KR101941368B1 - Composition for preventing or treating cancer comprising Salvia militiorrhiza - Google Patents
Composition for preventing or treating cancer comprising Salvia militiorrhiza Download PDFInfo
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- KR101941368B1 KR101941368B1 KR1020170078332A KR20170078332A KR101941368B1 KR 101941368 B1 KR101941368 B1 KR 101941368B1 KR 1020170078332 A KR1020170078332 A KR 1020170078332A KR 20170078332 A KR20170078332 A KR 20170078332A KR 101941368 B1 KR101941368 B1 KR 101941368B1
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Abstract
본 발명은 단삼 추출물을 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물에 관한 것으로서, 구체적으로 단삼 추출물은 cleaved-PARP 및 CHOP의 발현량을 증가시켜 세포 내의 활성 산소의 생성량을 증가시키고, 이에 따라 ER-스트레스에 의한 세포사멸이 유도됨으로써, 암의 예방 또는 치료에 유용하게 사용될 수 있다. The present invention relates to a pharmaceutical composition for preventing or treating cancer comprising the extract of Radix Salviae Radix as an active ingredient. Specifically, the extract of Radix Salviae Radix extract increases the amount of cleaved-PARP and CHOP expressed to increase the amount of active oxygen in the cell, Induced ER-stress-induced apoptosis, and thus can be usefully used for prevention or treatment of cancer.
Description
본 발명은 단삼 추출물을 유효성분으로 포함하는 암의 예방 또는 치료용 조성물에 관한 것이다. The present invention relates to a composition for preventing or treating cancer, comprising an extract of Panax ginseng as an active ingredient.
현재, 암의 치료를 위해서는 수술 요법, 방사선 치료 요법 및 화학요법 등이 사용되고 있다. 이 중에서, 화학요법은 항암제를 이용하여 암을 치료하는 방법을 말한다. 오늘날에는 약 60여종의 다양한 항암제가 사용되고 있으며, 최근 암 발생 및 암 세포의 특성에 관한 지식이 많이 알려짐에 따라, 새로운 항암제 개발에 관한 연구가 활발하게 진행되고 있다. 항암 화학치료에 있어 많은 환자들은 항암제의 부작용에 의하여 고통을 받고 있으며, 특히 항암제의 독성으로 인하여 제한적인 투여가 이루어지고 있다. 임상에서 사용되고 있는 항암물질은 암세포뿐만 아니라 정상세포에도 영향을 미치며 투여회수가 반복되면서 치료에 실패하는 등 부작용 및 항암제 내성과 같은 문제점을 가지고 있다. 암 자체의 다양성 및 발병기전의 다양화로 인해 야기되는 기존항암제의 부작용을 극복할 수 있는 새로운 형태의 항암제 치료물질 연구가 진행되고 있다. Currently, surgery, radiation therapy, and chemotherapy are used to treat cancer. Among them, chemotherapy refers to a method of treating cancer using an anticancer agent. Today, about 60 kinds of various anticancer drugs are used. Recently, as knowledge of cancer development and characteristics of cancer cells is well known, researches on the development of new anticancer drugs are being actively carried out. Many patients in cancer chemotherapy suffer from the side effects of anticancer drugs, especially because of the toxicity of anticancer drugs. The anticancer substances used in clinical use have effects such as side effects and anticancer drug resistance, such as failure to treat the cancer cells as well as normal cells as well as repeated administration. A new type of anticancer drug is being studied to overcome the side effects of existing anticancer drugs caused by the diversity of the cancer itself and the variety of pathogenic mechanisms.
다발성골수종은 형질세포종으로도 알려져 있으며, 단일클론단백질들이 비정상적인 증식으로 하게 되는데, 골수에 암세포들의 침습으로 인해 조혈기능이 억제된다. 다발성골수종 진행의 주요요인으로 M 성분이 혈액응고인자들과의 상호작용으로 혈액응고이상을 유발을 야기하고, M 성분이 글로불린을 형성하게 되면 레이노(Raynaud)현상이나 혈액순환장애, 혈액의 고점도 증상이 나타나는 것으로 알려져 있다. 다발성골수종은 전체 암 발병율의 1%를 차지하고, 암으로 인한 사망률에는 2%를 차지하는 종양으로서, National Cancer Institute’s 2009년과 2013년의 SEER database에 의하면 다발성골수종의 5년 생존율은 48.5%로 발표되었다. Multiple myeloma is also known as plasma cell type, and monoclonal proteins result in abnormal proliferation. Hematopoietic function is inhibited by invasion of cancer cells into the bone marrow. As a major factor in the progression of multiple myeloma, the M component induces blood coagulation abnormality due to interaction with blood coagulation factors, and when the M component forms globulin, Raynaud phenomenon, blood circulation disorder, Is known to occur. Multiple myeloma accounts for 1% of all cancer incidence and 2% of cancer deaths. The National Cancer Institute's 2009 and 2013 SEER databases reported a 5-year survival rate of 48.5% for multiple myeloma.
단삼(Salvia miltiorrhiza)은 활혈거어약의 일종으로서, 혈액순환을 돕고, 어혈을 제거하며 사지관절 동통을 완화시키는 것으로 알려져 있다. Danshen (Salvia miltiorrhiza) is known to help to a kind of bow caveman eoyak, blood circulation, remove eohyeol and ease the limb joint pain.
본 발명의 목적은 단삼(Salvia miltiorrhiza) 추출물을 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물을 제공하는 것이다. An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of cancer, including Danshen (Salvia miltiorrhiza) extract as an active ingredient.
본 발명의 또 다른 목적은 단삼 추출물을 유효성분으로 포함하는 항암보조제 조성물을 제공하는 것이다. It is still another object of the present invention to provide an anticancer adjuvant composition comprising an extract of Panax ginseng as an active ingredient.
