KR20240012182A - Composition comprising the cantharidine compound for prevention or treatment of glioblastoma - Google Patents

Abstract

The present invention relates to a composition for preventing or treating glioblastoma containing cantharidin as an active ingredient. Specifically, the present invention relates to a composition for preventing or treating glioblastoma containing a cantharidin compound or a pharmaceutically acceptable salt thereof as an active ingredient. A pharmaceutical composition for the prevention or treatment of a cantharidin compound as an active ingredient, an inhibitor of the activity of Anoctamin, a calcium-dependent chloride ion channel, and a cancer cell line expressing Anoctamin 1 (ANO1). comprising the step of processing a cantharidin) compound. It relates to a method of inhibiting the activity of anogen in vitro and a health functional food for preventing or improving glioblastoma, which contains a cantharidin compound or a salt thereof as an active ingredient.

Description

Composition for preventing or treating glioblastoma comprising cantharidin as an active ingredient {Composition comprising the cantharidine compound for prevention or treatment of glioblastoma}

The present invention relates to a composition for preventing or treating glioblastoma containing cantharidin as an active ingredient.

Among tumors arising from glial cells in the brain, glioblastoma is histologically the most malignant tumor with nuclear atypia, mitotic figures, proliferation of vascular endothelial cells, and necrosis observed. Glioblastoma accounts for the majority of gliomas, is the second most frequently occurring histologically, and is the most frequent malignant tumor occurring in the brain and central nervous system with a 5-year survival rate of only 5%. In , glioblastoma accounts for 15.1% of all brain and CNS primary carcinomas, and cerebral epithelioma accounts for 34.4% of all gliomas.

In addition, glioblastoma is a tumor that grows very quickly, which causes cerebral pressure to rise rapidly, causing headaches, nausea, and vomiting, and adults often experience convulsions. In addition, the function of nearby nerves may deteriorate due to the tumor itself or brain edema accompanying the tumor, resulting in various symptoms such as decreased limb movement, decreased sensation, facial paralysis, language impairment, decreased cognitive function, and left-right differentiation disorder.

The standard primary treatment methods for glioblastoma include surgical therapy and a combination of temozolomide (TMZ), a chemical therapy, and radiation therapy (RT).

According to the NCCN guidelines on central nervous system cancer, TMZ, an alkylating agent, is currently known to be the standard treatment along with postoperative RT for GBM patients with a good prognosis at a young age. However, the patient group to which such standard treatment can be applied is It is a cancer with a very limited prognosis after treatment, with the 5-year survival rate of all glioblastoma patients being less than 5%. In addition, despite treatments including surgery, radiation therapy, and chemotherapy, glioblastoma is highly resistant to treatment, and the prognosis after treatment is poor.

Therefore, there is a need to develop a new treatment that has fewer side effects and can effectively treat glioblastoma.

Meanwhile, cantharidin (1, 2-dimethyl-3, 6-epoxyperhydrophthalic anhydride) is a lipophilic compound traditionally obtained mainly from the body fluids of blister beetles of the family Meloidae. Cantharidin is an odorless, colorless and crystalline solid at room temperature and is known to act as an inhibitor of protein phosphatase 2A and to have foaming activity when applied to the skin. These cantharidins are known to be traditionally used in the treatment of skin conditions, including the treatment of common warts and molluscum.

However, there has been no report yet on the anticancer activity of cantharidin compounds against glioblastoma.

Republic of Korea Public Patent No. 10-2017-0117027 Republic of Korea Public Patent No. 10-2001-0074721

Accordingly, the present inventors confirmed that the cantharidin compound has an excellent effect of inhibiting the activity of Anoctamin1 (ANO1, hereinafter referred to as Anoone), a calcium-dependent chloride ion channel, and has an effect of inhibiting cell migration and metastasis of glioblastoma. By doing so, the present invention was completed by identifying the use of cantharidin compounds as a new anticancer agent for glioblastoma.

Therefore, an object of the present invention is to provide a pharmaceutical composition for preventing or treating glioblastoma, comprising a cantharidin compound or a pharmaceutically acceptable salt thereof as an active ingredient.

Another object of the present invention is to provide an inhibitor of anogen activity, a calcium-dependent chloride ion channel, containing a cantharidin compound as an active ingredient.

