effect of 4T1 cells reacted with the evaporated components of Magnolia sieboldii essential oil in this example. [Figure 6] FIG. 1 shows the body weights of mice in both the MS (inhaled Magnolia kobushi essential oil components) and control groups in this example. [Figure 7] FIG. 1 shows the tumors excised from the mice of both groups in this example. [Figure 8] FIG. 1 is a photograph showing the results of an MTT assay for the antitumor effects of citral and 1,8-cineole in this example. [Figure 9] FIG. 1 is a graph showing IC50 quantification for the antitumor effects of citral and 1,8-cineole in this example. [Figure 10] FIG. 1 is a photograph of a Western blot showing the effect of citral on each protein in breast cancer cells in this example. [Figure 11] FIG. 1 is a graph showing the cell viability of each type of cell in the presence of an antitumor agent in this example. DETAILED DESCRIPTION OF THE INVENTION

[0012] The antitumor agent, pharmaceutical composition, and antitumor composition according to the present invention will be described below with reference to embodiments, although the present invention is not limited to the following embodiments.

[0013] (Antineoplastic agent) The antitumor agent of this embodiment contains an extract component from Magnolia sieboldii. Antitumor agents broadly refer to compounds that act to reduce tumors, such as tumor cells and tumor tissues. For example, they refer to compounds that, when administered to tumor cells, have the effect of causing cell death or inhibiting proliferation. Tumors include various cancer cells and cancer tissues. The purpose of use of an antitumor agent broadly refers to uses related to the treatment of tumor-related diseases, such as the treatment, prevention, and prevention of recurrence of cancer.

[0014] The antitumor agent can be widely used to treat various tumors, such as cancers in various organs, including breast cancer, colon cancer, pancreatic cancer, esophageal cancer, and gastric cancer. The antitumor agent is particularly preferably used for treating breast cancer. The inventors have found that the antitumor agent of this embodiment is particularly effective against breast cancer cells and breast cancer.

[0015] Magnolia serrata extract refers broadly to ingredients extracted from the Magnolia serrata (Magnolia Salicifolia) plant. The plant includes the tree (branches, trunks), leaves, seeds, fruits, flowers, and roots. The ingredients can be widely used regardless of the method used to extract them.

[0016] The Magnolia nigra extract component is preferably Magnolia nigra essential oil or an extract thereof. Here, essential oil broadly refers to an extract from the flowers, leaves, peel, fruit, heartwood, roots, seeds, bark, resin, etc. of a plant. Essential oil is known as an extract containing active ingredients from a plant at a high concentration. The Magnolia nigra extract component of this embodiment is more preferably extracted from Magnolia nigra branches. The essential oil can be extracted by a conventionally known method, for example, steam distillation. Magnolia nigra essential oil has been widely used as an extract of Magnolia nigra components and is easy to produce. Furthermore, the present inventors have found that Magnolia nigra essential oil, especially that extracted from Magnolia nigra branches, has a particularly strong antitumor effect. The components of Magnolia occidentalis essential oil vary depending on the material (the Magnolia occidentalis tree used), but it is preferable to use an antitumor agent of this embodiment that contains citral or 1,8-cineole, as described below.

[0017] The antitumor agent of this embodiment preferably contains citral or 1,8-cineole. Citral (3,7-dimethyl-2,6-octadienal, C 10 H16 O) is also called lemonal, and is contained in various plants, such as lemongrass and citrus fruits, which have strong fragrances, and is widely known as the odor component of these so-called citrus fruits. Citral includes geranial (E-form) and neral (Z-form), which are cis-trans isomers, and the citral in this embodiment may be either of these.

[0018] It has been known that citral has antitumor effects. In addition, the present inventors have confirmed in vitro experiments that citral has antitumor effects through mitochondrial apoptosis reactions. However, the compound citral itself is cytotoxic and is not sufficiently safe for the human body. The present inventors have clarified that the Magnolia maggiore extract of this embodiment contains a large amount of citral and has low toxicity. It is presumed that the Magnolia maggiore extract has an antitumor effect due to the citral and is highly safe due to the other components contained in the Magnolia maggiore extract.

