KR20180099256A - A composition comprising fucoidan for treating or preventing oral cavity cancer - Google Patents
A composition comprising fucoidan for treating or preventing oral cavity cancer Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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Abstract
Description
본 발명은 푸코이단을 유효성분으로 함유하는 구강암의 예방, 개선 또는 치료를 위한 조성물에 관한 것이다.The present invention relates to a composition for preventing, ameliorating or treating oral cancer containing fucoidan as an active ingredient.
특히, 구강암 세포 (KB cell) 1x106 cells/ml 기준으로, 푸코이단은 0.125 ~ 2 mg/ml인 것을 기술적 특징으로 하고 있다.In particular, it has a technical characteristic that it is 0.125 ~ 2 mg / ml on the basis of 1 × 10 6 cells / ml of oral cancer cells (KB cells).
본 발명에 따른 조성물은 KB cell를 사멸시키는 효능, KB cell의 캐스페이즈(caspase) -3, -8 및 -9의 발현을 촉진하는 효능, KB cell의 분절 PARP의 발현을 촉진하는 효능, KB cell의 주기가 세포자멸(apoptosis)기로 진행되는 것을 유도하는 효능, KB cell의 Bcl-2의 발현을 저해하는 효능, KB cell의 Bad, Bim 및 Bax를 포함하는 프로-아포토시스(pro-apoptosis) 단백질의 발현을 촉진하는 효능과 ERK, pERK, JNK, pJNK, p38 및 pp38을 포함하는 MAPK 통로 단백질의 발현을 촉진하는 효능을 보유하고 있다.The composition according to the present invention is effective in killing KB cells, promoting the expression of caspase-3, -8 and -9 of KB cells, promoting the expression of PARP in KB cells, Apoptosis proteins including Bad, Bim, and Bax of KB cells, the effect of inhibiting the expression of Bcl-2 in KB cells, the effect of inducing the cycle of apoptosis And has an effect of promoting expression and promoting the expression of MAPK channel protein including ERK, pERK, JNK, pJNK, p38 and pp38.
구강암(oral cavity cancer)이란 구강에 생긴 암 세포로 이루어진 종괴이다. 악성 종양의 종류로는 편평상피세포암, 소타액선암, 육종, 림프종 및 흑색종 등을 들 수 있다.Oral cavity cancer is a mass composed of cancerous cells in the oral cavity. Types of malignant tumors include squamous cell carcinoma, small salivary gland carcinoma, sarcoma, lymphoma and melanoma.
구강암은 환경학적 요인(흡연, 음주, 동물성 지방 및 포화지방의 과다 섭취 등), 영양학적 요인(비타민, 아연, 구리 또는 철 결핍증 등) 및 병리학적 요인(바이러스 감염 등) 등 다양한 요인에 의하여 발병하는 것으로 알려져 있다.Oral cancer is caused by various factors such as environmental factors (smoking, drinking, excessive intake of animal fat and saturated fats), nutritional factors (such as vitamin, zinc, copper or iron deficiency) and pathological factors .
구강암은 조기발견이 가능함에도 불구하고 5년 생존율이 30%에 불과하며, 혀에 발생할 경우 더욱 예후가 좋지 않다.Despite early detection of oral cancer, the 5-year survival rate is only 30%, and the prognosis is worse when it occurs in the tongue.
구강암의 치료에는 병소를 냉동 요법 등의 수술적 치료, 방사선 요법 및 화학 요법 등의 비수술적 치료가 수행되고 있으나, 모든 치료 요법에 부작용이 따르는 실정이다.In the treatment of oral cancer, non-surgical treatment such as cryotherapy such as cryotherapy, radiotherapy and chemotherapy is performed, but all therapies have side effects.
냉동 요법은 부종, 수포, 진물, 가피, 동통, 감염 및 출혈 등의 부작용이 있고, 심할 경우 복원을 위한 성형이 필요할 정도로 조직이 괴사될 수 있으며, 방사선 요법은 홍반, 색소침착, 건조성 또는 습윤성 피부박리 및 모세혈관 확장증 등의 부작용이 있다.Cryotherapy has side effects such as edema, blisters, sore throat, scarring, pain, infection and hemorrhage. In severe cases, the tissue may be necrotic enough to require reconstitution. Radiotherapy may include erythema, pigmentation, Skin exfoliation and capillary vasodilation.