Another object of the present invention is to provide a method for inhibiting the activity of Anoctamin 1 (ANO1) in vitro, comprising treating a cancer cell line expressing Anoctamin 1 (ANO1) with a cantharidin compound.

Another object of the present invention is to provide a health functional food for preventing or improving glioblastoma, which contains a cantharidin compound or a salt thereof as an active ingredient.

In order to achieve the object of the present invention as described above, the present invention provides a pharmaceutical composition for preventing or treating glioblastoma, comprising a cantharidin compound or a pharmaceutically acceptable salt thereof as an active ingredient.

In one embodiment of the present invention, the cantharidin compound may have the ability to selectively inhibit the activity of Anoctamin 1 (ANO1).

In one embodiment of the present invention, the cantharidin compound may have the activity of inhibiting cell proliferation, cell migration, or cell metastasis of glioblastoma.

In one embodiment of the present invention, the glioblastoma may express anogen.

Additionally, the present invention provides an inhibitor of anogen activity, a calcium-dependent chlorine ion channel, containing a cantharidin compound as an active ingredient.

In one embodiment of the present invention, the cantharidin compound may inhibit the activity of Anoctamin 1 (ANO1) in glioblastoma expressing the ANO1.

The present invention also provides a method for inhibiting the activity of Anoctamin 1 (ANO1) in vitro, comprising treating a cancer cell line expressing Anoctamin 1 (ANO1) with a cantharidin compound.

In one embodiment of the present invention, the cancer may be glioblastoma.

In addition, the present invention provides a health functional food for preventing or improving glioblastoma, comprising a cantharidin compound or a salt thereof as an active ingredient.

In one embodiment of the present invention, the cantharidin compound may have an anogen-selective activity inhibitory ability.

In one embodiment of the present invention, the cantharidin compound may have the activity of inhibiting cell proliferation, cell migration, or cell metastasis of glioblastoma.

The composition for preventing or treating glioblastoma containing cantharidin as an active ingredient according to the present invention can selectively inhibit ANO 1 in glioblastoma in which calcium-dependent chlorine ion channels are expressed and activated, and It has all the effects of inhibiting cell proliferation, inhibiting cell migration, and inhibiting cell metastasis against cancer cells, and can be usefully used in medicines and health functional foods for the prevention, improvement, or treatment of glioblastoma.

Figure 1 shows the results of measuring the anogen ion channel inhibitory activity of a cantharidin compound. After treating the glioblastoma U251 cell line with 50 uM cantharidin, the glioblastoma U251 cell line was treated with chloride ions in the whole cell state under high-concentration calcium conditions using a patch clamp technique. The results of measuring current density by used.
Figure 2 shows the treatment of cantharidin compounds at different concentrations in the HEK293T cell line expressing ANO1-GFP, and then measuring the current density due to chloride ions in whole-cell state under high-concentration calcium conditions using a patch clamp technique. It shows one result.
Figure 3 shows the results of measuring the current density due to chlorine ions in the whole cell state under high concentration calcium conditions using the patch clamp technique after treating the HEK293T cell line expressing ANO2 with 10uM and 20uM of cantharidin compounds, respectively. .
Figure 4 shows the results of analyzing the degree of cell proliferation 48 hours after treating the glioblastoma U251 cell line with cantharidin compounds at different concentrations.
Figure 5 shows the results of analyzing the degree of cell migration 18 hours after treating the glioblastoma U251 cell line with a cantharidin compound (10uM) and an anogen inhibitor, CaCCinh-A01 (50uM).
Figure 6 shows the results of analyzing metastatic cells 18 hours after treating the glioblastoma U251 cell line with a cantharidin compound (10uM) and an anogen inhibitor, CaCCinh-A01 (50uM).

The present invention is characterized by providing a novel use of a cantharidin compound as an anticancer agent for glioblastoma.

Specifically, the present invention is characterized by providing a pharmaceutical composition for preventing or treating glioblastoma, comprising a cantharidin compound or a pharmaceutically acceptable salt thereof as an active ingredient.

The cantharidin compound is a lipophilic compound obtained from the body fluids of blister beetles of the family Meloidae, and is known to be used in the treatment of skin conditions, but its anticancer activity in glioblastoma has not been studied at all. does not exist.