[0019] The antitumor agent of this embodiment also preferably contains 1,8-cineole. 1,8-cineole (also known as 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octane, eucalyptol, etc.) is a component known to be contained in plants of the genus Eucalyptus, such as mugwort, bay leaf, basil, and sage. It is particularly known to be extractable from eucalyptus essential oil. 1,8-cineole is used for its aroma, and is also known to have anti-inflammatory effects as a medicinal effect. On the other hand, it is known that the compound 1,8-cineole alone is irritating to mucous membranes and skin, and is not sufficiently safe for the human body. The present inventors have revealed that the Magnolia sieboldii extract component of this embodiment contains a large amount of 1,8-cineole and has low toxicity.

[0020] (Method of use of antitumor agents) The antitumor agent of this embodiment can be widely used for the purpose of antitumor cells and antitumor tissues. Specific examples include use in various treatments for the various cancers mentioned above. The method of using the antitumor agent of this embodiment may be, for example, a trial use method or a medically effective treatment method. The medically effective treatment method may be, for example, a medical treatment method or a non-medical method (e.g., for health enhancement or health supplementation). The medically effective treatment method may be, for example, use as a medicine, pharmaceutical composition, or medical device. The non-medical method may be, for example, use in daily necessities for cancer prevention, prevention of recurrence, or symptom suppression. Daily necessities include medical supplies, foods, beauty products, and decorative items other than those mentioned above.

[0021] The antitumor agent of this embodiment can be used for the treatment of cancer in animals, which may be mammals including humans.

[0022] (Antitumor composition) The antitumor agent of this embodiment can be used alone or mixed with other components for the above-mentioned uses to form an antitumor agent composition. For example, when the antitumor agent is Magnolia maggiore essential oil, it may be used alone or in a mixture with other components, similar to the configuration that has been used conventionally as a fragrance component of Magnolia maggiore essential oil.

[0023] The antitumor composition can be used, for example, as a pharmaceutical composition. The content and intake form (e.g., dosage form) of the pharmaceutical composition can be appropriately selected and are not particularly limited.

[0024] A preferred method of using the antitumor agent composition is to incorporate the antitumor agent components into the air so that the components are inhaled into the human body, such as an animal. The components can be incorporated into the air by spraying the components containing the antitumor agent (for example, an aqueous solution or a liquid containing another solvent) into the air. Alternatively, the components containing the antitumor agent can be dispersed and evaporated into the air, allowing them to be incorporated into the air. The antitumor agent of this embodiment contains the odor component of Magnolia sieboldii, and is therefore particularly suitable because when it is released into the air, it can exert a so-called aroma effect as a fragrance component.

[0025] As a method for scattering and evaporating components containing an antitumor agent into the air, for example, Magnolia maggiore essential oil, which is one form of an antitumor agent, or components containing it can be simply placed in a state where they are exposed to air. For example, the means for placing them in a state where they are exposed to air can be simply placed as an air freshener, deodorant, etc. Furthermore, they can be included in other medical supplies, foods, beauty products, or decorative items.

[0026] Other medical supplies include cloth products such as masks, bandages, towels, etc. For example, a medical mask may be impregnated with the antitumor agent components of the present embodiment, so that the antitumor agent components can be inhaled with each breath. Examples of beauty products include cosmetics, etc. Cosmetics can be selected in any form that can be used by spraying, applying, etc. As an ornament, for example, a space can be provided in the ornament to be worn to store the components of the antitumor agent of this embodiment, and a portion of the space can be provided where it is exposed to air, so that the components can disperse and evaporate into the air around the person wearing it.