더불어 화학 요법은 구역, 구토, 구내염, 설사 및 골수기능장애 등의 부작용이 있다.In addition, chemotherapy has side effects such as nausea, vomiting, stomatitis, diarrhea, and bone marrow dysfunction.
이에 본 출원인은 부작용이 없으며, 구강암의 세포주인 KB cell을 표적으로 함으로써 구강암을 예방, 개선 또는 치료할 수 있는 조성물을 제공할 수 있다고 판단하여, 푸코이단을 유효성분으로 함유하는 구강암 저해 조성물을 안출하였다.Accordingly, the applicant of the present invention has determined that it is possible to provide a composition capable of preventing, ameliorating, or treating oral cancer by targeting KB cell, which is a cell line of oral cancer, and has found a oral cancer inhibitory composition containing fucoidan as an active ingredient.
이하에서, 본 발명의 유효성분인 푸코이단에 대하여 간략히 서술하도록 하겠다.Hereinafter, the fucoidan as an active ingredient of the present invention will be briefly described.
푸코이단(fucoidan)은 끈적끈적한 점질 구조의 황산염화한 다당류로 고미역, 다시마 등 갈조류에 들어있는 성분이다. Fucoidan (fucoidan) is a sticky, viscous, sulphated polysaccharide that is contained in brown algae such as goat, seaweed, and kelp.
푸코이단은 갈조류에 유연성을 부여하여 격렬한 조수의 흐름으로부터 해조류가 보호될 수 있도록 한다. 갈조류로부터 추출된 푸코이단은 평균 분자량 20kDa이며, 후코스(Fucose)라는 기본당과 황산기가 결합되어 있다. 황산화푸코이단에서 생기는 F-푸코이단과 20% 정도의 글루쿠론산를 포함한 U-푸코이단 두 종류가 있다.Fucoidan imparts flexibility to brown algae so that algae can be protected from intense tidal currents. The fucoidan extracted from brown algae has an average molecular weight of 20 kDa and is bound to a basic sugar and a sulfate group called fucose. There are two types of Fucoidan, Fucoidan from Fucoidan sulfate and U-Fucoidan, which contains about 20% glucuronic acid.
푸코이단은 기능성 식품의 기초원료, 식이보조제, 첨가제 등으로 사용되고 있으며, 콜레스테롤의 배설을 도와 혈중 콜레스테롤 수치를 낮추고 혈관 질환을 예방하며 비만이 성인병으로 발병되는 것을 예방시켜 준다.Fucoidan is used as a basic ingredient of functional foods, dietary supplements, additives, etc. It helps to excrete cholesterol, lowering blood cholesterol level, preventing blood vessel disease and preventing obesity from becoming an adult disease.
또한, 최근 연구에서는 푸코이단이 혈액응고방지작용, 항종양작용, 위궤양 치료 촉진작용, 항균작용, 혈압상승억제작용, 간세포증식인자(HGF)생산유도, 혈당상승억제작용, 면역세포조절작용, 항알레르기작용, 항바이러스작용이 있다고 하였다. In recent studies, fucoidan has been shown to inhibit blood coagulation, antitumor action, gastric ulcer treatment promoting action, antimicrobial action, inhibition of blood pressure increase, production of hepatocyte growth factor (HGF), inhibition of hyperglycemia, Action, and antiviral activity.
특히 소화기계통 암 종류 치유에 뛰어난 효과가 있는 것으로 보고된 바 있으며, 대부분의 암 치유에도 매우 우수한 효과가 있는 것으로 나타났다. F-푸코이단은 임파종 세포줄기의 자살을 유도하며 토끼에서는 이상증식을 억제할 수 있다는 보고가 있었다.Especially, it has been reported that it has excellent effect on the healing of digestive system cancer type, and it has been shown that it has a very excellent effect on most cancer healing. F-fucoidan has been reported to induce suicide of lymphoid stem cells and to suppress abnormal proliferation in rabbits.
한편 본 발명과 관련된 선행특허를 살펴보면, 대한민국 등록특허공보 제10-1144493호에 저분자의 알지네이트, 푸코이단 또는 은-알지네이트를 유효성분으로 함유하는 항균 화장료 조성물이 기재되어 있다. In the prior art related to the present invention, Korean Patent Registration No. 10-1144493 discloses an antibacterial cosmetic composition containing low-molecular alginate, fucoidan or silver-alginate as an active ingredient.