In this regard, the present inventors confirmed through experiments in the following examples that the cantharidin compound has excellent anticancer activity against glioblastoma.

The cantharidin compound of the present invention is characterized by its ability to selectively inhibit the activity of Anoctamin 1 (ANO1), a calcium-dependent chloride ion channel.

According to one embodiment of the present invention, after treating a glioblastoma cell line with a cantharidin compound and CaCCinh-A01, a conventionally known anogen inhibitor, the anogen activity was analyzed using a patch clamp technique. As a result, the cantharidin compound treatment It was confirmed that the group inhibited the activity of anogen similarly to the CaCCinh-A01 treatment group.

To reconfirm this, the HEK293T cell line expressing ANO1-GFP, in which the expression of the anogen can be confirmed by fluorescence, was treated with cantharidin compounds at different concentrations and then the anogen activity was analyzed using the patch clamp technique. The anogen activity was analyzed in a concentration-dependent manner of the cantharidin compound. It was confirmed that the activity was inhibited.

In addition, according to another embodiment of the present invention, the effect on the activity of ANO2 according to cantharidin compound treatment was analyzed, and it was found that the cantharidin compound had no effect on the ANO2 ion channel.

Meanwhile, the ANO1 is located on chromosome band 11q13 and is known to be involved in salivary gland secretion, cell volume control, sensory nerve control, and intestinal motility. It is highly expressed and hyperactivated in head and neck cancer, breast cancer, and prostate cancer cells. It turned out that there was.

Therefore, the cantharidin compound of the present invention has a selective inhibitory ability against an anogen and can induce anticancer activity of glioblastoma by inhibiting an anogen.

In order to confirm the anticancer activity of the cantharidin compound against glioblastoma, in one embodiment of the present invention, after treating the glioblastoma U251 cell line with the cantharidin compound, changes in cell proliferation, cell migration, and cell metastasis of the glioblastoma cell line were analyzed. As a result, it was confirmed that treatment with cantharidin compounds inhibited cell proliferation of cancer cell lines, inhibited cell migration, and inhibited cell metastasis.

Therefore, the present invention can provide a pharmaceutical composition for preventing or treating glioblastoma, which includes a cantharidin compound or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the cantharidin compound may be a compound represented by the following formula (1), and may be used in the form of a pharmaceutically acceptable salt thereof.

<Formula 1>

In the present invention, the pharmaceutically acceptable salt may be an acid addition salt formed using an organic acid or an inorganic acid. The organic acids include, for example, formic acid, acetic acid, propionic acid, lactic acid, butyric acid, isobutyric acid, trifluoroacetic acid, malic acid, maleic acid, malonic acid, fumaric acid, succinic acid, succinic acid monoamide, glutamic acid, tartaric acid, oxalic acid, citric acid, and glycol. acids, including glucuronic acid, ascorbic acid, benzoic acid, phthalic acid, salicylic acid, anthranilic acid, dichloroacetic acid, aminooxy acetic acid, benzenesulfonic acid, p-toluenesulfonic acid and methanesulfonic acid salts; Inorganic acids include, for example, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, nitric acid, carbonic acid, and boric acid salts. The above-mentioned acid addition salts can be prepared through methods known in the art.

The cantharidin compound contained in the pharmaceutical composition of the present invention can be extracted and purified from natural sources, or can be chemically synthesized and used.

In addition, the pharmaceutical composition of the present invention may be prepared using pharmaceutically suitable and physiologically acceptable auxiliaries in addition to the active ingredients, and the auxiliaries include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, and lubricants. , lubricants or flavoring agents can be used.

For administration, the pharmaceutical composition may preferably be formulated as a pharmaceutical composition containing one or more pharmaceutically acceptable carriers in addition to the active ingredients described above.

The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic, pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, etc. Additionally, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders include, but are not limited to, starch, gelatin, natural sugars such as glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tracacance or sodium oleate, sodium stearate, magnesium stearate, sodium Includes benzoate, sodium acetate, sodium chloride, etc. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, etc.

Acceptable pharmaceutical carriers for compositions formulated as liquid solutions include those that are sterile and biocompatible, such as saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these ingredients can be mixed and used, and other common additives such as antioxidants, buffers, and bacteriostatic agents can be added as needed. In addition, diluents, dispersants, surfactants, binders, and lubricants can be additionally added to formulate injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.