[0027] When used, the Magnolia maggiore extract component of this embodiment preferably has a concentration of citral in the air as a liquid component of 1.0 pL / ml or more, more preferably 5.0 pL / ml or more, even more preferably 10.0 pL / ml or more, and particularly preferably 14.3 pL / ml or more. When the treated organism is exposed to air containing this concentration of citral, it has a significant anti-tumor effect on the organism. As a guideline, it is preferable to use a solution obtained by diluting the undiluted Magnolia maggiore essential oil with another solvent to a concentration of more than 500 times, preferably more than 300 times. At these concentrations, the antitumor effect can be sufficiently exerted when exposed to air.

[0028] (Effects of this embodiment) According to this embodiment, it is possible to provide an antitumor agent, pharmaceutical composition, and antitumor composition that have a high antitumor effect even in a small amount, are highly safe for the human body, and have a wide range of applications compared to compositions containing fragrance components. The inventors have demonstrated that the volatile components of Magnolia miltiorrhiza essential oil exhibit a strong antitumor effect on tumor cells, particularly breast cancer cells. There are no other research reports on the antitumor effect of Magnolia miltiorrhiza, and this is thought to lead to new drug development.

[0029] Although the embodiment of the present invention has been described above, the present invention is not limited to the above embodiment and various modifications can be made. [Example]

[0030] The effects of the present invention will be made clearer by the following examples and comparative examples. Note that the present invention is not limited to the following examples, and can be practiced by making appropriate changes within the scope of the present invention.

[0031] (Test Example 1) (Effect of Magnolia sieboldii essential oil on mouse breast cancer cells) Magnolia maggiore essential oil is used as a fragrance and air freshener, and its components volatilize and evaporate into the air even when the oil is left standing. First, we investigated whether tumor cells are affected by air containing Magnolia maggiore essential oil components.

[0032] The Magnolia sieboldii essential oil used was prepared by Seiplus Corporation using a common steam distillation method. Magnolia maggiore essential oil, an extract of Magnolia maggiore, was placed in the central well of a 96-well plate. Cultured mouse breast cancer cells (4T1) were placed in the surrounding wells, and the plate was then covered and left to stand. Each well was connected by the space above, allowing only evaporated components to reach the other wells, but it is thought that the further away from the central well the more the amount (concentration) of Magnolia maggiore essential oil components reached. After 48 hours of incubation, an MTT assay was performed to measure cell proliferation and cell death, and the tumor growth inhibitory effect on the cancer cells in each well was assessed using an MTT cell proliferation assay kit (Roche Diagnostics, Tokyo, Japan) according to the attached protocol.

[0033] FIG. 1 is a photograph showing the results of an MTT assay that verified the effect of Magnolia sieboldii essential oil on mouse breast cancer cells. DMSO, Magnolia kobus essential oil, or Magnolia kobus essential oil diluted to various concentrations with DMSO was added to the two central wells shown as CW in (a). 4T1 cultured cells (1 × 10 cells per well) were added to all surrounding wells. 4 ) were placed in the wells. In the central well CW, DMSO was placed in (a), Magnolia sieboldii essential oil (undiluted x 1) in (b), 100x diluted in (c), 300x diluted in (d), and 500x diluted in (e). In the MTT assay, wells in which cancer cells were actively growing were stained navy blue (dark in the image), while wells in which growth had stopped and cell death had been induced turned yellow (light in the image). In the image, the distance between the centers of the wells was 1 cm.

[0034] As shown in the figure, when undiluted Magnolia maggiore essential oil was placed (b), all 4T1 cells on the plate ceased activity and went into cell death. As shown in (c) to (e), this activity decreased concentration-dependently when the Magnolia maggiore concentration was lowered, and when it was diluted 500-fold, the cell death-inducing activity almost disappeared. Furthermore, as shown in (c) to (e), this activity also decreased distance-dependently.