그러나 선행특허는 스타피로코커스 아우레우스(Staphylococcus aureus)에 대한 기재만 있을 뿐, 구강암에 대한 효능이 있는지 여부는 알 수 없으며, 이에 대한 착안점이나 시사점도 기재된바 없다.However, the prior patent has only a description of Staphylococcus aureus , and it is not known whether or not it has efficacy against oral cancer, and there is no description or suggestion about it.
본 발명의 목적은 구강암의 세포주인 KB cell의 세포자멸사를 다각적으로 유도함으로써, 구강암을 근본적으로 예방, 개선 또는 치료할 수 있는 조성물을 제공하는 것이다.It is an object of the present invention to provide a composition capable of fundamentally preventing, ameliorating or treating oral cancer by inducing apoptosis of KB cell which is a cell line of oral cancer in various ways.
본 발명의 목적은 푸코이단을 유효성분으로 함유하는 구강암의 예방, 개선 또는 치료를 위한 조성물을 제공하는 것이다.It is an object of the present invention to provide a composition for prevention, improvement or treatment of oral cancer containing fucoidan as an active ingredient.
본 발명은, 푸코이단을 유효성분으로 함유하는 구강암의 예방, 개선 또는 치료를 위한 약학적 조성물을 제공함으로써, 기술적 과제를 해결하고자 한다.The present invention aims at solving the technical problem by providing a pharmaceutical composition for prevention, improvement or treatment of oral cancer containing fucoidan as an active ingredient.
특히, 상기 조성물에 함유되는 푸코이단의 농도는 구강암 세포 KB cell 1x106 cells/ml 기준으로 0.125 ~ 2 mg/ml인 것을 특징으로 한다.In particular, the concentration of fucoidan contained in the composition is 0.125 to 2 mg / ml based on 1 × 10 6 cells / ml of oral cancer cell KB cells.
또한, 상기 조성물은 KB cell를 사멸시키는 효능, KB cell의 캐스페이즈(caspase) -3, -8 및 -9의 발현을 촉진하는 효능, KB cell의 분절 PARP의 발현을 촉진하는 효능, KB cell의 주기가 세포자멸(apoptosis)기로 진행되는 것을 유도하는 효능, KB cell의 Bcl-2의 발현을 저해하는 효능, KB cell의 프로-아포토시스(pro-apoptosis) 단백질의 발현을 촉진하는 효능 및 KB cell의 MAPK 통로 단백질의 발현을 촉진하는 효능을 보유하는 것을 특징으로 한다.In addition, the composition has an effect of killing KB cells, an effect of promoting the expression of caspase-3, -8 and -9 of KB cells, an effect of promoting the expression of PARP of KB cells, The effect of inducing the cycle to progress to apoptosis, the effect of inhibiting the expression of Bcl-2 of KB cell, the effect of promoting the expression of pro-apoptosis protein of KB cell, And has an effect of promoting the expression of MAPK channel protein.
본 발명은, 푸코이단을 유효성분으로 함유하는 구강암의 예방 또는 개선을 위한 건강기능식품 조성물을 제공함으로써, 기술적 과제를 해결하고자 한다.The present invention aims to solve the technical problem by providing a health functional food composition for preventing or ameliorating oral cancer containing fucoidan as an active ingredient.
본 발명에 따른 푸코이단을 유효성분으로 함유하는 구강암의 예방, 개선 또는 치료를 위한 조성물은 KB cell를 사멸시키는 효능, KB cell의 캐스페이즈 -3, -8 및 -9의 발현을 촉진하는 효능, KB cell의 분절 PARP의 발현을 촉진하는 효능 및 KB cell의 주기가 세포자멸기로 진행되는 것을 유도하는 효능을 보유하고 있다.The composition for preventing, ameliorating or treating oral cancer containing fucoidan as an active ingredient according to the present invention is useful for killing KB cells, promoting the expression of caspase-3, -8 and -9 of KB cells, KB cell PARP expression and the ability to induce KB cell cycle progression to apoptosis.
