KR101880295B1 - Composition comprising dihydroergotamine tartrate for preventing or treating lung cancer - Google Patents

Abstract

The present invention relates to a composition for preventing or treating lung cancer comprising dihydroergotamine tartrate. Dihydro-ergotamine tart rate in accordance with the present invention reduces the permeability of the mitochondrial membrane and lung cancer cells, by increasing the ROS reduces the ATP produced, and thus the damaged mitochondria release the apoptotic cytochrome c (apoptotic cytochrome c) Since it is removed by autophagy, it can inhibit the proliferation and tumor formation of lung cancer cells, and thus can be usefully used for prevention and treatment of lung cancer.

Description

[0001] The present invention relates to a composition for preventing or treating lung cancer comprising dihydroergotamine tartrate,

The present invention relates to a composition for preventing or treating lung cancer comprising dihydroergotamine tartrate.

Lung cancer is less common than other cancers, but it is known to have the highest mortality rate among cancer patients. Lung cancer is a cancer that is difficult to diagnose early, and its characteristics are easily metastasized to surrounding organs or lymph nodes. The prognosis is worse than other cancers. Despite efforts to treat lung cancer, And mortality from lung cancer has continued to rise, making it the fifth leading cause of cancer deaths. According to data released by the Ministry of Health and Welfare's Cancer Registration Division, the mortality rate within one year after the onset of lung cancer is estimated to account for about 80% of lung cancer patients, and the survival rate of lung cancer patients is also very low. Although chemotherapy and radiotherapy have been used for the treatment of lung cancer, the therapeutic effect is very low. In the case of gemcitabine, the most commonly used anticancer drug for lung cancer, its efficiency as a pyrimidine antagonist is 6- (11%), which is used in combination with other drugs such as oxalate and 5-fluorouracil (5-FU), but it does not affect the significant survival rate of patients with lung cancer. In fact, gemcitabine has not been shown to have a significant impact on the survival rate of patients with lung cancer, despite being approved for use in lung cancer, suggesting that new drugs that can treat lung cancer and new dosing therapies And the like.

On the other hand, dihydroergotamine tartrate is a compound derived from ergot alkaloids and is mainly used for migraine. Ergotamine tartrate (ET) is an ergot fungus, Claviceps The first ergot alkaloid isolated from purpurea , DHE was synthesized from ergotamine.

Mitochondria (mitochondria) are one of the subcellular organelles that form the backbone of energy metabolism in cells, surrounded by a nuclear membrane that is characteristic of eukaryotic cells. Mitochondria produce adenosine triphosphate (ATP), the most cellular energy required for cells. This process of ATP production is called cell respiration and it is activated as the respiration becomes active. Mitochondria not only supply the energy needed for cells, but are also involved in various regulatory processes such as signal transduction, cell differentiation, and cell death. Mitochondrial mitophagy is a type of autophagy, a programmed cell death, which means that the mitochondria are self-predominant.

The present inventors have conducted studies to develop a composition for the prophylactic or therapeutic treatment of lung cancer and found that dihydroergotamine tartrate damages the mitochondria of lung cancer cells and thereby induces apoptosis and autophagy in lung cancer cells And thus the present invention has been completed.

European Patent EP0865789 U.S. Published Patent Application No. US2014 / 0065219

It is an object of the present invention to provide a composition for preventing or treating lung cancer comprising dihydroergotamine tartrate.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating lung cancer comprising dihydroergotamine tartrate.

The present invention also provides a food composition for preventing or ameliorating lung cancer comprising dihydroergotamine tartrate.

Dihydro-ergotamine tart rate in accordance with the present invention reduces the permeability of the mitochondrial membrane and lung cancer cells, by increasing the ROS reduces the ATP produced, and thus the damaged mitochondria release the apoptotic cytochrome c (apoptotic cytochrome c) Since it is removed by autophagy, it can inhibit the proliferation and tumor formation of lung cancer cells, and thus can be usefully used for prevention and treatment of lung cancer.

