KR101586054B1 - Composition for preventing or treating cancer containing METRNL (meteorin-like) - Google Patents
Composition for preventing or treating cancer containing METRNL (meteorin-like) Download PDFInfo
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- KR101586054B1 KR101586054B1 KR1020150163432A KR20150163432A KR101586054B1 KR 101586054 B1 KR101586054 B1 KR 101586054B1 KR 1020150163432 A KR1020150163432 A KR 1020150163432A KR 20150163432 A KR20150163432 A KR 20150163432A KR 101586054 B1 KR101586054 B1 KR 101586054B1
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- Prior art keywords
- meteorin
- cancer
- analog
- preventing
- breast cancer
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Abstract
Description
본 발명은 메테오린-유사체를 유효성분으로 함유하는 암 예방용 또는 치료용 조성물에 관한 것으로, 더욱 상세하게는 유방암세포, 대장암세포 또는 자궁경부암세포의 세포 사멸을 유도하고 세포 증식을 억제하는 조성물에 관한 것이다.
TECHNICAL FIELD The present invention relates to a composition for preventing or treating cancer comprising a meteorin-analog as an active ingredient, and more particularly to a composition for inducing apoptosis and inhibiting cell proliferation of a breast cancer cell, a colon cancer cell or a cervical cancer cell .
유방암의 치료는 주로 외과적 수술, 방사선 치료, 또는 화학요법 중에서 한 가지 또는 이들을 조합하여 이루어지고 있다. 그런데, 유방 절제 수술은 여성들에게 상실에 따른 심리적 충격을 주어 우울감과 대인기피증에 따른 신경정신과 진료가 요구되는 부작용이 있다. 방사선 치료는 작게는 피부나 식도의 염증을 발생시키며, 폐렴, 심근 손상, 림프부종과 같은 부작용을 동반하는 단점이 있다. 항암제를 이용한 화학요법은 환자들이 거부반응 없이 치료에 응하는 장점이 있으며, 외과적 수술 전후의 보조 요법으로 사용됨으로 항암제 개발을 위한 노력이 꾸준하게 이루어지고 있다.The treatment of breast cancer is usually performed by one or a combination of surgical operations, radiation therapy, or chemotherapy. However, mastectomy has the side effect of giving psychological shock to women due to loss, which requires neuropsychiatric consultation according to depression and interpersonal grieving. Radiation therapy causes inflammation of the skin or esophagus, and has the disadvantage of accompanying side effects such as pneumonia, myocardial damage, and lymphatic edema. Chemotherapy using anticancer drugs has advantages in that patients respond to treatment without rejection, and it is used as an adjunct therapy before and after surgical operation, so efforts for development of anticancer drugs have been made steadily.
항암제를 이용한 치료는 유방암의 종류에 따라 다양하게 이루어지고 있다. 유방암 세포의 증식에 호르몬이 관여한다는 것이 알려짐에 따라, 에스트로젠 수용체가 양성인 유방암의 경우, 이 수용체에 작용하는 타목시펜을 사용한다. 또한, 에스트로젠의 생성을 저해하는 아로마타아제 저해제를 사용할 수 있다. 그러나 타목시펜은 최장 10년 사용할 것을 권고하고 있으며, 아로마타아제는 폐경기 이후의 여성에 한하여 효과를 보이는 것으로 보고되어 있다.Treatment with anticancer drugs varies according to the type of breast cancer. As it is known that hormone is involved in the proliferation of breast cancer cells, in the case of breast cancer positive for estrogen receptor, tamoxifen acting on this receptor is used. In addition, an aromatase inhibitor which inhibits the production of estrogen can be used. However, tamoxifen is recommended to be used for up to 10 years, and aromatase has been reported to be effective only for postmenopausal women.