[0035] Here, in (a), the concentration of the aromatic component citral in the air near the essential oil ×1 was measured and found to be 4.3 nL / ml. (d) shows that if the concentration falls below 1 / 300 of this level, the cancer cell-killing activity significantly decreases when the distance from the essential oil exceeds 1 cm. Therefore, it is considered particularly preferable that the concentration of essential oil with sufficient activity be equal to or greater than (1 / 300 of 4.3 nL / ml), i.e., 14.3 pL / ml or greater, when converted to the concentration of citral in the air.

[0036] Furthermore, an MTT assay was performed using 300-fold diluted Magnolia malvaceae essential oil to further examine the relationship between distance from the essential oil and cancer cell viability. Figure 2 is a graph analyzing the relationship between distance from essential oil and cancer cell viability. The horizontal axis indicates distances of 1.0 cm proximal, 2.0 cm middle, and 3.0 cm distal (***p<0.005). As shown in the figure, the survival rate of 4T1 cells increased significantly with increasing distance from the essential oil.

[0037] (Test Example 2) (IC50 measurement of Magnolia sieboldii essential oil) Next, Magnolia sieboldii diluted to various concentrations was reacted with 4T1 cells, and an MTT assay was performed 48 hours later. Figure 3 is a photograph showing the results of an MTT assay that examined the effect of various concentrations of Magnolia maggiore essential oil on mouse breast cancer cells. In the figure, the position of each well corresponds to the approximate dilution factor (the factor by which the essential oil was diluted with DMSO). The test method was the same as in Test Example 1, except for the concentration. Based on the results obtained, the tumor growth inhibitory effect of Magnolia sieboldii was quantified (IC50 value).

[0038] Figure 4 is a graph showing the quantification results of the tumor growth inhibitory effect of Magnolia miltiorrhiza essential oil. As shown in the figure, the IC50 value of Magnolia miltiorrhiza essential oil against 4T1 cells was 0.105 μg / ml.

[0039] (Test Example 3) (Cell death induction effect of Magnolia sieboldii transpiration components) Next, the changes occurring in cancer cells (4T1) reacted with the evaporated components of Magnolia sieboldii essential oil were observed under a fluorescence microscope. 4T1 cells (cell number: 1 × 10 4 ) were treated with Magnolia sieboldii essential oil (x300) for 48 hours, and live cells were fluorescently stained with green (Calcein-AM) (light color in the figure) and dead cells with red (PI) (light color in the figure).

[0040] Figure 5 is a photograph of fluorescent staining showing the cell death induction effect of 4T1 cells reacted with the volatilized components of Magnolia maggiore essential oil. (a) shows the control (DMSO), and (b) shows cells treated with Magnolia maggiore essential oil (x300). As shown in (b), the cancer cells shrank in size and nuclear aggregation was observed after treatment with Magnolia maggiore essential oil. These results demonstrate that the volatilized components of Magnolia maggiore essential oil induce cell death in cancer cells.

[0041] (Test Example 4) (Antitumor effect of Magnolia kobus essential oil on a mouse tumor-bearing model) The antitumor effects of Magnolia sieboldii essential oil were examined in vivo using a mouse tumor-bearing model. 2x10 subcutaneous injections into the dorsum of 30 mice 5 Mice were transplanted with 4T1 breast cancer cells. These mice were divided into two groups (MS and control). Mice in the MS (M. salicifolia) group were placed in a semi-enclosed room and exposed to the scent of Magnolia sieboldii (citral concentration in the air: 4.3 nL / ml) for 8 hours per day while breathing naturally. Mice in the control group were placed in a standard room and allowed to breathe naturally. After 5 weeks, the mice from both groups were sacrificed, and their weights were compared. The tumors were then excised and the tumor areas and weights were compared.

[0042] Figure 6 shows the body weights of mice in both the MS (inhalation of Magnolia maggiore essential oil components) and control groups. (a) is a photograph of mice in both groups. (b) is a graph comparing the body weights of both groups. There was no change in the photographic appearance of the control and MS mice, and no significant difference in weight was observed. In other words, no effect on the health status of the MS group was confirmed.