Furthermore, it can be preferably formulated according to each disease or ingredient using a method disclosed by Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA, as an appropriate method in the field.

Additionally, the present invention can provide a method of treating glioblastoma comprising administering a therapeutically effective amount of the cantharidin compound of the present invention or a pharmaceutically acceptable salt thereof to a subject in need thereof.

The “subject” refers to a mammal that is the subject of treatment, observation, or experiment, and preferably refers to a human.

As used herein, the term "therapeutically effective amount" means the amount of an active ingredient or pharmaceutical composition that is believed by a researcher, veterinarian, physician, or other clinician to induce a biological or medical response in a tissue system, animal, or human. This includes amounts that lead to alleviation of the symptoms of the disease or disorder being treated. It is obvious to those skilled in the art that the therapeutically effective amount and frequency of administration of the active ingredient of the present invention will vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by a person skilled in the art, and can be determined based on the type of disease, the severity of the disease, the content of the active ingredient and other ingredients contained in the composition, the type of dosage form, and the patient's age, weight, and general health. It can be adjusted according to various factors, including condition, gender and diet, administration time, administration route and secretion rate of the composition, treatment period, and concurrently used drugs. In the treatment method of the present invention, for adults, the compound of the present invention is preferably administered at a dose of 0.01 mg/kg to 200 mg/kg once or several times a day.

In the treatment method of the present invention, the composition containing the compound of the present invention as an active ingredient is administered through conventional routes through oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or intradermal routes. It can be administered in any way.

In addition, the present invention can provide an inhibitor of anogen activity, a calcium-dependent chloride ion channel, containing a cantharidin compound as an active ingredient.

The cantharidin compound can effectively inhibit or reduce the activity of Anoctamin 1 (ANO1) in glioblastoma expressing Anoctamin 1 (ANO1) in vitro.

In the present invention, the cantharidin compound may have an IC ₅₀ (uM) against an anogen of 2 to 8 uM, and according to one embodiment of the present invention, an IC ₅₀ (uM) against an anogen in a cell line expressing the anogen is It was confirmed to be 6.79uM.

Furthermore, the present invention can provide a food composition for preventing or improving glioblastoma, comprising a cantharidin compound or a salt thereof as an active ingredient. The food composition according to the present invention can be formulated in the same way as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gum, ice cream, vitamin complexes, and health supplements. etc.

For example, when the food composition of the present invention is manufactured into beverages such as drinks, in addition to the extracts or fractions thereof of the plants exemplified above containing the cantharidin compound of the present invention or its salt, citric acid, high fructose corn syrup, sugar, glucose, acetic acid, It may additionally contain malic acid, perilla, various plant extracts, etc.

In addition, the present invention can provide a health functional food for preventing or improving glioblastoma, which contains a cantharidin compound or a salt thereof as an active ingredient.

Health functional food refers to the extract or fraction thereof of the above-mentioned plants containing the compound of the present invention, or the compound itself, added to food materials such as beverages, teas, spices, gum, and confectionery, or encapsulated, powdered, or suspended. It is a food manufactured from food, which means that when consumed, it brings about a specific health effect. However, unlike general drugs, it has the advantage of not having any side effects that may occur when taking the drug for a long period of time as it is made from food. The health functional food of the present invention obtained in this way is very useful because it can be consumed on a daily basis.

In addition, the amount of the active ingredient of the present invention in health foods cannot be uniformly specified as it varies depending on the type of health food being targeted. However, it may be added within a range that does not impair the original taste of the food, and is usually used for the target foods. It is in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight. In addition, in the case of foods in the form of granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight.

Hereinafter, the present invention will be described in more detail through examples. These examples are for illustrating the present invention in more detail, and the scope of the present invention is not limited to these examples.

<Example 1>

Confirmation of inhibition of anogen ion channel activity by cantharidin compounds

Electrophysiological measurements were performed to confirm whether the cantharidin compound has an effect of inhibiting calcium-dependent chloride ion channel (CaCC) activity. For this purpose, the U251 glioblastoma cell line derived from human glioblastoma was spread on a coverslip and 50 μM cantharidin compound was treated with the cell line for 1 hour. At this time, a group treated only with DMSO, a solvent, was used as the control group, and a group treated with CaCCinh-A01, known as an anogen inhibitor, was used as a comparison group. In addition, the cantharidin compound, CaCCinh-A01, and DMSO used in this example were all purchased from Sigma (St Louis, MO).