본 발명의 또 다른 목적은 단삼 추출물을 유효성분으로 포함하는 암의 예방 또는 개선용 식품 조성물을 제공하는 것이다. It is still another object of the present invention to provide a food composition for preventing or ameliorating cancer, which comprises extracts of Panax ginseng as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 단삼(Salvia miltiorrhiza) 추출물을 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물을 제공한다. In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating cancer, including Danshen (Salvia miltiorrhiza) extract as an active ingredient.
본 발명의 일실시예에 있어서, 상기 추출물은 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 추출한 것일 수 있다. In one embodiment of the present invention, the extract may be extracted with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
본 발명의 일실시예에 있어서, 상기 추출물의 농도는 10 내지 200 ㎍/ml 인 것일 수 있고, 바람직하게는 50 내지 100 ㎍/ml 인 것일 수 있으나, 이에 제한되는 것은 아니다. In one embodiment of the present invention, the concentration of the extract may be 10-200 μg / ml, preferably 50-100 μg / ml, but is not limited thereto.
본 발명의 일실시예에 있어서, 상기 추출물은 암세포의 소포체(endoplasmic reticulum, ER) 스트레스로 인한 세포사멸을 유도하는 것일 수 있다. In one embodiment of the present invention, the extract may induce apoptosis due to endoplasmic reticulum (ER) stress.
본 발명의 일실시예에 있어서, 상기 추출물은 활성 산소(reactive oxygen species, ROS)의 생성량을 증가시키는 것일 수 있다. In one embodiment of the present invention, the extract may increase the amount of reactive oxygen species (ROS) produced.
본 발명의 일실시예에 있어서, 상기 추출물은 cleaved-PARP(Poly ADP ribose polymerase) 및 CHOP(CCAAT/-enhancer-binding protein homologous protein)의 발현량을 증가시키는 것일 수 있다. In one embodiment of the present invention, the extract may increase the expression level of cleaved-PARP (Poly ADP ribose polymerase) and CHOP (CCAAT / -enhancer-binding protein homologous protein).
본 발명의 일실시예에 있어서, 상기 암은 다발성 골수종, 대장암, 유방암, 자궁암, 자궁경부암, 난소암, 전립선암, 뇌종양, 두경부암종, 흑색종, 골수종, 백혈병, 림프종, 위암, 폐암, 췌장암, 비소세포성폐암, 간암, 식도암, 소장암, 항문부근암, 나팔관암종, 자궁내막암종, 질암종, 음문암종, 호지킨병, 방광암, 신장암, 수뇨관암, 신장세포암종, 신장골반암종, 골암, 피부암, 두부암, 경부암, 피부흑색종, 안구내흑색종, 내분비선암, 갑상선암, 부갑상선암, 부신암, 연조직육종, 요도암, 음경암, 중추신경계(central nervous system; CNS) 종양, 1차 CNS 림프종, 척수종양, 뇌간신경교종 및 뇌하수체선종으로 이루어진 그룹에서 선택되는 어느 하나인 것일 수 있다. In one embodiment of the present invention the cancer is selected from the group consisting of multiple myeloma, colorectal cancer, breast cancer, uterine cancer, cervical cancer, ovarian cancer, prostate cancer, brain tumor, head and neck carcinoma, melanoma, myeloma, leukemia, lymphoma, gastric cancer, Pancreatic cancer, kidney cancer, renal cell carcinoma, renal pelvic carcinoma, pancreatic cancer, endometrial carcinoma, endometrial carcinoma, vaginal cancer, vulvar carcinoma, Hodgkin's disease, bladder cancer, kidney cancer, Cancer of the central nervous system (CNS), 1 tumor of the central nervous system (CNS), 1 malignant melanoma, 1 malignant melanoma, 1 malignant melanoma, 1 malignant melanoma, 1 malignant melanoma, 1 malignant melanoma, Primary CNS lymphoma, spinal cord tumor, brainstem glioma, and pituitary adenoma.
또한, 본 발명은 단삼 추출물을 유효성분으로 포함하는 항암보조제 조성물을 제공한다. In addition, the present invention provides an anticancer adjuvant composition comprising an extract of Panax ginseng as an active ingredient.
또한, 본 발명은 단삼 추출물을 유효성분으로 포함하는 암의 예방 또는 개선용 식품 조성물을 제공한다. Further, the present invention provides a food composition for preventing or ameliorating cancer comprising the extract of Panax ginseng as an active ingredient.
본 발명에 따른 단삼 추출물은 cleaved-PARP 및 CHOP의 발현량을 증가시켜 세포 내의 활성 산소의 생성량을 증가시키고, 이에 따라 ER-스트레스에 의한 세포사멸이 유도됨으로써, 암의 예방 또는 치료에 유용하게 사용될 수 있다. The extract of Dansamp according to the present invention increases the expression amount of cleaved-PARP and CHOP to increase the production of active oxygen in the cell and thereby induces apoptosis by ER-stress, thereby being useful for prevention or treatment of cancer .
도 1은 단삼 추출물을 처리한 후, 다발성 골수종 세포주인 U937의 세포 생존율을 확인한 결과를 나타낸 것이다.
도 2는 단삼 추출물을 처리한 후, 다발성 골수종 세포주인 U937에서의 세포사멸 관련 단백질들의 발현 정도를 확인한 결과를 나타낸 것이다.
도 3은 단삼 추출물을 처리한 후, 다발성 골수종 세포주인 U937에서의 ROS 발현 정도를 확인한 결과를 나타낸 것이다.FIG. 1 shows the results of confirming the cell survival rate of U937, a multiple myeloma cell line, after treatment with Radix Salviae Radix extract.