FIG. 1 is a graph showing cell proliferation of DHE-treated A549, NCI-H226, or NCI-H460 cells in order to examine the effect of the DHE of the present invention on the proliferation of lung cancer cells.
FIG. 2 shows the result of analysis of DHE-treated A549 cells by SRM and JC-1 labeled cells using CLSM and FACS in order to confirm the influence of DHE of the present invention on the morphology and membrane potential of mitochondria Fig.
FIG. 3 is a graph showing the results of observing ROS generation, ATP production, and cytochrome c release in A549 cells treated with DHE to confirm the effect of DHE of the present invention on the function of mitochondria in A549 cells.
FIG. 4 is a graph showing the results of observing DHE-treated A549 cells using Western blotting, CLSM, and TEM in order to confirm the effect of DHE of the present invention on autopatching in A549 cells.
FIG. 5 is a graph showing the results of observing lung cancer formation and lung cancer cell proliferation after transferring DHE to K- ras ^LA1 , a lung cancer model mouse, in order to examine the effect of DHE of the present invention on lung cancer formation and lung cancer cell proliferation to be.
6 is a the DHE of the present invention showing a result of observation using a, Western blot, and the closing of the TEM K- ras mice ^LA1 passes the DHE to identify the effect on the macrophages in the self-K- ras ^LA1 mouse.
FIG. 7 is a graph showing the results of observation of the lungs of K- ras ^LA1 mice transfected with DHE using Western blot and TUNEL assay to confirm the effect of DHE of the present invention on apoptosis in K- ras ^LA1 mouse Fig.

The present invention provides a composition for preventing or treating lung cancer comprising dihydroergotamine tartrate as an active ingredient.

The composition comprises a pharmaceutical composition and a food composition.

Hereinafter, the present invention will be described in detail.

Dihydroergotamine tartrate, an active ingredient of the present invention, is a compound derived from ergot alkaloids, which can be synthesized from ergotamine and is represented by the following formula (1).

[Chemical Formula 1]

The dihydro-ergotamine tart rate is decreased mitochondrial membrane permeability of cancer cells and, by increasing the ROS reduces the ATP produced, and thus the damaged mitochondria release the apoptotic cytochrome c (apoptotic cytochrome c) Since it is removed by autophagy, it inhibits the proliferation and tumor formation of lung cancer cells.

The lung cancer may be non-small cell lung cancer or small cell lung cancer, preferably non-small cell lung cancer.

The non-small cell lung cancer includes lung cancer, squamous cell cancer or large cell cancer, preferably lung cancer.

The pharmaceutical composition according to the present invention may contain other ingredients such as dihydroergotamine tartrate and the like which can give a synergistic effect to the main effect within a range not impairing the intended main effect of the present invention have.

In addition, the pharmaceutical composition of the present invention may further comprise pharmaceutically acceptable carriers, excipients and diluents in addition to the above-described effective ingredients for administration.

Examples of the carrier, excipient and diluent include lactose, textol, 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, mineral oil.

The pharmaceutical composition of the present invention may be prepared in various parenteral or oral dosage forms according to known methods, preferably formulated as an aerosol and administered to an individual through inhalation.

Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch, calcium carbonate, sucrose or lactose, gelatin, . In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweetening agents, fragrances, preservatives and the like may be included in addition to commonly used simple diluents such as water and liquid paraffin. have.

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solution and suspension include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include withexol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The effective dose of the pharmaceutical composition of the present invention may vary depending on the age and gender of the patient, but it may be 0.0001 to 100 mg / kg, preferably 0.001 to 10 mg / kg.

The composition of the present invention can be used alone or in combination with methods using surgery, chemotherapy, radiotherapy, hormone therapy, drug therapy and biological response modifiers for the prevention or treatment of lung cancer.

When the dihydroergotamine tartrate of the present invention is used as a food additive, the dihydroergotamine tartrate may be used as it is, or it may be suitably used according to a conventional method such as being mixed with another food or food ingredient have.

In addition, the amount of the dihydroergotamine tartrate, which is an active ingredient, may be suitably changed according to the intended use (preventive, health or therapeutic treatment), and the dihydroergotamine tartrate may be added to the total weight of the food composition But it is not limited thereto. If the content is less than 0.001% by weight, the improvement effect may be insignificant. If the content is more than 50% by weight, the increase rate of the effect relative to the usage amount may not be economical.