에스트로젠 수용체가 음성인 유방암의 경우는 싸이클로포스파마이드, 독소루비신, 플르오로우라실 및 탁센계열의 약물이 이용된다. 그러나 이러한 약물은 암세포의 특징인 빠른 성장과 빠른 증식을 저해하도록 고안되었으므로 빠르게 성장하는 정상세포에도 심각한 부작용을 야기한다. 또한 이 약물들은 정상세포의 DNA 손상을 유발할 수 있으며, 독소루비신의 경우에는 심근세포의 손상을 야기하는 것으로 보고되어 있다. In the case of breast cancer in which the estrogen receptor is negative, cyclophosphamide, doxorubicin, fluorouracil and taxane-based drugs are used. However, these drugs are designed to inhibit rapid growth and rapid proliferation, which are characteristic of cancer cells, and cause serious adverse effects on rapidly growing normal cells. It is also reported that these drugs can cause DNA damage in normal cells, and in the case of doxorubicin, damage to myocardial cells.
몇몇 유방암에서는 HER2의 활성이 암세포의 증식을 유도하고, 재발에 관여하며, 예후에 좋지 않은 영향을 준다는 것이 알려져 HER2에 대한 항체인 허셉틴을 사용하기도 한다. 그러나 허셉틴은 비교적 고가이며 심장에 손상을 주는 것으로 보고되어 있다. 더구나, HER2는 과발현된 환자에 한하여 효과를 보이고 있다.In some breast cancers, the activity of HER2 is known to induce proliferation of cancer cells, involve recurrence, and adversely affect prognosis, so that Herceptin, an antibody against HER2, may be used. However, Herceptin is relatively expensive and has been reported to damage the heart. Furthermore, HER2 has been shown to be effective only in over-exposed patients.
이렇듯, 지금까지 이용되고 있는 항암제들은 폐경기 이후의 환자에게 치료 효과를 보이든지, 에스트로젠 수용체 또는 HER2를 발현하는 유방암의 경우에 효과적이든지, 사용 기간을 한정해야한다는 한계를 가지고 있다. 더불어, 정상 세포에 부작용을 나타내거나 심장에 대한 부작용을 나타내는 단점을 내포하고 있어 유방암에 대한 새로운 항암제 개발은 계속 요구되고 있다.Thus, anticancer drugs used so far have limitations in that they are effective for postmenopausal patients, effective for breast cancer expressing estrogen receptors or HER2, or limited in duration of use. In addition, there is a continuing demand for the development of new anticancer drugs for breast cancer because it has the disadvantage of showing adverse effects on normal cells or adverse effects on the heart.
운동과 같은 신체 활동이 유방암을 감소시킨다는 사실이 임상보고를 비롯하여 다수 알려져 왔으며 (Rockhill B et al., Arch Intern Med, 159(19):2290-2296, 1999; Loprinzi PD et al., Oncol Nurs Forum, 39(3):269-274, 2012), 유방암에 대한 운동의 항암효과는 근육에서 분비된 마이오카인 (myokine)의 작용에 의한 것일 가능성이 제시되었다 (Gannon NR et al., Int J Cancer, 136(4):E197-202, 2015; Hojman P et al., J Physiol Endocrinol Metab, 301(3):E504-10, 2011).Many studies have shown that physical activity, such as exercise, reduces breast cancer, including clinical reports (Rockhill B et al., Arch Intern Med, 159 (19): 2290-2296, 1999; Loprinzi PD et al., Oncol Nurs Forum , 39 (3): 269-274, 2012), suggesting that the anticancer effect of exercise on breast cancer may be due to the action of myokine secreted from muscle (Gannon NR et al., Int J Cancer , 136 (4): E197-202, 2015; Hojman P et al., J Physiol Endocrinol Metab , 301 (3): E504-10, 2011).
