JP2001151676A - Apoptosis inducing agent and cancer-treating agent and food using apoptosis inducing potency - Google Patents

Abstract

PROBLEM TO BE SOLVED: To enable the use of an apoptosis inducing agent having high safety as a cancer-treating drug or a carcinogenesis preventing food. SOLUTION: The apoptosis inducing agent contains sesamine and/or episesamine and/or sesamol as active components. The cancer treating agent and food are produced taking advantage of the apoptosis inducing potency of the above components.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an apoptosis-inducing agent for inducing apoptosis, which is one type of cell death,
In addition, the present invention relates to a medicine, a cancer treatment drug and a food utilizing the ability to induce apoptosis.

[0002]

2. Description of the Related Art Cancer is currently the leading cause of death,
People are very concerned about its prevention. In addition, many methods for preventing cancer that can be taken on a daily basis have been proposed.

In recent years, in the field of cancer research, studies on apoptosis, that is, the self-destruction of cancer cells, have become active.
Apoptosis plays an important role in the formation of tissues and organs in biological ontogenesis, as well as in maintaining and protecting the homeostasis of ecology. In addition, it is being elucidated that there is a deep connection with the occurrence of many diseases.

[0004] Abnormal control action by cell apoptosis is considered to be one of the causes in cancer formation. It is said that if cells that should be killed survive without undergoing apoptosis, that is, self-destruction of the cells, the cells will receive various stimuli and accumulate mutations on the chromosome, eventually becoming cancer cells. Cancer cells can only proliferate after acquiring the resistance mechanism of apoptosis. In other words, canceration of cells with various gene mutations is related to the acquisition of resistance to apoptosis.

[0005]

Accordingly, an object of the present invention is to provide a novel safe apoptosis inducer.

[0006]

The present inventors have found that sesamin, episesamin and sesamol isolated or synthesized from sesame seeds, sesame meal, sesame oil and by-products of sesame oil production have a remarkable apoptosis-inducing effect on cancer cells. The inventors have found that the present invention has been completed.

That is, the present invention provides an apoptosis inducer containing sesamin and / or episesamin and / or sesamol as an active ingredient.

The present invention also provides a therapeutic agent for cancer utilizing the apoptosis-inducing ability of sesamin and / or episesamin and / or sesamol.

Further, the present invention provides a food utilizing the apoptosis-inducing ability of sesamin and / or episesamin and / or sesamol.

[0010] The "food" of the present invention refers to a beverage or a solid food, preferably a food having a specific health effect, or a food prepared by utilizing the function of a bioregulatory component.
Means functional food.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION Sesamin, episesamin and sesamol used in the present invention can be used alone or as a mixture. These compounds include sesame seeds,
It can be isolated by a known method from sesame meal, sesame oil, and by-products of sesame oil production. For example, it can be obtained by extracting from sesame oil with an organic solvent and purifying it by column chromatography. Examples of the organic solvent used for the extraction include alcohols such as methanol and ethanol, methylene chloride, ethyl acetate, and acetone. The method of isolation is not limited to this method.

In addition, the extraction raw material is not limited to the above-mentioned sesame, but spices, quince, Kiriki, etc. known as plants containing these compounds can also be used.

These compounds can be obtained not only by extraction from natural products but also by synthesis.

In the present invention, generally, as an apoptosis-inducing agent, sesamin, episesamin, or sesamol alone or as a mixture is orally administered,
Alternatively, it is desirable to administer as an oral preparation by mixing with an excipient or carrier. It may be administered as a parenteral.

When administered as an oral preparation, it can be formulated into tablets, capsules, granules, fine granules and the like. In this case, the preparation can be made by using a sweetener, a lubricant and a flavoring agent as appropriate.

When administered as a parenteral preparation, injections, suppositories, and the like in the form of a solution with water or another pharmaceutically acceptable liquid, or a dispersion, suspension, stabilizer or the like are added. Agent and the like.

[0017] The type and composition of the therapeutic agent for cancer of the present invention comprising sesamin and / or episesamin and / or sesamol as an active ingredient, as described above, depends on the route and method of administration, as long as it is pharmaceutically acceptable. It is provided in an appropriately modified mode.

The dosage varies depending on the purpose of administration and the subject of administration.
３０30 mg / day, 1-5 mg / day for parenteral administration.

When the compound of the present invention is used as a food,
Although it may be in the form of a preparation, it can be processed and produced by a general production method by adding a required amount of the compound of the present invention to a food material.

For example, sesamin and / or episesamin and / or sesamol of the present invention may be added directly to beverages as an additive or added to solid foods such as biscuits to prevent cancer, health foods or functional foods. Etc. can also be provided.

The sesamin and / or episesamin and / or sesamol of the present invention can be dissolved in, for example, fats and oils, ethanol, propylene glycol, glycerin or a mixture thereof and added to a beverage as a liquid or to a solid food. It is possible. Or, if necessary, mixed with a binder such as gum arabic, dextrin,
It can be in the form of powder or granules and added to beverages or solid foods.