As a specific example, the dihydroergotamine tartrate of the present invention is added in an amount of not more than 15% by weight, preferably not more than 10% by weight based on the raw material, when the food or beverage is produced. However, when it is intended for health and hygiene purposes or for the purpose of controlling health, it can be added in an amount below the above range, and there is no problem in terms of safety. Therefore, the active ingredient can be used in an amount exceeding the above range have.

Examples of foods to which the dihydroergotamine tartrate of the present invention can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, , Beverages, tea, drinks, alcoholic beverages, vitamin complexes, and the like, and includes, but is not limited to, all conventional health foods.

When the food composition of the present invention is prepared as a beverage, it may contain additional ingredients such as various flavors or natural carbohydrates such as ordinary beverages. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharin and aspartame, and the like. The natural carbohydrate is contained in an amount of 0.01 to 10% by weight, preferably 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.

In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , Carbonating agents used in carbonated beverages, and the like. In addition, the compositions of the present invention may include flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of the above additives is not limited to a great extent, but may be in the range of 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the examples.

Example 1. Preparation of materials

1-1. Preparation of samples and antibodies

The dihydroergotamine tartrate (DHE) used in the present invention is commercially available from Tokyo Chemical Industry Co., Ltd. (TCI). Cytochrome c, HSP60, PCNA and actin antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA) and anti-PINK1, DRP1 and Parkin were obtained from Abcam (Cambridge, MA, USA). Antibodies against LC3B and caspase-3 were purchased from Cell Signaling Technology (Beverly, MA, USA). GAPDH (glyceraldehyde 3-phosphate dehydrogenase) and α-tubulin antibodies were purchased from AbFrontier (Seoul, Korea).

1-2. Cell culture of lung cancer cell line

In the human lung cancer cell lines (A549, NCI-H226, and NCI-H460) the ATCC humidified incubator of were obtained from (American Type Culture Collection, Rockville, MD, USA), this _{37 ℃, 5% CO 2,} 10% fetal bovine Were cultured in Hams F-12 (A549) or RPMI-1640 (NCI-H226 and NCI-H460) medium containing serum (FBS) and 1% penicillin / streptomycin (P / S).

1-3. Experimental design using lung cancer animal model

DHE (0.5 mg / Kg or 1 mg / Kg) was delivered to the 10-week-old K- ras ^LA1 male mice, a lung cancer animal model, by the aerosol method through the nose for four weeks twice a week. Cisplatin was injected intravenously (4 mg / Kg) once a week as a positive control for lung cancer drug therapy. As a negative control group, only the carrier group was used in addition to the control group (control group).

Experimental Example  One. DHE  Identification of the effect on proliferation of lung cancer cells

To confirm the effect of DHE on the proliferation of A549, NCI-H226, or NCI-H460 lung cancer cells, real-time cell proliferation and survival were analyzed using xCELLIGENCE for 72 hours after treatment. Specifically, A549, NCI-H226, or NCI-H460 lung cancer cells (2 × 10 ³ ) were treated with 5 or 10 μM of DHE in an E-plate 16-well (Roche Applied Science, Indianapolis, IN, USA) Cell proliferation was observed for 72 hours using the RTCA DP system (Roche Applied Science), which is shown in Fig.

As shown in FIG. 1, 10 μM of DHE significantly reduced cell proliferation compared to control or DMSO (vehicle) group treated with nothing in A549, NCI-H226, or NCI-H460 cells. More specifically, for 72 hours, 10 μM DHE reduced cell viability by 36.8%, 65.2%, and 66.4% for A549, NCI-H226, and NCI-H460, respectively, compared to the DMSO group, ₅₀ were 13.6 [mu] M, 7.67 [mu] M, and 6.74 [mu] M, respectively.

Experimental Example 2. Effect of DHE on morphology and membrane potential of mitochondria

To determine the effect of DHE on the mitochondrial morphology of A549 cells, A549 cells were cultured in 2-well chamber slides and treated with 10 μM DHE. After 72 hours of incubation, the cells were incubated with 2 μg / ml JC-1 (5,5,6,6-tetrachloro-1,1,3,3-tetraethyl benzimidazolylcarbocyanine iodide; Molecular Probes) The labeled cells were washed with PBS (phosphate buffered saline). For morphological analysis, fluorescence was traced using SRM (super resolution microscopy) to confirm the image of mitochondria and to analyze the size of relative mitochondria. The above results are shown in Fig.