메테오린-유사체 (meteorin-like, METRNL)는 마이오카인의 하나로 메테오린 계열에 속하며 311개의 아미노산으로 이루어져 있다. 메테오린-유사체는 신경계 질환 치료제로 보고되어 있으며 (US 8334264), 에너지 항상성, 조직 염증반응에 관여하는 것으로 알려져 대사성 또는 염증성 질환에 대한 치료제 후보로 제안되어 있다 (Rao RR et al., Cell, 157 (6):1279-1291). 그런데, 메테오린-유사체가 암 치료 효과가 있고 (KR-10-2014-0068148), 비만-관련된 암에 효과가 있는 것 (WO 2014-116556)으로 보고되어 있으나 유방암, 대장암, 자궁경부암에 대한 항암효과는 전혀 알려진 바가 없다. Meteorin-like (METRNL) is one of the mycokines, belonging to the meteorin family and consists of 311 amino acids. Meteorin-analogs have been reported to treat neurological diseases (US 8334264) and are known to be involved in energy homeostasis, tissue inflammatory responses and have been proposed as candidates for therapeutic treatment of metabolic or inflammatory diseases (Rao RR et al., Cell , 157 (6): 1279-1291). However, meteorin-analogs have been reported to be effective in treating cancer (KR-10-2014-0068148) and have been shown to be effective against obesity-related cancers (WO 2014-116556), but have been shown to be effective against breast, colon, The anticancer effect is not known at all.
한편, 메테오린 (meteorin)의 유방암에 대한 항암 용도가 보고되어 있으나 (KR 10-0823156), 메테오린은 피하 지방 조직에서 발견되지 않는데 비해 메테오린-유사체는 발현되는 것이 확인되어 두 단백질 간의 기능적 차이가 분명히 존재할 것으로 예상된다 (Li et al., CNS Neurosce Ther 20(4):344-354, 2014).On the other hand, meteorin has been reported to be used for anti-cancer treatment of breast cancer (KR 10-0823156), but meteorin was not found in subcutaneous adipose tissue, but meteorin-analog was found to be expressed, (Li et al., CNS Neurosce Ther 20 (4): 344-354, 2014).
이에, 본 발명자들은 상기 기술한 기존 항암제의 부작용을 개선한 새로운 항암제를 개발하고자 노력한 결과, 메테오린-유사체는 정상 세포에는 영향을 주지 않으면서, 유방암세포, 대장암세포 또는 자궁경부암세포의 세포 사멸 유도 및 세포 증식 억제 효과를 나타내는 것을 확인하고, 본 발명을 완성하게 되었다.
Accordingly, the present inventors have made efforts to develop a novel anticancer agent that improves the side effects of the conventional anticancer agents described above. As a result, the present inventors have found that meteorin-analogs can induce apoptosis of breast cancer cells, colorectal cancer cells or cervical cancer cells And the cell proliferation inhibitory effect, thereby completing the present invention.
본 발명의 목적은 암세포의 세포 사멸 유도와 세포 증식 억제 효과를 가지는 유방암, 자궁경부암, 또는 대장암에 대한 항암용 약학 조성물 및 식품을 제공하는데 있다.
It is an object of the present invention to provide an anticancer pharmaceutical composition and food for breast cancer, cervical cancer, or colorectal cancer, which have induction of cell death and inhibition of cell proliferation of cancer cells.
상기 목적을 달성하기 위하여, 본 발명은 서열번호 1의 아미노산 서열로 표시되는 메테오린-유사체를 유효성분으로 함유하는 유방암, 대장암, 및 자궁경부암으로 구성된 군에서 선택되는 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 selected from the group consisting of breast cancer, colon cancer, and cervical cancer containing the meteorin-analogue represented by the amino acid sequence of SEQ ID NO: 1 as an active ingredient Lt; / RTI >
본 발명은 또한, 서열번호 1의 아미노산 서열로 표시되는 메테오린-유사체를 유효성분으로 함유하는 유방암, 대장암, 및 자궁경부암으로 구성된 군에서 선택되는 암의 예방 또는 개선용 건강기능식품을 제공한다.
The present invention also provides a health functional food for preventing or ameliorating cancer selected from the group consisting of breast cancer, colon cancer, and cervical cancer, which contains, as an active ingredient, a methelin-analogue represented by the amino acid sequence of SEQ ID NO: 1 .