FIG. 2 shows the results of confirming the expression level of apoptosis-related proteins in U937, a multiple myeloma cell line, after treatment with extracts of Panax ginseng.
FIG. 3 shows the results of confirming the degree of ROS expression in U937, a multiple myeloma cell line, after treatment with extracts of Panax ginseng.
본 발명은 단삼(Salvia miltiorrhiza) 추출물을 유효성분으로 포함하는 암의 예방 또는 치료용 약학 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of cancer, including Danshen (Salvia miltiorrhiza) extract as an active ingredient.
본 발명에서 용어, "추출물(extract)"은 생약을 적절한 침출액으로 짜내고 침출액을 증발시켜 농축한 제제를 의미하는 것으로, 이에 제한되지는 않으나, 추출처리에 의해 얻어지는 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 이들의 조정제물 또는 정제물일 수 있다. 상기 단삼 추출물은 통상의 기술 분야에 공지된 일반적인 추출방법, 분리 및 정제방법을 이용하여 제조할 수 있다. 상기 추출방법으로는, 이에 제한되지는 않으나, 바람직하게 열탕 추출, 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 방법을 사용할 수 있다.The term " extract " in the present invention means a preparation which is prepared by squeezing a herbal medicine with an appropriate extract solution and evaporating the extract solution. The extract solution obtained by the extraction treatment, the diluent or concentrate of the extract, Or a dried product obtained by drying the above, a controlled preparation thereof or a purified product thereof. The extract can be prepared by a common extraction method, separation and purification methods known in the art. The extraction method may be, but not limited to, hot water extraction, hot water extraction, cold extraction, reflux cooling extraction, or ultrasonic extraction.
본 발명에서, 추출용매는 물, 유기용매 또는 이들의 혼합용매 등을 사용할 수 있으며, 상기 유기용매는 탄소수 1 내지 4의 알코올이나, 에틸아세테이트 또는 아세톤 등의 극성용매, 헥산 또는 디크로로메탄의 비극성용매 또는 이들의 혼합용매를 사용할 수 있다. 또한, 바람직하게는 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합용매를 사용할 수 있으며, 보다 바람직하게는 에탄올을 사용할 수 있다. 본 발명의 일 실시예에서는 상기 용매로서 100% 에탄올을 이용하여 추출한 뒤 감압 농축한 단삼 추출물을 제조하였다.In the present invention, the extraction solvent may be water, an organic solvent or a mixed solvent thereof. The organic solvent may be an alcohol having 1 to 4 carbon atoms, a polar solvent such as ethyl acetate or acetone, a hexane or a dichloromethane A nonpolar solvent or a mixed solvent thereof may be used. Further, water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof may be preferably used, and more preferably ethanol can be used. In one embodiment of the present invention, the extract was extracted with 100% ethanol as the solvent, and then the extract was concentrated under reduced pressure.
본 발명에서의 용어, "apoptosis"는 세포자멸사라고도 하며, 일종의 계획된 세포 죽음(programmed cell death; PCD)으로서, 우리 몸 안에 입력되어 있는 생체 프로그램에 의해 비정상 세포, 손상된 세포, 노화된 세포가 스스로 자살해 사멸함으로써 전체적인 신체 건강을 유지하도록 하는 메커니즘이다. The term " apoptosis " in the present invention, also called apoptosis, is a kind of programmed cell death (PCD) in which abnormal cells, damaged cells, It is a mechanism to maintain overall physical health by decay.
본 발명에서의 용어, "예방"이란 본 발명에 따른 약학 조성물의 투여에 의해 암의 발생, 확산 및 재발을 억제 또는 지연시키는 모든 행위를 의미하고, "치료"란 상기 약학 조성물의 투여에 의해 암의 의심 및 발병 개체의 증상이 호전되거나 이롭게 변경하는 모든 행위를 의미한다.The term " prevention " in the present invention means all the actions of inhibiting or delaying the generation, spread and recurrence of cancer by the administration of the pharmaceutical composition according to the present invention, and " And all actions that alleviate or ameliorate the symptoms of the affected individuals.
본 발명에서의 용어, "치료학적으로 유효한 양"은 대상 질환을 예방 또는 치료하는데 유효한 약학적으로 허용 가능한 염의 양을 의미하며, 본 발명의 조성물의 치료적으로 유효한 양은 여러 요소, 예를 들면, 투여방법, 목적부위, 환자의 상태 등에 따라 달라질 수 있다. 따라서 인체에 사용 시 투여량은 안전성 및 효율성을 함께 고려하여 적정량으로 결정되어야 한다. 동물실험을 통해 결정한 유효량으로부터 인간에 사용되는 양을 추정하는 것도 가능하다. 유효한 양의 결정시 고려할 이러한 사항은, 예를 들면 Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed.(2001), Pergamon Press; 및 E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed.(1990), Mack Publishing Co.에 기술되어 있다.The term " therapeutically effective amount " in the present invention means an amount of a pharmaceutically acceptable salt effective to prevent or treat a target disease, and a therapeutically effective amount of the composition of the present invention may vary depending on various factors, The method of administration, the site of administration, the condition of the patient, and the like. Therefore, when used in humans, the dosage should be determined in an appropriate amount considering both safety and efficacy. It is also possible to estimate the amount used in humans from the effective amount determined through animal experiments. Such considerations in determining the effective amount are described, for example, in Hardman and Limbird, eds., Goodman and Gilman ' s Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; And E.W. Martin ed., Remington ' s Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.
본 발명의 약학 조성물은 약학적으로 유효한 양으로 투여한다. 본 발명에서 사용되는 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효용량 수준은 환자의 건강상태, 암의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와 순차적으로 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 상기한 요소들을 모두 고려하여, 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term " pharmaceutically effective amount " means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment and not causing side effects, Factors well known in the art and other medical disciplines including health status, type of cancer, severity, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration and rate of release, duration of treatment, ≪ / RTI > The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiply. Taking all of the above factors into consideration, it is important to administer an amount that can achieve the maximum effect in a minimal amount without side effects, which can be easily determined by those skilled in the art.