To activate the CaCC ion channel, fill a glass pipette for electrophysiology measurement with a pipette solution containing high concentration calcium (5mM), bring it close to the cell, and change the membrane potential from -100 to +100 mV in the whole cell state to chloride ions. The current density was measured.

As a result of the analysis, the activity of the chloride ion channel was found to be reduced in the cantharidin compound treatment group (Figure 1A), and in the cantharidin compound treatment group, the current density was higher at a membrane potential of +80 mV compared to the control group (DMSO treatment group). It was found to be reduced by 50% (Figure 1B).

In addition, to reconfirm whether the cantharidin compound inhibits Anoctamin 1 (ANO1), a calcium-dependent chloride ion channel (CaCC), the present inventors administered the cantharidin compound at different concentrations (0.65, 1.25, 2.5, 5, 10, 20 μM) for 1 hour, electrophysiological measurement of CaCC ion channel activity was performed using the same method as above.

As a result, as shown in Figure 2, when cell lines expressing AnoOne were treated with cantharidin compounds at different concentrations, the activity of AnoOne, a calcium-dependent chloride ion channel, was found to be reduced in a concentration-dependent manner.

Through these results, the present inventors found that the cantharidin compound of the present invention can inhibit the activity of Anoctamin 1 (ANO1), which is activated in cancer cells.

<Example 2>

Confirmation of specific inhibition of anogen ion channel activity by cantharidin compounds

To confirm that the cantharidin compound specifically inhibits the activity of Anoctamin 1 (ANO1), HEK293T cell line expressing ANO2 (Anoctamin 2) was treated with the cantharidin compound for 1 hour, and then Electrophysiological measurements were performed as in Example 1.

As a result, as shown in Figure 3, the cantharidin compound of the present invention was found to have no inhibitory activity on the ANO2 ion channel.

Through these results, it was found that the cantharidin compound showed an anogen-specific inhibitory activity among calcium-dependent chloride ion channels.

<Example 3>

Confirmation of inhibition of glioblastoma cell proliferation by cantharidin compound

Next, in order to confirm whether the cantharidin compound has anti-proliferation activity on glioblastoma cell lines, the present inventors treated the U-251 cell line, a human glioblastoma cell line, with the cantharidin compound and analyzed the degree of cell proliferation.

For this purpose, U-25 cells, a human glioblastoma cell line, were cultured in DEME (Dulbecco Modified medium) supplemented with 10% FBS (fetal bovine serum) and penicillin/streptomycin antibiotics at 37°C under 5% carbon dioxide, and treated with cantharidin compounds. The cell proliferation inhibitory effect was measured using the CCK cell proliferation evaluation method. 1,000 U251 cells per well were dispensed in a 96-well plate and cultured for 18 hours, and cantharidin compounds were added at different concentrations (1, 2.5, 5, 10, 25, 50 uM), and at this time, the group treated with DMSO was used as the control group, and the DMS treatment concentration was not to exceed 0.1%. After culturing for 48 hours, according to the manual of Cell Counting Kit-8 (CCK-8) 5 μl of CCK reagent at a concentration of 5 mg/ml was added and reacted for 3 hours, and then the absorbance at 450 nm was measured.

As a result, as shown in Figure 4, it was shown that the proliferation of the glioblastoma U251 cell line was inhibited in a concentration-dependent manner by cantharidin compound treatment, and in the group treated at a concentration of 50uM, cell proliferation was inhibited by more than 70%. , the concentration at which 50% of cell proliferation was inhibited was found to be 6.2uM.

Accordingly, through these results, the present inventors were able to see that cell proliferation of glioblastoma was effectively inhibited even by treatment with a low concentration of cantharidin compound.

<Example 4>

Confirmation of inhibition of glioblastoma cell migration by cantharidin compound

It was confirmed whether the cantharidin compound has the activity of inhibiting cell migration of glioblastoma. The same U251 cell line used in Example 3 was used, and cell mobility was analyzed by wound healing assay. Specifically, ^3.5 . Then, after 18 hours of incubation, photos before and after incubation were obtained and cell migration distance was measured using Image J software to evaluate cell migration ability.