As shown in FIG. 2A, the DHE treatment showed the fragmentation of mitochondria in lung cancer cells, and the length of mitochondria was significantly reduced in DHE-treated cells as compared with the control and DMSO treated cells Respectively.

In order to confirm the membrane potential of mitochondria in DHE-treated A549 cells, membrane potential analysis of JC-1 labeled mitochondria was performed using Image J software (version 1.48, National Institutes of Health, Bethesda, MD, USA) , And the results are shown in Fig. 2B. The JC-1 dye induces a reversible change in fluorescence emission from green to red as the mitochondrial membrane potential increases. Cells with high membrane potential exhibit red fluorescence induced by dye agglutination, while cells with low membrane potential exhibit green fluorescence induced by monomeric JC-1, so the red / green ratio indicates the state of mitochondria.

As shown in Figure 2b, the red / green ratio of DHE treated cells was significantly reduced compared to the red / green ratio of control or DMSO treated cells. Indicating that DHE induces morphological changes and dysfunction of mitochondria in lung cancer cells.

Experimental Example  3. DHE  Effect on function of mitochondria

In order to confirm the effect of DHE on the function of mitochondria in A549 cells, ROS development, ATP production, and cytochrome c release were evaluated.

First, to measure the development of ROS, A549 cells were incubated with 5 or 10 [mu] M DHE for 72 hours. After incubation, the cells were washed with PBS and incubated with 10 [mu] M H ₂ -DCFDA (2,7-dichlorodihydrofluorescein diacetate, Molecular Probes) for 30 min under 37 ° C dark conditions. A sample containing 1 x 10 ⁴ cells stained with H ₂ -DCFDA was analyzed by fluorescence-activated cell sorting (FACS), which is shown in FIG.

As shown in Fig. 3A, it was confirmed that ROS levels were significantly increased in cells treated with 10 [mu] M of DHE compared with the control or DMSO treated cells.

In addition, to measure ATP production, A549 cells were grown in 96-well plates and treated with 5 or 10 [mu] M DHE for 72 h. After treatment, CellTiter-Glo Reagent (Promega Corporation, Madison, Wis., USA) was added to each well in the same volume as the cell culture medium volume (100 μL). The solution was mixed for 2 minutes and further incubated for 10 minutes to stabilize the fluorescence signal. The generated signals were recorded using a microplate luminometer Orion II (Berthold Detection Systems GmbH, Pforzheim, Germany), which is shown in FIG. 3b.

As shown in Figure 3b, a significant deficiency of ATP was observed in DHE treated cells as compared to control or DMSO treated cells.

Also, in order to measure cytochrome c release in cells treated under the same conditions as above, Western blot and CLSM were used to analyze them, which are shown in FIGS. 3C and 3D, respectively.

As shown in Figures 3c and 3d, ATP-deficient cells released DHT-treated cytochrome c from mitochondria into cytoplasm and compared cytochrome c of cells treated with 10 [mu] M DHE compared to control or DMSO treated cells And the release was markedly increased.

Experimental Example  4. DHE Self-predation  Impact

Western blot, CLSM, and transmission electron microscopy (TEM) were used to confirm the effect of DHE on autopoiesis in A549 cells.

First, A549 cells were cultured on a 2-well chamber slide and treated with 10 μM DHE for 72 hours. The cultured cells were labeled with 100 nM of MitoTracker and 2 μl / ml of Cyto-ID Green Detection Reagent (Enzo Life Sciences, Farmingdale, NY, USA) for 30 min under the dark condition at 37 ° C., ≪ / RTI > and fixed in 4% PFA at 37 C for 10 minutes. Proteins were separated from the DHE-treated A549 cells and subjected to western blot analysis using antibodies against PINK1, Parkin, and LC3B, as shown in FIG. 4A.

As shown in FIG. 4A, autophosphorylation of PINK1, overexpression of Parkin and LC3B II was confirmed in DHE-treated cells.

In addition, CLSM analysis of the DHE-treated A549 cells was performed, which is shown in FIG. 4B.