본 발명에 따른 푸코이단을 유효성분으로 함유하는 구강암의 예방, 개선 또는 치료를 위한 조성물은 KB cell의 Bcl-2의 발현을 저해하는 효능, KB cell의 프로-아포토시스 단백질의 발현을 촉진하는 효능 및 KB cell의 MAPK 통로 단백질의 발현을 촉진하는 효능을 보유하고 있다.The composition for preventing, ameliorating or treating oral cancer containing fucoidan as an active ingredient according to the present invention is effective for inhibiting the expression of Bcl-2 in KB cell, the effect for promoting expression of pro-apoptotic protein in KB cell, cell MAPK pathway protein.
도 1은 구강암 세포에 대한 푸코이단의 세포독성 실험 결과를 나타낸 그래프이다.
도 2는 푸코이단이 구강암 세포를 세포사멸시킬 때의 핵의 형태를 관찰한 결과를 나타낸 사진이다.
도 3a 및 도 3b는 구강암 세포에 대해 푸코이단이 세포주기를 변화시키는 것을 분석한 결과를 나타낸 그래프이다.
도 4는 푸코이단이 구강암 세포을 세포사멸시킬 때의 세포 형태를 관찰한 결과를 나타낸 그래프이다.
도 5a 및 도 5b는 푸코이단이 구강암 세포의 세포사멸 관련 효소들의 발현 양상에 미치는 영향을 분석한 결과를 나타낸 그래프이다.
도 6a 및 도 6b는 푸코이단이 구강암 세포의 미토콘드리아 신호 전달 관련 단백질의 발현 양상에 미치는 영향을 분석한 결과를 나타낸 그래프이다. 1 is a graph showing the cytotoxicity test results of fucoidan against oral cancer cells.
FIG. 2 is a photograph showing the result of observing the morphology of the nucleus when fucoidan cells kill the oral cancer cells.
FIGS. 3A and 3B are graphs showing the results of analysis of changes in cell cycle of fucoidan against oral cancer cells. FIG.
FIG. 4 is a graph showing the results of observing cell morphology when fucoidan cells kill oral cancer cells.
5A and 5B are graphs showing the results of analysis of the effect of fucoidan on the expression pattern of apoptosis-related enzymes of oral cancer cells.
FIGS. 6A and 6B are graphs showing the results of analysis of the effect of fucoidan on the expression pattern of mitochondrial signal transduction related proteins in oral cancer cells. FIG.
본 명세서 및 청구 범위에 사용된 용어나 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 안 되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다.The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.
따라서 본 명세서에 기재된 실시예, 참조예 및 도면에 기술된 사항은 본 발명의 가장 바람직한 일 예에 불과할 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다. Therefore, the embodiments described in the present specification, the reference examples, and the drawings are merely the most preferred examples of the present invention, and not all of the technical ideas of the present invention are described. Therefore, It should be understood that various equivalents and modifications may be present.
실시예Example 1. One. 푸코이단을Fucoidan 유효성분으로 함유하는, 구강암을 예방, 개선 또는 Prevention or amelioration of oral cancer, as an active ingredient, or 치Tooth 료하기 위한 조성물Composition
푸코이단을 유효성분으로 함유하는, 구강암을 예방, 개선 또는 치료하기 위한 약학적 조성물 또는 식품 조성물을 제조한다.A pharmaceutical composition or a food composition for preventing, ameliorating or treating oral cancer is prepared, which contains fucoidan as an active ingredient.
푸코이단은 미역, 다시마 등과 같은 갈조류(brown seaweeds)의 줄기 또는 뿌리를 물, 에탄올 또는 메탄올 또는 기타 유기용매를 이용하여 추출 또는 분획추출한 후에 분리 동정한다. 추출용매의 종류에 따라 추출 온도, 추출 시간, 용매의 양 및 잔류성분 처리 방식 등을 달리하여 처리한다.Fucoidan is extracted and fractionated by extraction with water, ethanol, methanol or other organic solvent, and then separated and identified. Depending on the type of extraction solvent, the extraction temperature, the extraction time, the amount of solvent, and the method of treating the residual components are treated differently.
분리 동정된 푸코이단의 농도는 0.125 ~ 2 mg/ml에 해당하도록 농축하여 사용할 수 있다. 이는 하기 실험예들의 데이터에 근거한다.The concentration of the fucoidan to be separated and isolated may be used in a concentration of 0.125 to 2 mg / ml. This is based on the data of the following experimental examples.
푸코이단 이외의 약제학적으로 허용된 첨가제나 식품학적으로 허용된 첨가제를 이용하여 사용목적에 맞게 조성물을 제조한다.The composition is prepared for the intended use by using a pharmaceutically acceptable additive other than fucoidan or a pharmaceutically acceptable additive.