As a result, as shown in Figure 5, cell migration of glioblastoma was more effectively inhibited in the group treated with the cantharidin compound of the present invention at a concentration of 10uM compared to the group treated with CaCCinh-A01, known as an anogen inhibitor, at a concentration of 50uM. It turned out to be possible.

These results mean that the cantharidin compound has the activity of effectively inhibiting not only cell proliferation but also cell migration in glioblastoma.

<Example 5>

Confirmation of inhibition of glioblastoma cell metastasis by cantharidin compound

It was confirmed whether the cantharidin compound has the activity of inhibiting cell metastasis of glioblastoma. For this purpose, the same U251 cell line used in Example 3 was used and analyzed using Transwell assay (Transwell invasion chambers with 8.0 um pore (Corning)). Specifically, after coating the transwell with Growth factor-reduced Matrigel, ^5.5 After culturing for 18 hours, the cells were fixed and stained using the Diff-Quick Stain Kit (Sysmex, Kobe, Japan), photographs were obtained, and metastatic ability was evaluated using the number of metastatic cells using Image J software.

As a result of the analysis, the microscope image after 18 hours of culture is shown in Figure 6A, and the quantitative graph measuring the number of metastasized cells is shown in Figure 6B. In the group treated with 10uM cantharidin compound, glioblastoma cell migration was inhibited by 75%. On the other hand, the group treated with 50uM CaCCinh-A01 showed that glioblastoma cell migration was inhibited by 30%.

Through this, it was found that the cantharidin compound of the present invention has the activity of effectively inhibiting cell metastasis of glioblastoma.

Through the above results, the present inventors have concluded that the cantharidin compound of the present invention can specifically inhibit the activity of anogen, inhibit cell proliferation of glioblastoma, and effectively inhibit both cell migration and cell metastasis. , it was found that it can be used as a new anticancer agent for glioblastoma through selective blocking of anogen.

So far, the present invention has been examined focusing on its preferred embodiments. A person skilled in the art to which the present invention pertains will understand that the present invention may be implemented in a modified form without departing from the essential characteristics of the present invention. Therefore, the disclosed embodiments should be considered from an illustrative rather than a restrictive perspective. The scope of the present invention is indicated in the claims rather than the foregoing description, and all differences within the equivalent scope should be construed as being included in the present invention.

Claims (11)

A pharmaceutical composition for preventing or treating glioblastoma, comprising a cantharidin compound or a pharmaceutically acceptable salt thereof as an active ingredient. According to paragraph 1,
The cantharidin compound is a pharmaceutical composition for preventing or treating glioblastoma, characterized in that it has the ability to selectively inhibit the activity of Anoctamin 1 (ANO1). According to paragraph 1,
The cantharidin compound is a pharmaceutical composition for the prevention or treatment of glioblastoma, characterized in that it has the activity of inhibiting cell proliferation, cell migration, or cell metastasis of glioblastoma. According to paragraph 1,
A pharmaceutical composition for preventing or treating glioblastoma, characterized in that the glioblastoma expresses anogen. An inhibitor of anogen activity, a calcium-dependent chloride ion channel, containing a cantharidin compound as an active ingredient. According to clause 5,
The cantharidin compound is an inhibitor of the activity of an anogen, a calcium-dependent chloride ion channel, characterized in that it inhibits the activity of the anogen in glioblastoma expressing anoctamin 1 (ANO1). Comprising the step of treating a cancer cell line expressing Anoctamin 1 (ANO1) with a cantharidin compound,
Method for inhibiting the activity of anogen in vitro. In clause 7,
A method for inhibiting the activity of anogen in vitro, characterized in that the cancer is glioblastoma. A health functional food for preventing or improving glioblastoma, comprising a cantharidin compound or a salt thereof as an active ingredient. According to clause 9,
The cantharidin compound is a health functional food for preventing or improving glioblastoma, characterized in that it has the ability to inhibit anogen-selective activity. According to clause 9,
The cantharidin compound is a health functional food for preventing or improving glioblastoma, characterized in that it has the activity of inhibiting cell proliferation, inhibiting cell migration, or inhibiting cell metastasis.