As shown in Figure 4b, increased autophagic dots of mitochondria in DHE treated cells were identified.

In addition, the DHE-treated A549 cells were further analyzed by TEM and are shown in FIG. 4C.

As shown in FIG. 4C, when A549 cells were treated with DHE, the cristae structure of mitochondria (orange arrow, middle drawing) was destroyed, and self-predation was induced (red arrow, the drawing below).

Experimental Example  5. DHE  Identification of the effects of animal models on lung cancer formation and lung cancer cell proliferation

As in Example 1-3, DHE (0.5 mg / Kg or 1 mg / Kg) was delivered to K- ras ^LA1 , a lung cancer model mouse, by aerosol method for 4 weeks, and lung cancer formation and proliferation of lung cancer cells were observed. After the experiment, mice were sacrificed and the lungs were separated and observed with the naked eye. In addition, H & E staining was performed according to a known method after producing lung tissue sections, and western blotting was performed using an antibody against PCNA, which is a cell growth marker. The above experimental results are shown in Figs. 5A to 5C, respectively.

As shown in FIGS. 5A and 5B, the number of tumors (red dotted lines) in lungs of lung cancer model mice delivered with DHE (0.5 mg / Kg or 1 mg / Kg) was significantly reduced compared with the control or vehicle control group, And the degree of lung cancer formation was decreased.

In addition, as shown in FIG. 5C, it was confirmed that the expression amount of PCNA in the lung of lung cancer model mice to which DHE (0.5 mg / Kg or 1 mg / Kg) was delivered was decreased as compared with the control or vehicle control group. These results demonstrate that DHE inhibits lung cancer formation in lung cancer model mice and inhibits the proliferation of lung cancer cells.

Experimental Example  6. DHE  In animal models Self-predation  Impact

DHR (0.5 mg / Kg or 1 mg / Kg) was delivered to K- ras ^LA1 , a lung cancer model mouse, by the aerosol method for 4 weeks as in the case of Example 1-3. Then, lung tissue was separated and DPR1, Western blotting was performed using antibodies against PINK1, Parkin, and LC3B II and transmission electron microscopy (TEM) analysis was performed. The above experimental results are shown in Figs. 6A to 6C, respectively.

As shown in Figure 6a, overexpression of DRP1, PINK1, Parkin, and LC3B II was observed in the lungs of lung cancer model mice delivered with DHE (0.5 mg / Kg or 1 mg / Kg) as compared to the control or vehicle control group.

In addition, as shown in FIGS. 6B and 6C, the formation of a double membrane (red arrow), which is an initial phenomenon of self-predation around the mitochondria in lungs of a lung cancer model mouse delivered with DHE (0.5 mg / Kg or 1 mg / Respectively.

Experimental Example 7. Effects of DHE on apoptosis in animal models

As in Example 1-3, DHE (0.5 mg / Kg or 1 mg / Kg) was delivered to K- ras ^LA1 , a lung cancer model mouse, by aerosol method for 4 weeks. Then, lung tissue was separated and kBax, Cytochrome c, and Caspase-3, and performed TUNEL assay. The above experimental results are shown in Figs. 7A and 7B, respectively.

As shown in FIG. 7A, overexpression of Bax, Cytochrome c, and Caspase-3 was observed in lungs of lung cancer model mice delivered with DHE (0.5 mg / Kg or 1 mg / Kg).

In addition, as shown in Fig. 7 (b), tumor cell death (dark brown) increase in lungs of lung cancer model mice delivered with DHE (0.5 mg / Kg or 1 mg / Kg) was confirmed.

Through the above experiment results, dihydro-ergotamine tart rate decreases the mitochondrial membrane permeability of cancer cells and, by increasing the ROS reduces the ATP generation, whereby the mitochondria are apoptotic cytochrome c (apoptotic cytochrome c) damaged in accordance with the present invention To release Since it is removed by mitophagy, it is confirmed that it inhibits the proliferation and tumor formation of lung cancer cells. Thus, it can be seen that dihydroergotamine tartrate can effectively prevent or treat lung cancer.