[0043] Figure 7 shows the tumors excised from mice in both groups. (a) is a photograph of the tumors excised from both groups. (b) is a graph comparing the tumor area of ​​the excised tumors from both groups. (c) is a graph comparing the tumor weight of the excised tumors from both groups. (a) Tumor growth was observed in 14 out of 15 mice (93%) in the control group, whereas in the MS group, this was reduced to 7 out of 15 (47%). (b) and (c) show that the area and weight of the excised tumors were significantly reduced in the MS group compared to the control group. These results demonstrate that inhaling the vaporized gas from Magnolia sieboldii suppresses tumor growth without harming the health of mice.

[0044] (Test Example 5) (Component analysis of Magnolia sieboldii essential oil) The constituents of Magnolia sieboldii essential oil were analyzed using gas chromatography. The results showed that it contained large amounts of 1,8-cineole (18.50%), neral (10.66%), geranial (15.09%), and trans-anethole (9.99%). Neral and geranial are optical isomers, and the combination of these is called citral. These results showed that the most abundant component in Magnolia sieboldii essential oil was citral (citral, 25.75%), followed by 1,8-cineole (1,8-cineole, 18.50%).

[0045] (Test Example 6) (Component analysis of Magnolia sieboldii essential oil) To compare the antitumor effects of citral and 1,8-cineole, which are abundant in Magnolia miltiorrhiza essential oil, chemically synthesized compounds were reacted with 4T1 cells, and MTT assays were performed 48 hours later. These assays were performed in the same manner as in Test Example 1, except that citral and 1,8-cineole were used instead of Magnolia miltiorrhiza essential oil. 8 is a photograph showing the results of an MTT assay for the antitumor effects of citral and 1,8-cineole, where (a) shows the results for citral and (b) shows the results for 1,8-cineole.

[0046] From the obtained results, the tumor growth inhibitory effects of citral and 1,8-cineole were quantified (IC50 value). Quantification was performed in the same manner as in Test Example 2. 9 is a graph showing IC50 quantification for the antitumor effects of citral and 1,8-cineole, where (a) shows the results for citral and (b) shows the results for 1,8-cineole. These results showed that the IC50 value of citral was 0.193 μg / ml, while that of 1,8-cineole was 1.711 μg / ml, approximately 10 times higher. These results indicate that citral plays the most important role in the antitumor effect of Magnolia kobushi essential oil.

[0047] (Test Example 7) (Anti-tumor mechanism of citral) The results so far have shown that Magnolia sieboldii essential oil contains the most citral, and that it has a strong antitumor effect. When breast cancer cells were administered citral equivalent to the IC50, cell movement slowed down after 12 hours, and was almost completely stopped by 16 hours. To analyze the changes in proteins occurring in breast cancer cells at this time, a Western blot experiment was performed. Citral was added to breast cancer cells at concentrations of 0.19 μg / ml and 1.9 μg / ml (IC50 values), and the cells were incubated for 14 hours. After the incubation, proteins were extracted from the breast cancer cells and subjected to Western blot analysis at the same concentration.

[0048] FIG. 10 is a photograph of a Western blot showing the effect of citral on each protein in breast cancer cells. As shown in the figure, it was revealed that caspase 3 and caspase 9 were cleaved and activated with increasing doses of citral. Bax also decreased, and the amount of cytochrome C increased. Meanwhile, the amount of Bcl-2, which is thought to have an inhibitory effect on cell death, increased. The expression of p53, p21, and p27, which are involved in the cell cycle, all decreased slightly. These results suggest that the mechanism by which citral induces cell death is through its action on Bax present on the mitochondrial membrane of cancer cells, which reduces the mitochondrial membrane potential, promoting the release of cytochrome C into the cytoplasm and activating capase 3 and caspase 9. These results suggest that in addition to the mitochondrial-mediated apoptosis reaction, cell cycle arrest may also be involved.