The type of food to which the compound of the present invention is added is not particularly limited. Furthermore, in foods containing the compound of the present invention, sesamin and / or episesamin and / or
Although there is no particular limitation on the amount of sesamol used, intake as a health food or a functional food is used for disease prevention and health maintenance. Therefore, sesamin and / or
Or episesamin and / or sesamol in a total of 1 to 20
% By weight is preferred.

The compound which is the active ingredient of the present invention is a compound which has been conventionally found in foods, and is clearly superior in terms of safety. Also, Japanese Patent Application Laid-Open No. 05-5138
No. 8 has been confirmed to be safe.

[0024]

EXAMPLES Example 1 Inhibitory Activity of Sesamin, Episesamin and Sesamol on Human Leukemia Cells Human leukemia cells were cultured in RPMI1640 medium containing 10% fetal calf serum. Ethanol (control group), an ethanol solution of sesamin, episesamin, and sesamol (experimental group) were added to human leukemia cells adjusted to 5 × 10 ⁵ cells / ml. These were cultured under the conditions of 37 ° C. and 95% air-5% CO ₂ for 3 days, the number of cells was counted, and a cell growth curve was drawn. As shown in Table 1, all the samples in the experimental group exhibited a cell growth inhibitory effect.

[0025]

[Table 1]

Example 2 Apoptosis-Inducing Effect of Sesamin, Episesamin and Sesamol on Human Leukemia Cells Human leukemia cells were cultured in RPMI1640 medium containing 10% fetal bovine serum. Ethanol (control group), an ethanol solution of sesamin, episesamin, and sesamol (experimental group) were added to human leukemia cells adjusted to 5 × 10 ⁵ cells / ml. These were cultured under conditions of 37 ° C. and 95% air-5% CO ₂ for 3 days, and the cells were collected by centrifugation. The nuclei of the collected cells were stained, and the morphology was observed with a fluorescence microscope. FIG.
As a result, apoptotic bodies characteristic of apoptosis induction were observed in all experimental groups.

Example 3 Human leukemia cells were cultured in RPMI 1640 medium containing 10% fetal calf serum. Ethanol (control group), an ethanol solution of sesamin, episesamin, and sesamol (experimental group) were added to human leukemia cells adjusted to 5 × 10 ⁵ cells / ml. These were cultured under conditions of 37 ° C. and 95% air-5% CO ₂ for 3 days, centrifuged to remove the supernatant, and the cells were washed with PBS.
Washed with (-). Add lysis buffer to the cell pellet,
The cells were suspended. Add RNase to the mixture at 50 ° C for 2.5
After reacting for an hour, add protease K solution,
For 2.5 hours. The DNA fragment was extracted, the DNA extract and the gel loading solution were mixed, added to a well of a 2% agarose gel plate, and electrophoresed at 100V. The gel was immersed in water, and DNA that emitted ethidium bromide fluorescence was detected with a UV transilluminator. As shown in FIGS. 2 and 3, it was recognized that DNA fragmentation occurred in all the experimental groups.

[0028]

According to the results of the examples, a highly safe apoptosis inducer containing sesamin and / or episesamin and / or sesamol as an active ingredient is provided. This apoptosis inducer can also be used as a cancer therapeutic. Further, according to the present invention, a food suitable for preventing cancer can be obtained.

[Brief description of the drawings]

FIG. 1 is a schematic diagram of a fluorescence micrograph showing a change in morphology of human leukemia cells of sesamin, episesamin and sesamol in Example 2.

FIG. 2 is a schematic diagram of an electrophoresis photograph showing a distribution state of DNA fragmented by sesamin and episesamin of Example 3.

FIG. 3 shows DNA fragmented by sesamol of Example 3.
FIG. 3 is a schematic diagram of an electrophoresis photograph showing a distribution state of the particles.

[Explanation of symbols]

Fig. 1 A non-added group B 90 micromol / l sesamin added group C 90 micromol / l episesamin added group D 360 micromol / l sesamol added group Fig. 2 M molecular weight marker non-added group (2 days after culture) 90 Micromol / liter sesamin added group (after 2 days of culture) 90 micromol / liter sesamin added group (after 3 days of culture) 90 micromol / liter episesamin added group (after 2 days of culture) 90 micromol / liter episesamin added group (After 3 days of culture) FIG. 3 No addition group of M molecular weight marker (after 2 days of culture) No addition group (after 3 days of culture) 360 μmol / liter sesamol addition group (2 days after culture) 360 μmol / liter sesamol addition group ( 3 days after culture)

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 493/04 101 C07D 493/04 101C F term (Reference) 4B018 MD07 MD56 ME08 MF01 4C022 EA02 4C071 AA01 BB01 CC12 DD05 EE04 FF14 GG02 JJ06 LL01 4C086 AA01 AA02 BA13 CA01 GA02 MA01 MA03 MA04 NA14 ZB26

Claims (3)

[Claims] 1. Sesamin and / or episesamin and / or
Or an apoptosis inducer containing sesamol as an active ingredient 2. Sesamin and / or episesamin and / or
Or a therapeutic agent for cancer utilizing the apoptosis-inducing ability of sesamol 3. Sesamin and / or episesamin and / or
Or a food utilizing the apoptosis-inducing ability of sesamol