Hereinafter, a pharmaceutical composition and a pharmaceutical composition for preventing or treating lung cancer comprising the dihydroergotamine tartrate of the present invention as an active ingredient will be described, but the present invention is not limited thereto but is only specifically described .

Formulation Example 1. Preparation of pharmaceutical preparations

1. Powder manufacture

20 mg of dihydroergotamine tartrate, 100 mg of lactose and 10 mg of talt were mixed according to a conventional acid production method and packed in airtight bags to prepare powders.

2. Manufacture of tablets

10 mg of dihydroergotamine tartrate, 100 mg of corn starch, 100 mg of lactose and 2 mg of magnesium stearate were mixed in accordance with a conventional tablet preparation method, followed by tableting according to a conventional preparation method.

3. Capsule preparation

10 mg of dihydroergotamine tartrate, 3 mg of crystalline cellulose, 14.8 mg of lactose and 0.2 mg of magnesium stearate were mixed and filled in gelatin capsules according to a conventional capsule preparation method to prepare capsules.

4. Injection manufacturing

(2 mL), 10 mg of dihydroergotamine tartrate, 180 mg of mannitol, 2,974 mg of sterile distilled water for injection, and 26 mg of Na ₂ HPO ₄ .2H ₂ O according to the usual injection preparation method.

5. Liquid manufacturing

20 mg of dihydroergotamine tartrate, 10 g of isomerized sugar, and 5 g of mannitol were dissolved in purified water in accordance with the usual liquid preparation method, and the lemon flavor was added in an appropriate amount, and the above components were mixed. Then, purified water was further added thereto, adjusted to a total volume of 100 mL, filled in a brown bottle, and sterilized to prepare a liquid preparation.

Formulation Example 2. Preparation of food preparation

1. Health food manufacturing

100 mg of dihydroergotamine tartrate, a proper amount of vitamin A, 70 g of vitamin A acetate, 1.0 mg of vitamin E, 0.13 mg of vitamin B1, 0.15 mg of vitamin B2, 0.5 mg of vitamin B6, 0.2 g of vitamin B12, 10 mg of vitamin C, , Nicotinic amide 1.7 mg, folic acid 50 g, calcium pantothenate 0.5 mg, inorganic mixture q.s., ferrous sulfate 1.75 mg, zinc oxide 0.82 mg, magnesium carbonate 25.3 mg, potassium monophosphate 15 mg, dibasic calcium phosphate 55 mg, citric acid 90 mg of potassium, 100 mg of calcium carbonate and 24.8 mg of magnesium chloride were mixed and granules were prepared and a health food was prepared according to a conventional method. At this time, although the composition ratio of the vitamin and mineral mixture is relatively mixed with the ingredient suitable for health food, it may be arbitrarily modified.

Although the present invention has been described in terms of the preferred embodiments mentioned above, it is possible to make various modifications and variations without departing from the spirit and scope of the invention. It is also to be understood that the appended claims are intended to cover such modifications and changes as fall within the scope of the invention.

Claims (8)

A pharmaceutical composition for preventing or treating lung cancer, comprising dihydroergotamine tartrate represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]

The pharmaceutical composition for preventing or treating lung cancer according to claim 1, wherein the lung cancer is non-small cell lung cancer or small cell lung cancer. The pharmaceutical composition for preventing or treating lung cancer according to claim 2, wherein the non-small cell lung cancer is at least one selected from the group consisting of lung cancer, squamous cell cancer, and large cell carcinoma. The pharmaceutical composition for preventing or treating lung cancer according to claim 1, wherein the dihydroergotamine tartrate damages mitochondria of lung cancer cells to inhibit proliferation of lung cancer cells. The pharmaceutical composition according to claim 1, wherein the formulation of the pharmaceutical composition is an aerosol. 1. A food composition for preventing or ameliorating lung cancer, comprising dihydroergotamine tartrate represented by the following formula (1) as an active ingredient.
[Chemical Formula 1]

The food composition for preventing or improving lung cancer according to claim 6, wherein the lung cancer is non-small cell lung cancer or small cell lung cancer. The composition for preventing or improving lung cancer according to claim 7, wherein the non-small cell lung cancer is at least one selected from the group consisting of lung cancer, squamous cell carcinoma, and large cell carcinoma.

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