실험예Experimental Example 1. 구강암 세포에 대한 1. For oral cancer cells 푸코이단의Fucoidan 세포독성 실험 Cytotoxicity experiment
(1) 실험준비(1) Preparing the experiment
구강암세포 (KB cell)는 1x105 cells 농도로 24-well 플레이트에서 배양되었으며, 푸코이단(fucoidan)을 농도별로 처리한 후 24시간 배양하였다. 그 후 MTT 방법을 통해 세포독성을 확인하였다. MTT 분석은 통상적인 방법을 채용하였다.The oral cancer cells (KB cells) were cultured in a 24-well plate at a concentration of 1 × 10 5 cells, and fucoidan was treated at different concentrations and cultured for 24 hours. After that, cytotoxicity was confirmed by MTT method. The MTT analysis employed a conventional method.
(2) 실험결과(2) Experimental results
도 1은 구강암 세포에 대한 푸코이단의 세포독성 실험 결과를 나타낸 그래프이다.1 is a graph showing the cytotoxicity test results of fucoidan against oral cancer cells.
실험결과, 0.25 mg/mL 농도까지는 독성을 나타내지 않았으며, 1 mg/mL 농도에서 50%이상의 세포억제를 보였다.As a result, it was not toxic up to the concentration of 0.25 mg / mL and showed cell inhibition of more than 50% at the concentration of 1 mg / mL.
실험예Experimental Example 2. 세포사멸시 핵의 형태 분석 실험 2. Experiments on the morphology of nuclei in cell death
(1) 실험준비(1) Preparing the experiment
구강암세포 (KB cell)(1x105 cells/ml)에 푸코이단을 농도별로 처리한 후 24시간 배양하였다. 그 후 Hoechst 33342 염색을 한 후 NICON Ti-U 카메라가 설치된 반전 형광 현미경으로 관찰하였다.Fucoidan was administered to oral cancer cells (1 × 10 5 cells / ml) at different concentrations and cultured for 24 hours. After staining with Hoechst 33342, it was observed with an inverted fluorescence microscope equipped with a NICON Ti-U camera.
(2) 실험결과(2) Experimental results
도 2는 푸코이단이 구강암 세포를 세포사멸시킬 때의 핵의 형태를 관찰한 결과를 나타낸 사진이다.FIG. 2 is a photograph showing the result of observing the morphology of the nucleus when fucoidan cells kill the oral cancer cells.
핵붕괴를 관찰한 결과, 농도의존적으로 세포사멸시 핵의 붕괴가 이루어짐을 알 수 있다.As a result of observing the nuclear decay, it can be understood that the nucleus collapses upon cell death in a concentration dependent manner.
실험예Experimental Example 3. 세포주기 변화 분석 실험 3. Cell cycle change assay
(1) 실험준비(1) Preparing the experiment
세포 주기는 subG1기, G0/G1기, S기 및 G2/M기의 4단계로 분류할 수 있다. The cell cycle can be divided into four stages: subG1, G0 / G1, S, and G2 / M.
그 중 subG1기는 자멸이 진행되는 세포에서만 발견되는 시기로써, 특정 세포의 주기를 상기 subG1기가 되도록 유도하면 특정 세포는 자멸된다. 또한 G2/M기는 분열이 활성화되는 시기이다.Among them, the subG1 group is found only in apoptotic cells. When a certain cell cycle is induced to be the subG1 group, certain cells are self-destructed. Also, the G2 / M group is the period when the cleavage is activated.
푸코이단의 농도를 조정하여 KB cell(1x105 cells/ml)에 처리한 후 24시간 동안 배양하였다.The concentration of fucoidan was adjusted to be treated with KB cells (1 × 10 5 cells / ml) and cultured for 24 hours.
통상적인 방법으로 PI(propidium iodide) 염색을 수행하였다.PI (propidium iodide) staining was performed in a conventional manner.
(2) 실험결과(2) Experimental results
도 3a 및 도 3b는 구강암 세포에 대해 푸코이단이 세포주기를 변화시키는 것을 분석한 결과를 나타낸 그래프이다.FIGS. 3A and 3B are graphs showing the results of analysis of changes in cell cycle of fucoidan against oral cancer cells. FIG.