본 발명의 약학조성물은 생물학적 제제에 통상적으로 사용되는 담체, 희석제, 부형제 또는 둘 이상의 이들의 조합을 포함할 수 있다. 본 발명에서 사용되는 용어, "약학적으로 허용 가능한"이란 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미한다. 상기 담체는 조성물을 생체 내 전달에 적합한 것이면 특별히 제한되지 않으며, 예를 들면, Merck Index, 13th ed., Merck & Co. Inc. 에 기재된 화합물, 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로스 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 이용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한, 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주이용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당 분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(Mack Publishing Company, Easton PA, 18th, 1990)에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제 화할 수 있다.The pharmaceutical compositions of the present invention may include carriers, diluents, excipients, or a combination of two or more thereof commonly used in biological formulations. As used herein, the term " pharmaceutically acceptable " means that the composition is free of toxicity to cells or humans exposed to the composition. The carrier is not particularly limited as long as the composition is suitable for in vivo delivery, for example, Merck Index, 13th ed., Merck & Inc. A buffered saline solution, a buffer solution, a dextrose solution, a maltodextrin solution, glycerol, ethanol, and one or more of these components may be mixed and used, and if necessary, an antioxidant, a buffer, Conventional additives may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into main dosage forms such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules or tablets. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990) in a suitable manner in the art.
본 발명의 약학 조성물은 약학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니톨, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말셀룰로오스, 히드록시프로필셀룰로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바 납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당, 덱스트로스, 소르비톨 및 탈크 등이 사용될 수 있다. 본 발명에 따른 약학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 중량부 내지 90 중량부 포함되는 것이 바람직하나, 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, Wherein the starch is selected from the group consisting of lactose, mannitol, sugar, arabic gum, pregelatinized starch, cornstarch, powdered cellulose, hydroxypropyl cellulose, opaques, sodium starch glycolate, carnauba wax, synthetic aluminum silicate, stearic acid, magnesium stearate, Calcium, white sugar, dextrose, sorbitol and talc may be used. The pharmaceutically acceptable additive according to the present invention is preferably included in the composition in an amount of 0.1 part by weight to 90 parts by weight, but is not limited thereto.
본 발명의 약학 조성물은 유효성분으로서 단삼 추출물 이외에 공지된 항암제를 추가로 포함할 수 있고, 이들 질환의 치료를 위해 공지된 다른 치료와 병용될 수 있다. 다른 치료에는 화학요법, 방사선치료, 호르몬 치료, 골수 이식, 줄기-세포 대체치료, 다른 생물학적 치료, 면역치료 등이 포함되지만, 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention may further comprise a known anti-cancer agent other than the extract of Panax ginseng as an active ingredient, and may be used in combination with other therapies known for the treatment of these diseases. Other treatments include, but are not limited to, chemotherapy, radiation therapy, hormone therapy, bone marrow transplantation, stem cell replacement therapy, other biological therapies, immunotherapy, and the like.
본 발명의 약학 조성물에 포함될 수 있는 항암제의 예시에는 DNA 알킬화제(DNA alkylating agents)로 메클로에타민(mechloethamine), 클로람부칠(chlorambucil), 페닐알라닌(phenylalanine), 무스타드(mustard), 사이클로포스파미드(cyclophosphamide), 이포스파미드(ifosfamide), 카르무스틴(carmustine: BCNU), 로무스틴(lomustine: CCNU), 스트렙토조토신(streptozotocin), 부술판(busulfan), 티오테파(thiotepa), 시스플라틴(cisplatin) 및 카보플라틴(carboplatin); 항암 항생제(anti-cancer antibiotics)로 닥티노마이신(dactinomycin: actinomycin D), 독소루비신(doxorubicin: adriamycin), 다우노루비신(daunorubicin), 이다루비신(idarubicin), 미토크산트론(mitoxantrone), 플리카마이신(plicamycin), 마이토마이신 C(mitomycin C) 및 블레오마이신(bleomycin); 및 식물 알카로이드(plant alkaloids)로 빈크리스틴(vincristine), 빈블라스틴(vinblastine), 파클리탁셀(paclitaxel), 도세탁셀(docetaxel), 에토포시드(etoposide), 테니포시드(teniposide), 토포테칸(topotecan) 및 이리도테칸(iridotecan) 등이 포함되지만, 이에 한정되는 것은 아니다.Examples of anticancer agents that may be included in the pharmaceutical compositions of the present invention include DNA alkylating agents such as mechloethamine, chlorambucil, phenylalanine, mustard, cyclophosphamide, cyclophosphamide, ifosfamide, carmustine (BCNU), lomustine (CCNU), streptozotocin, busulfan, thiotepa, cisplatin ) And carboplatin; The anticancer antibiotics include dactinomycin (actinomycin D), doxorubicin (adriamycin), daunorubicin, idarubicin, mitoxantrone, Plicamycin, mitomycin C, and bleomycin; And plant alkaloids such as vincristine, vinblastine, paclitaxel, docetaxel, etoposide, teniposide, topotecan, And iridotecan, but are not limited thereto.
일 측면에서, 본 발명은 단삼 추출물을 이를 필요로 하는 개체에게 투여하는 단계를 포함하는, 암을 예방 또는 치료하는 방법에 관한 것이다.In one aspect, the present invention relates to a method of preventing or treating cancer, comprising administering the extract to a subject in need thereof.