본 발명에 따르면, 메테오린-유사체는 암세포의 세포 사멸을 유도하고 세포 증식을 억제함으로, 유방암, 대장암, 자궁경부암의 예방 또는 치료하는데 유용하게 이용될 수 있다.
According to the present invention, the meteorin-analog can be useful for preventing or treating breast cancer, colon cancer, and cervical cancer by inducing apoptosis and inhibiting cell proliferation of cancer cells.
도 1은 메테오린-유사체에 의한 유방암 세포주의 세포 사멸을 측정한 것이다. (A) 아넥신 파이브 (annexin V); (B) 캐스페이즈3 (caspase3).
도 2는 메테오린-유사체에 의한 유방암 세포주의 생존율을 측정한 것이다.
도 3은 유방암 세포주에서, 메테오린-유사체에 의한 caspase-3의 발현을 나타낸 것이다.
도 4는 메테오린-유사체에 의한 유방암 세포주의 세포주기를 측정한 것이다.
도 5는 메테오린-유사체에 의한 정상 세포주의 생존율을 측정한 것이다.
도 6은 메테오린-유사체에 의한 대장암 세포주 또는 자궁경부암 세포주의 생존율을 측정한 것이다.
도 7은 메테오린-유사체에 의한 췌장암, 신경암 및 난소암 세포주의 생존율을 측정한 것이다.
도 8은 인간 메테오린-유사체 또는 마우스 메테오린-유사체에 의한 유방암 세포주의 생존율을 측정한 것이다.
도 9는 메테오린 또는 메테오린-유사체에 의한 유방암 세포주의 생존율과 p21단백질의 발현을 측정한 것이다.FIG. 1 shows the cell death of a breast cancer cell line by meteorin-analog. (A) annexin V; (B) Caspase 3 (caspase 3).
Figure 2 shows the survival rate of breast cancer cell lines by meteorin-analog.
Figure 3 shows the expression of caspase-3 by meteorin-analog in breast cancer cell lines.
Fig. 4 shows the cell cycle of a breast cancer cell line by meteorin-analog.
FIG. 5 shows the survival rate of a normal cell line by meteorin-analog.
6 is a graph showing the survival rate of colon cancer cell line or cervical cancer cell line by meteorin-analog.
FIG. 7 shows the survival rates of petechia, neural, and ovarian cancer cell lines by meteorin-analog.
Figure 8 shows the survival rate of breast cancer cell lines by human meteorin-analog or murine meteorin-analog.
FIG. 9 shows the survival rate of breast cancer cell lines and the expression of p21 protein by meteorin or meteorin-analog.
다른 식으로 정의되지 않는 한, 본 명세서에서 사용된 모든 기술적 및 과학적 용어들은 본 발명이 속하는 기술 분야에서 숙련된 전문가에 의해서 통상적으로 이해되는 것과 동일한 의미를 갖는다. 일반적으로, 본 명세서에서 사용된 명명법은 본 기술 분야에서 잘 알려져 있고 통상적으로 사용되는 것이다.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In general, the nomenclature used herein is well known and commonly used in the art.
본 발명에서는, 유방암 세포에 메테오린-유사체를 처리하여 세포 사멸과 세포 증식을 분석하였다. 세포 사멸을 분석한 결과, annexin V의 활성이 증가하며, caspase3의 활성이 농도 의존적으로 증가하는 것으로 나타나 메테오린-유사체가 세포 사멸을 유도한다는 것을 확인하였다. 그리고, 세포 증식을 분석한 결과, p21 단백질의 발현이 증가하고 세포 주기 G1 기의 세포가 많아짐으로 메테오린-유사체가 세포 증식을 억제한다는 것을 확인하였다. 또한, 대장암 세포와 자궁경부암 세포에서 메테오린-유사체 처리에 의해 세포 사멸이 증가하는 것을 확인함으로써 메테오린-유사체의 유방암, 대장암, 자궁경부암에 대한 예방 또는 치료 효과를 규명하였다.