농도의존적으로 sub-G1기이 증가하였으며 1 mg/mL 농도에서 G2/M기가 증가하는 것을 관찰하였다.The sub-G1 phase increased in a concentration-dependent manner and the G2 / M phase was observed to increase at a concentration of 1 mg / mL.
실험예Experimental Example 4. 세포사멸시 세포 형태 분석 실험 4. Cell morphology assay in cell death
(1) 실험준비(1) Preparing the experiment
상기 실험예 3과 동일하게 준비하였다. 그후 TUNEL (annexin V) 방법으로 형광염색을 한 후 flow cytometry로 세포형태를 관찰하였다.Was prepared in the same manner as in Experimental Example 3. Then, fluorescent staining was performed by TUNEL (annexin V) method and cell morphology was observed by flow cytometry.
(2) 실험결과(2) Experimental results
도 4는 푸코이단이 구강암 세포을 세포사멸시킬 때의 세포 형태를 관찰한 결과를 나타낸 그래프이다.FIG. 4 is a graph showing the results of observing cell morphology when fucoidan cells kill oral cancer cells.
실험결과, 푸코이단의 농도 의존적으로 세포사멸을 증가하는 것을 확인하였다. As a result of the experiment, it was confirmed that the cell death was increased depending on the concentration of fucoidan.
실험예Experimental Example 5. 세포사멸 관련 효소들의 발현 분석 실험 5. Expression analysis of apoptosis-related enzymes
(1) 실험준비(1) Preparing the experiment
구강암세포 (KB cell)(1x106 cells/ml)에 푸코이단을 농도별로 처리한 후 24시간 배양하였다. 그 후 mRNA와 단백질변화를 RT PCR과 웨스턴블럿 방법을 통하여 확인하였다.Fucoidan was administered to oral cancer cells (1 × 10 6 cells / ml) at different concentrations and cultured for 24 hours. After that, mRNA and protein changes were confirmed by RT PCR and Western blot method.
(2) 실험결과(2) Experimental results
도 5a 및 도 5b는 푸코이단이 구강암 세포의 세포사멸 관련 효소들의 발현 양상에 미치는 영향을 분석한 결과를 나타낸 그래프이다.5A and 5B are graphs showing the results of analysis of the effect of fucoidan on the expression pattern of apoptosis-related enzymes of oral cancer cells.
캐스페이즈는 세포자멸을 유도하는 대표적인 효소이고, PARP 효소는 세포자멸을 억제하는 단백질이며, PARP 효소를 분절하여 불활성화하면 세포자멸이 유도된다. Caspase is a typical enzyme that induces apoptosis. PARP enzyme is a protein that inhibits apoptosis. PARP enzyme is inactivated by fragmentation to induce apoptosis.
실험결과, caspases mRNA 양이 농도의존적으로 활성화되는 것을 확인하였다. 또한, Bcl-2 mRNA 양이 감소하는 것을 확인하였다. 단백질 발현 변화에서도 마찬가지로 caspase-3, -8, -9 단백질이 농도의존적으로 활성이 증가하는 것을 확인할 수 있었고, PARP 단백질은 활성형 단백질 (89 Kb)이 증가하는 것을 확인하였다.As a result, it was confirmed that the amount of caspase mRNA was activated in a concentration dependent manner. In addition, it was confirmed that the amount of Bcl-2 mRNA decreased. The expression of caspase-3, -8 and -9 proteins was also increased in a concentration-dependent manner, and that of the PARP protein was increased by 89 Kb.
실험예Experimental Example 6. 미토콘드리아 신호 전달 관련 단백질의 발현 분석 실험 6. Expression analysis of mitochondrial signaling-related proteins
(1) 실험준비(1) Preparing the experiment
구강암세포 (KB cell)(1x106 cells/ml)에 푸코이단을 농도별로 처리한 후 24시간 배양하였다. 그 후 단백질변화를 웨스턴블럿 방법을 통하여 확인하였다.Fucoidan was administered to oral cancer cells (1 × 10 6 cells / ml) at different concentrations and cultured for 24 hours. Protein changes were then confirmed by western blot method.
(2) 실험결과(2) Experimental results
도 6a 및 도 6b는 푸코이단이 구강암 세포의 미토콘드리아 신호 전달 관련 단백질의 발현 양상에 미치는 영향을 분석한 결과를 나타낸 그래프이다. FIGS. 6A and 6B are graphs showing the results of analysis of the effect of fucoidan on the expression pattern of mitochondrial signal transduction related proteins in oral cancer cells. FIG.