본 발명에서 사용되는 용어, "개체"란, 상기 암이 발병하였거나 발병할 수 있는 인간을 포함한 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 메추라기, 고양이, 개, 마우스, 쥐, 토끼 또는 기니아 피그를 포함한 모든 동물을 의미하고, 본 발명의 약학 조성물을 개체에게 투여함으로써 상기 질환들을 효과적으로 예방 또는 치료할 수 있다. 본 발명의 약학 조성물은 기존의 치료제와 병행하여 투여될 수 있다.The term " individual " used in the present invention means a monkey, a horse, a sheep, a pig, a chicken, a turkey, a quail, a cat, a dog, a mouse, a rat, a rabbit Refers to all animals including guinea pigs, and the diseases can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to a subject. The pharmaceutical composition of the present invention can be administered in parallel with existing therapeutic agents.
본 발명에서 사용되는 용어, "투여"란, 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 목적하는 방법에 따라 비 경구 투여(예를 들어 정맥 내, 피하, 복강 내 또는 국소에 주사 제형으로 적용)하거나 경구 투여할 수 있으며, 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설률 및 질환의 중증도 등에 따라 그 범위가 다양하다. 본 발명의 조성물의 경구 투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 통상적으로 사용되는 단순 희석제인 물, 액체 파라핀 이외에 다양한 부형제, 예컨대 습윤제, 감미제, 방향제, 보존제 등이 함께 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제, 좌제 등이 포함된다. 본 발명의 약학 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수도 있다. 바람직한 투여방식 및 제제는 정맥 주사제, 피하 주사제, 피내주사제, 근육 주사제, 점적 주사제 등이다. 주사제는 생리식염액, 링겔액 등의 수성 용제, 식물유, 고급 지방산 에스테르(예, 올레인산에칠 등), 알코올 류(예, 에탄올, 벤질알코올, 프로필렌글리콜, 글리세린 등) 등의 비수성 용제 등을 이용하여 제조할 수 있고, 변질 방지를 위한 안정화제(예, 아스코르빈산, 아황산수소나트륨, 피로아황산나트륨, BHA, 토코페롤, EDTA 등), 유화제, pH 조절을 위한 완충제, 미생물 발육을 저지하기 위한 보존제 (예, 질산페닐수은, 치메로살, 염화벤잘코늄, 페놀, 크레솔, 벤질알코올 등) 등의 약학적 담체를 포함할 수 있다.The term " administering " as used herein means providing a predetermined substance to a patient in any appropriate manner, and may be administered orally or parenterally (for example, by intravenous, subcutaneous, The dosage may vary depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of the disease. Examples of the liquid preparation for oral administration of the composition of the present invention include suspensions, solutions, emulsions, syrups, and the like. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, Etc. may be included together. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like. The pharmaceutical composition of the present invention may be administered by any device capable of moving the active substance to the target cell. The preferred modes of administration and formulations are intravenous, subcutaneous, intradermal, intramuscular, and drip injections. The injectable solution may be a non-aqueous solvent such as an aqueous solvent such as a physiological saline solution or a ring gel solution, a vegetable oil, a higher fatty acid ester (e.g., oleic acid), an alcohol (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.) (For example, ascorbic acid, sodium hydrogen sulfite, sodium pyrophosphate, BHA, tocopherol, EDTA and the like), an emulsifier, a buffer for pH control, a microbial growth inhibitor And a pharmaceutical carrier such as a preservative (e.g., mercury nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.).
본 발명은 단삼 추출물을 유효성분으로 포함하는 항암보조제에 관한 것이다.The present invention relates to an anti-cancer adjuvant comprising an extract of Panax ginseng as an active ingredient.
본 발명의 용어, "항암보조제"는 항암제의 항암효과를 증대시키고, 항암제의 부작용을 억제하거나 개선시키 위하여 사용될 수 있으며, 항암제와 병용하여 환자에게 투여될 수 있다. The term " anticancer adjuvant " of the present invention can be used to increase the anticancer effect of an anticancer agent, to suppress or improve side effects of the anticancer agent, and to administer it to a patient in combination with an anticancer agent.
본 발명은 단삼 추출물을 함유하는 암의 예방 또는 개선용 식품 조성물에 관한 것이다.The present invention relates to a food composition for preventing or ameliorating a cancer containing Rhodococcus extract.
본 발명의 조성물을 식품 조성물로 사용하는 경우, 상기 단삼 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상의 방법에 따라 적절하게 사용할 수 있다. 상기 조성물은 유효성분 이외에 식품학적으로 허용 가능한 식품보조첨가제를 포함할 수 있으며, 유효성분의 혼합량은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.When the composition of the present invention is used as a food composition, the extract can be used as it is, or it can be used together with other food or food ingredients, and can be appropriately used according to ordinary methods. The composition may contain a food-acceptable food-aid additive in addition to the active ingredient, and the amount of the active ingredient to be mixed may be suitably determined according to the intended use (prevention, health or therapeutic treatment).
본 발명의 용어, "식품보조첨가제"는 식품에 보조적으로 첨가될 수 있는 구성요소를 의미하며, 각 제형의 건강기능식품을 제조하는데 첨가되는 것으로서 당업자가 적절히 선택하여 사용할 수 있다. 식품보조첨가제의 예로는 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등이 포함되지만, 상기 예들에 의해 본 발명의 식품보조첨가제의 종류가 제한되는 것은 아니다.The term " food supplementary additive " of the present invention means a component which can be added to food, and it can be appropriately selected and used by those skilled in the art as added to produce health functional food of each formulation. Examples of food-aid additives include flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, , a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol, and a carbonating agent used in a carbonated drink. However, the types of the food auxiliary additives of the present invention are not limited by these examples.