[0049] These results suggest that Magnolia miltiorrhiza essential oil has an antitumor effect against mouse breast cancer cells (4T1), with an IC50 of 105ng / ml. The antitumor factors of Magnolia miltiorrhiza essential oil are present in its vaporized components, and the effect decreased distance-dependently. Magnolia miltiorrhiza contains large amounts of low-molecular-weight compounds, such as citral, 1,8-cineole, and trans-anethole. Citral, the most abundant compound in Magnolia miltiorrhiza, showed a strong antitumor effect. Furthermore, it was shown that the mechanism of citral-induced cell death is due to the release of cytochrome c and the activation of caspases 3 and 9 following a decrease in mitochondrial membrane potential mediated by Bax.

[0050] (Test Example 8) (Anti-tumor effect against various tumor cells) The antitumor effect of the antitumor agent of this embodiment was examined on mouse 4T1 cells as well as human breast cancer cells (MCF7), human gastric cancer cells (MKN45), and human colon cancer cells (DLD1). 1 μg / ml of Magnolia sieboldii essential oil was added to each cell and reacted for various periods of time, after which an MTT assay similar to that in Test Example 1 was carried out to examine the cell viability.

[0051] Figure 11 is a graph showing the cell viability of each cell type in the presence of an antitumor agent. In the figure, (a) shows breast cancer cells (MCF7), (b) shows gastric cancer cells (MKN45), and (c) shows colon cancer cells (DLD1). The number of cells in the control (in the absence of an antitumor agent) is set at 100, and the percentage of viability over time is shown. As shown in the figure, the cell viability of all cells decreased in a time-dependent manner in the presence of Magnolia maggiore essential oil. These results demonstrate that the antitumor agent of this embodiment has antitumor activity not only against mouse breast cancer cells as in the previous test example, but also against human cancer cells, and against breast cancer, gastric cancer, and colon cancer. Based on these results, it is believed that the antitumor agent of this embodiment can be used to treat these cancers.

[0052] Although the embodiments of the present invention have been described above, these embodiments are presented as examples and are not intended to limit the scope of the invention. These embodiments can be embodied in various other forms, and various omissions, substitutions, and modifications can be made without departing from the spirit of the invention. These embodiments and their modifications are included within the scope and spirit of the invention, as well as within the scope of the invention and its equivalents as defined in the claims. [Industrial Applicability]

[0053] According to the present invention, it is possible to provide an antitumor agent, a pharmaceutical composition, and an antitumor composition that have a high antitumor effect even in a small amount, are highly safe for the human body, and have a wide range of applications compared to compositions containing fragrance components.

Claims

1. An antitumor agent containing extracts from Magnolia sieboldii.

2. The antitumor agent according to claim 1, comprising citral or 1,8-cineole.

3. The antitumor agent according to claim 1 or 2, wherein the extract component of Magnolia nigricans is Magnolia nigricans essential oil or an extract thereof.

4. The antitumor agent according to claim 1 or 2, which is for treating breast cancer, colon cancer, pancreatic cancer, esophageal cancer or gastric cancer.

5. A pharmaceutical composition comprising the antitumor agent according to claim 1 or 2.

6. An antitumor composition comprising the antitumor agent according to claim 1 or 2, for inclusion in an air freshener or deodorant.

7. An antitumor composition comprising the antitumor agent according to claim 1 or 2, for inclusion in a medical product, food product, cosmetic product or decorative product.

8. 3. An antitumor composition comprising the antitumor agent according to claim 1 or 2, which is sprayed or evaporated into the air and inhaled into the human body.

9. 3. An antitumor composition comprising the antitumor agent according to claim 1 or 2, which is used by spraying or evaporating so as to contain 1.0 pL / ml or more of citral in the air.

Citation Information

Patent Citations

  • Compositions and methods for treating solid and soft tissue tumors and proliferative disorders

    JP2023522299A