Bcl-2는 세포자멸을 저해하는 역할을 하는 단백질이며, Bad, Bax 및 Bim 등의 프로-아포토시스 단백질은 세포자멸을 촉진하는 역할을 한다.Bcl-2 is a protein that inhibits apoptosis, and pro-apoptotic proteins such as Bad, Bax, and Bim play a role in promoting apoptosis.
실험결과, 항세포사멸 관련 단백질인 Bcl-2 발현이 감소하였으며, 이와 반대인 Bax 단백질은 증가하는 것을 확인하였다. As a result, the expression of Bcl-2, an anti-apoptotic protein, and Bax protein, which is the opposite, were increased.
또한, MAPKs 관련 단백질의 인산화를 관찰한 결과, ERK의 인산화가 감소되는 것을 확인하였다. ERK, pERK, JNK, pJNK, p38 및 pp38을 포함하는 MAPK 통로 단백질은 세포자멸을 유도하는 역할을 한다.In addition, the phosphorylation of MAPKs-related proteins was observed, indicating that ERK phosphorylation was reduced. MAPK pathway proteins including ERK, pERK, JNK, pJNK, p38 and pp38 play a role in inducing apoptosis.
Claims (5)
A pharmaceutical composition for preventing, improving or treating oral cancer containing fucoidan as an active ingredient.
상기 조성물에 함유되는 푸코이단의 농도는 구강암 세포 KB cell 1x106 cells/ml 기준으로 0.125 ~ 2 mg/ml인 것을 특징으로 하는, 구강암의 예방, 개선 또는 치료를 위한 약학적 조성물.
The method according to claim 1,
A pharmaceutical composition for preventing, ameliorating or treating oral cancer, wherein the concentration of fucoidan contained in the composition is 0.125 to 2 mg / ml based on 1 × 10 6 cells / ml of oral cancer cell KB cells.
상기 조성물은 KB cell를 사멸시키는 효능, KB cell의 캐스페이즈(caspase) -3, -8 및 -9의 발현을 촉진하는 효능, KB cell의 분절 PARP의 발현을 촉진하는 효능, KB cell의 주기가 세포자멸(apoptosis)기로 진행되는 것을 유도하는 효능, KB cell의 Bcl-2의 발현을 저해하는 효능, KB cell의 프로-아포토시스(pro-apoptosis) 단백질의 발현을 촉진하는 효능 및 KB cell의 MAPK 통로 단백질의 발현을 촉진하는 효능을 보유하는 것을 특징으로 하는, 구강암의 예방, 개선 또는 치료를 위한 약학적 조성물.
The method according to claim 1 or 2,
The composition is effective in killing KB cells, promoting the expression of caspase-3, -8 and -9 of KB cells, promoting the expression of PARP in KB cells, The effect of inhibiting the expression of Bcl-2 of KB cell, the effect of promoting the expression of pro-apoptosis protein of KB cell, and the effect of promoting progression to apoptosis of KB cell, A pharmaceutical composition for preventing, ameliorating or treating oral cancer, which has an effect of promoting expression of a protein.
A pharmaceutical preparation for preventing, ameliorating or treating oral cancer, to which a pharmaceutical additive is added to the composition according to any one of claims 1 to 3.
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| KR101144493B1 (en) | 2009-11-27 | 2012-05-11 | 조선대학교산학협력단 | Antibiotic cosmetic composition comprising alginate, fucoidan or silver-alginate having low molecular weight |
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Non-Patent Citations (2)
| Title |
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| Kim DW, Chi YS, Son KH, Chang HW, Kim JS, Kang SS, Kim HP, Effects of fucoidane G, a prenylated flavonoid from Sophora flavescens, on cyclooxygenase-2 and in vivo inflammatory response, Archives of pharmacal research, 2002, v.25, no.3, pp.329-335 |
| Wun ZY, Lin CF, Huang WC, Huang YL, Xu PY, Chang WT, Wu SJ, Liou CJ, Anti-inflammatory effect of fucoidane G isolated from Sophora flavescens in lipopolysaccharide-stimulated mouse macrophages, Food and chemical toxicology, 2013, v.62, pp. 255-261 |
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