본 발명의 식품 조성물에는 건강기능식품이 포함될 수 있다. 본 발명에서 사용되는 용어 "건강기능식품"이란 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 정제, 캅셀, 분말, 과립, 액상 및 환 등의 형태로 제조 및 가공한 식품을 말한다. 여기서 '기능성'이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 건강기능식품은 통상의 기술 분야에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조 시에는 통상의 기술 분야에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 건강기능식품의 제형 또한 건강기능식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품용 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 건강기능식품은 항암제의 효과를 증진시키기 위한 보조제로 섭취가 가능하다.A health functional food may be included in the food composition of the present invention. The term " health functional food " as used in the present invention refers to a food prepared and processed in the form of tablets, capsules, powders, granules, liquids and rings using raw materials and components having useful functions in the human body. Here, 'functional' refers to the structure and function of the human body to obtain nutritional effects and obtain useful effects for health use such as physiological action. The health functional food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components which are usually added in the conventional technical fields. In addition, the formulation of the health functional food may also be produced without limitation as long as the formulation is recognized as a health functional food. The composition for food of the present invention can be manufactured in various forms, and unlike general pharmaceuticals, it has the advantage that there is no side effect that may occur when a drug is used for a long period of time, and is excellent in portability, Can be ingested as an adjuvant to enhance the effectiveness of anticancer drugs.
또한, 본 발명의 조성물이 사용될 수 있는 건강식품의 종류에는 제한이 없다. 아울러 본 발명의 단삼 추출물을 활성성분으로 포함하는 조성물은 당업자의 선택에 따라 건강기능식품에 함유될 수 있는 적절한 기타 보조 성분과 공지의 첨가제를 혼합하여 제조할 수 있다. 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림 류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 본 발명에 따른 추출물을 주성분으로 하여 제조한 즙, 차, 젤리 및 주스 등에 첨가하여 제조할 수 있다.There is no limitation on the kind of health food to which the composition of the present invention can be used. In addition, the composition comprising the extract of Dansamp extract of the present invention as an active ingredient may be prepared by mixing other suitable auxiliary ingredients and known additives, which may be contained in health functional foods, according to the selection of a person skilled in the art. Examples of foods that can be added include dairy products, such as meat, sausage, bread, chocolates, candies, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Vitamin complex, and the like, and can be prepared by adding to the juice, tea, jelly, and juice prepared from the extract of the present invention as a main component.
본 발명의 단삼 추출물은 천연 식물을 원료로 하므로 약학 조성물 또는 식품 조성물로 사용할 경우에도 일반적인 합성 화합물에 비하여 부작용이 덜할 수 있으므로, 안전하게 약학 조성물 및 건강기능식품에 포함되어 유용하게 사용될 수 있다.Since the extract of Dansamp ginseng according to the present invention is used as a pharmaceutical composition or a food composition due to the use of a natural plant as a raw material, it can be safely contained in a pharmaceutical composition and a health functional food safely.
이하, 본 발명을 실시예를 통하여 더욱 상세히 설명하기로 한다. 이들 실시예는 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to examples. These examples are for further illustrating the present invention, and the scope of the present invention is not limited to these examples.
실시예Example 1. One. 단삼Sansam (( Salvia Salvia miltiorrhizamiltiorrhiza ) 추출물 제조) Preparation of extract
단삼 추출물은 100% 에탄올로 단삼을 추출한 뒤 감압 농축하여 단삼 에탄올 추출물을 제조하였다.The extracts of Panax ginseng extracts were extracted with 100% ethanol and concentrated under reduced pressure.
실시예Example 2. 세포배양 2. Cell culture
다발성 골수종 세포주인 U937 세포주(한국세포주은행) 50㎕를 96웰-플레이트에 2×104 세포/웰이 되도록 분주한 뒤, 10% 불활성된 FBS(fetal bovine serum) 및 1% 페니실린-스트렙토마이신을 첨가한 RPMI 배지를 이용하여 37℃, 5% CO2 인큐베이터 (MCO-15AC, Sanyo, Osaka, Japan)에서 배양되었다. 50 占 퐇 of U937 cell line (Korean Cell Line Bank), which is a multiple myeloma cell line, was divided into 96 well-plates so as to be 2 占04 cells / well, and then 10% inactivated FBS (fetal bovine serum) and 1% penicillin- (MCO-15AC, Sanyo, Osaka, Japan) using an RPMI medium supplemented with 5% CO 2 at 37 ° C.
실시예Example 3. 3. 단삼Sansam 추출물의 다발성 골수종에 대한 세포독성 결과 Cytotoxic effect of extract on multiple myeloma
본 발명자들은 단삼 추출물에 의한 다발성 골수종 세포에서의 세포독성을 확인하기 위한 실험을 수행하였다. 단삼 추출물은 0, 12.5, 25, 50, 100, 200 및 400㎍/ml의 농도로 다발성 골수종 세포주인 U937 세포에 각각 50㎕씩 처리한 뒤, 하루 동안 배양하였고, 암상태에서 배양된 세포에 EZ-Cytox 시약 (DoGen)을 10㎕ 처리하여 30분 내지 4시간 동안 인큐베이션한 뒤, 마이크로플레이트 리더기(Bio-rad Model 680)를 이용하여 450nm에서 흡광도를 측정하였다. The present inventors carried out an experiment to confirm cytotoxicity in multiple myeloma cells by the extract of Dansamp extract. The extracts of Dansamp extract were treated with U137 cells at a concentration of 0, 12.5, 25, 50, 100, 200 and 400 ㎍ / ml, respectively, and the cells were cultured for one day. After incubation for 30 minutes to 4 hours, the absorbance was measured at 450 nm using a microplate reader (Bio-rad Model 680).
그 결과, 단삼 추출물은 농도 의존적으로 다발성 골수종 세포에 세포독성을 유도함을 확인하였다(도 1).As a result, it was confirmed that the extracts of Rana ginseng induce cytotoxicity in multiple myeloma cells in a concentration-dependent manner (Fig. 1).
실시예Example 4. 4. 단삼Sansam 추출물에 의한 활성 산소( Active oxygen by extract ( ROSROS , reactive oxygen species) 유도 효과, reactive oxygen species
본 발명자들은 단삼 추출물에 의해 ROS를 증가시켜 ER(endoplasmic reticulum)-스트레스를 유발하는지 여부를 확인하기 위하여, 단삼 추출물에 의하여 활성 산소의 생성량이 증가되는지를 확인하는 실험을 수행하였다. 활성 산소는 DCFDA Cellular Reactive Oxygen Species Detection Assay Kit (abcam)를 이용하여 측정하였다. 구체적으로, 다발성 골수종 세포주인 U937 세포주 4×105개를 PBS로 세정한 뒤, 20mM의 DCDFA를 처리하여 37℃에서 암상태로 30분 동안 인큐베이션하고, 다시 PBS로 세정하였다. 이후, 2×104개의 세포 (50㎕)를 96웰-플레이트에 분주하고, 상기 실시예 1에서 제조된 단삼 추출물 50㎕을 0, 50 및 100㎍/ml의 농도로 각각 처리한 뒤, 6시간 동안 암상태에서 인큐베이션하였다. 그 후, 마이크로플레이트 리더기를 이용하여 485/535nm에서 흡광도를 측정하였다.The present inventors carried out an experiment to ascertain whether the production of reactive oxygen species (ROS) is increased by the extract of Rana ginseng extract in order to ascertain whether or not ER (endoplasmic reticulum) Active oxygen was measured using the DCFDA Cellular Reactive Oxygen Species Detection Assay Kit (abcam). Specifically, 4 × 10 5 U937 cell lines, which were multiple myeloma cell lines, were washed with PBS, treated with 20 mM DCDFA, incubated at 37 ° C. for 30 minutes in a dark state, and washed again with PBS. Then, 2 × 10 4 cells (50 μl) were dispensed into a 96-well plate, and 50 μl of the extract prepared in Example 1 was treated at a concentration of 0, 50, and 100 μg / ml, ≪ / RTI > for a period of time. After that, the absorbance was measured at 485/535 nm using a microplate reader.
그 결과, 50 또는 100㎍/ml의 단삼 추출물을 처리한 경우 다발성 골수종 세포에서 활성 산소의 생성량이 증가됨을 확인하였다(도 2). As a result, it was confirmed that the production of active oxygen was increased in multiple myeloma cells when 50 or 100 μg / ml of ginseng extract was treated (FIG. 2).
따라서, 단삼 추출물은 활성 산소의 생성량을 증가시켜 ER-스트레스를 유발하고 이에 의해 다발성 골수종 세포의 세포사멸을 유도함으로써 상기 질환을 치료할 수 있음을 확인하였다. Therefore, it was confirmed that the extracts of Rana cv. Ganjang increased the production of reactive oxygen species and induced ER-stress, thereby inducing cell death of multiple myeloma cells.
실시예Example 5. 5. 단삼Sansam 추출물에 의한 단백질 발현 분석 결과 Analysis of Protein Expression by Extract
본 발명자들은 활성 산소의 생성량을 증가시키는 기작을 확인하는 실험을 수행하였다. 우선, CHOP(CCAAT/-enhancer-binding protein homologous protein)은 전사인자로서 ER-스트레스에 의해 유도되는 세포사멸의 중요한 중개자로서 알려져 있어(Antioxid Redox Signal. 2015 Nov 20;23(15):1233-45), 단삼 추출물에 의하여 CHOP의 발현이 증가되는지 여부를 확인하였다. 또한, 미토콘드리아의 손상에 의한 세포사멸 관련인자로서 Caspase 및 PARP(Poly ADP ribose polymerase)이 알려져 있어, 본 실험에서는 단삼 추출물에 의하여 세포사멸 진행시 절단되는 것으로 알려진 PARP의 발현량(cleaved PARP)이 증가되는지 여부를 확인하는 실험을 수행하였다. The present inventors have conducted experiments to confirm the mechanism of increasing the production of active oxygen. First, CHOP (CCAAT / -enhancer-binding protein homologous protein) is known as an important mediator of ER-stress induced apoptosis as a transcription factor (Antioxid Redox Signal. 2015 Nov 20; 23 (15): 1233-45 ), And whether or not the expression of CHOP was increased by the extract of radish ginseng. In addition, Caspase and PARP (Poly ADP ribose polymerase) are known as apoptosis-related factors due to damage to mitochondria. In this experiment, cleaved PARP, which is known to be cleaved in the course of apoptosis, The results are summarized as follows.
상기 단백질의 발현량의 확인은 웨스턴블럿팅 방법에 의하였다. 우선, 다발성 골수종 세포주인 U937 세포주에 상기 실시예 1에서 제조된 단삼 추출물을 0, 50 및 100㎍/ml로 각각 처리하고, 24시간 동안 37℃, 5% CO2 인큐베이터에서 배양하였다. 그 후, 세포를 수집하여 PBS로 세척하고, RIPA 버퍼(20mM Tris-HCL (pH 7.5), 150mM Nacl, 1mM NaEDTA, 1mM EGTA, 1% NP-40, 1% sodium pyrpphophate, 1mM beta-glycerophosphate, 1mM Na3VO4 및 1ug/ml leupeptin (Cell signaling))를 첨가하여 30분간 4℃에서 세포를 용해하였다. 세포 용해물은 15,520×g에서 20분간 원심분리하여 세포막 성분 등을 제거한 후 RC DC™ Protein Assay Kit II(protein assay kit) (Bio-rad, USA)를 사용하여 단백질을 정량하여 시료별 (단삼 추출물 0, 50 및 100㎍/ml 처리군들)로 동일한 단백질의 양이 포함되도록 조절하였다. 준비된 단백질 시료에 5×loading dye를 넣고 5분 동안 100℃로 가열하여 단백질을 변성시켰다. 그 후, 10% SDS-PAGE 젤에 시료를 로딩하여 100V로 2시간 동안 전기영동을 수행하였으며, 젤 위에서 분리된 단백질들을 280mA로 2시간 동안 멤브레인으로 트랜스퍼하였다. 트랜스퍼된 멤브레인은 3% 스킴 밀크가 포함된 TBST (tris buffered saline, pH 7.5) 용액으로 상온에서 30분 동안 블로킹한 뒤, 1차 항체인 anti-cleaved-PARP (cell signaling), anti-CHOP (cell signaling)을 각각 1:500으로 희석하여 4℃에서 오버나잇으로 반응시켰다. TBST로 2회 세정한 뒤 2차 항체인 HRP(horseradish peroxidase)가 결합된 anti-rabbit 과 mouse IgG를 1:10,000으로 희석하여 상온에서 1시간 동안 반응시킨 다음, TBST로 2회 세정하였다. 세정한 멤브레인에 chemiluminescent reagent를 넣어 1 내지 3분 동안 반응시키고 필름에 감광하여 단백질 밴드를 가시화하였다.The amount of expression of the protein was determined by the Western blotting method. First, the extract of Dansamp extract prepared in Example 1 was treated at 0, 50, and 100 / / ml, respectively, in a U937 cell line, which is a multiple myeloma cell line, and cultured in a 5% CO 2 incubator at 37 캜 for 24 hours. Cells were then harvested, washed with PBS and resuspended in RIPA buffer (20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 1 mM NaEDTA, 1 mM EGTA, 1% NP-40, 1% sodium pyrpphophate, 1 mM beta-glycerophosphate, Na 3 VO 4 And 1 ug / ml leupeptin (Cell signaling)) was added and the cells were lysed at 4 캜 for 30 minutes. Cell lysates were centrifuged at 15,520 × g for 20 min to remove cell membrane components, and proteins were quantified using RC DC ™ Protein Assay Kit II (Bio-Rad, USA) 0, 50 and 100 [mu] g / ml treated groups). 5 × loading dye was added to the prepared protein sample, and the protein was denatured by heating to 100 ° C. for 5 minutes. Thereafter, the sample was loaded on a 10% SDS-PAGE gel, electrophoresed at 100 V for 2 hours, and proteins separated from the gel were transferred to the membrane at 280 mA for 2 hours. The transferred membrane was blocked with TBST (tris buffered saline, pH 7.5) solution containing 3% skim milk for 30 minutes at room temperature and then incubated with primary anti-cleaved PARP (cell signaling), anti-CHOP signaling) were diluted 1: 500 and reacted overnight at 4 ° C. After washing twice with TBST, anti-rabbit and mouse IgG conjugated with HRP (secondary horseradish peroxidase) were diluted 1: 10,000, reacted at room temperature for 1 hour, and washed twice with TBST. The chemiluminescent reagent was added to the washed membrane for 1 to 3 minutes, and the protein band was photographed to visualize the protein band.
상기 웨스턴블럿팅 실험 결과, 50 및 100㎍/ml의 단삼 추출물을 처리한 경우 농도-의존적으로 cleaved-PARP 및 CHOP 단백질의 발현량이 증가됨을 확인하였다(도 3). As a result of the Western blotting experiment, it was confirmed that when the extracts of 50 and 100 μg / ml were treated with the extract, the amount of cleaved-PARP and CHOP protein was increased in a concentration-dependent manner (FIG. 3).
따라서, 본 발명자들은 단삼 추출물이 cleaved-PARP 및 CHOP 단백질의 발현량을 증가시키고, 이로써 활성 산소의 생성량을 증가되어 ER-스트레스를 유발하고 이에 의해 다발성 골수종 세포의 세포사멸을 유도함으로써 상기 질환을 치료할 수 있음을 확인하였다. Accordingly, the present inventors have found that the extract of Dansamp extract increases the expression amount of cleaved-PARP and CHOP protein, thereby increasing the production amount of reactive oxygen species, thereby inducing ER-stress, thereby inducing apoptosis of multiple myeloma cells Respectively.
Claims (9)
상기 추출물은 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 추출한 것을 특징으로 하는 조성물.The method according to claim 1,
Wherein the extract is extracted with water, an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.
상기 추출물의 농도는 10 내지 200 ㎍/ml 인 것을 특징으로 하는 조성물.The method according to claim 1,
Wherein the concentration of said extract is from 10 to 200 [mu] g / ml.
상기 추출물은 암세포의 소포체(endoplasmic reticulum, ER) 스트레스로 인한 세포사멸을 유도하는 것을 특징으로 하는 조성물.The method according to claim 1,
Wherein said extract induces apoptosis due to endoplasmic reticulum (ER) stress of cancer cells.
상기 추출물은 활성 산소(reactive oxygen species, ROS)의 생성량을 증가시키는 것을 특징으로 하는 조성물. The method according to claim 1,
Wherein the extract increases the amount of reactive oxygen species (ROS) produced.
상기 추출물은 cleaved-PARP(Poly ADP ribose polymerase) 및 CHOP(CCAAT/-enhancer-binding protein homologous protein)의 발현량을 증가시키는 것을 특징으로 하는 조성물. The method according to claim 1,
Wherein the extract increases the expression level of cleaved-PARP (Poly ADP ribose polymerase) and CHOP (CCAAT / -enhancer-binding protein homologous protein).
A food composition for preventing or ameliorating multiple myeloma or leukemia comprising extracts of Panax ginseng as an active ingredient.
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