In the present invention, mammalian cells were treated with meteorin-analog to analyze cell death and cell proliferation. Analysis of apoptosis revealed that the activity of annexin V was increased and the activity of
따라서, 본 발명은 일 관점에서, 서열번호 1의 아미노산 서열로 표시되는 메테오린-유사체를 유효성분으로 함유하는 유방암, 대장암, 및 자궁경부암으로 구성된 군에서 선택되는 암의 예방 또는 치료용 약학 조성물에 관한 것이다.Accordingly, in one aspect, the present invention provides a pharmaceutical composition for preventing or treating cancer selected from the group consisting of breast cancer, colon cancer, and cervical cancer, which comprises the methenin-analogue represented by the amino acid sequence of SEQ ID NO: 1 as an active ingredient .
본 발명에 있어서, 상기 메테오린-유사체는 암세포 증식을 억제하거나 또는 암세포 사멸을 유도하는 것을 특징으로 할 수 있다.In the present invention, the meteorin-analog may be characterized by inhibiting cancer cell proliferation or inducing cancer cell death.
본 발명에 있어서, 상기 메테오린-유사체는 p21 단백질 활성을 조절하여 암세포 증식을 억제하거나 또는 Caspase3의 활성을 조절하여 암세포 사멸을 유도하는 것을 특징으로 할 수 있다.In the present invention, the methorein-analog may be characterized by inhibiting cancer cell proliferation by modulating p21 protein activity or inducing cancer cell death by controlling the activity of Caspase3.
본 발명에 있어서, 상기 메테오린-유사체는 정상 세포의 세포 사멸을 유도하지 않는 것을 특징으로 할 수 있다.In the present invention, the meteorin-analog does not induce apoptosis of normal cells.
본 발명에 있어서, 약학적 조성물의 투여 경로는 이들로 한정되는 것은 아니지만 구강, 정맥내, 근육내, 동맥내, 골수내, 경막내, 심장내, 경피, 피하, 복강내, 비강내, 장관, 국소, 설하 또는 직장이 포함된다.In the present invention, the route of administration of the pharmaceutical composition may be, but not limited to, oral, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, Topical, sublingual, or rectal.
본 발명의 조성물은 경구 또는 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식을 선택하는 것이 바람직하며, 이에 한정되는 것은 아니다.The composition of the present invention may be administered orally or parenterally, and it is preferable to select parenterally when injecting parenterally or intraperitoneally, intramuscularly, subcutaneously, intravenously, intramuscularly or intrasternally , But is not limited thereto.
본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 상기 조성물은 1일 0.0001~1g/으로, 바람직하게는 0.001~200/으로 투여하는 것이 바람직하나 이에 한정되지 않는다. 상기 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition is preferably administered at a dose of 0.0001 to 1 g / day, preferably 0.001 to 200 / day, but is not limited thereto. The above administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propyleneglycol), 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로 제라틴 등이 사용될 수 있다.
In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Propyleneglycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. Examples of the suppository base include witepsol, macrogol,
본 발명은 다른 관점에서, 서열번호 1의 아미노산 서열로 표시되는 메테오린-유사체를 유효성분으로 함유하는 유방암, 대장암, 및 자궁경부암으로 구성된 군에서 선택되는 암의 예방 또는 개선용 건강기능식품에 관한 것이다.In another aspect, the present invention relates to a health functional food for preventing or ameliorating cancer selected from the group consisting of breast cancer, colon cancer, and cervical cancer containing the meteorin-analogue represented by the amino acid sequence of SEQ ID NO: 1 as an active ingredient .
본 명세서에서 용어, "개선"이란 증상의 예방, 개선, 치료 또는 이러한 증상의 발현 지연을 포함하는 의미이다.As used herein, the term "improvement" is meant to include preventing, ameliorating, treating, or delaying the onset of such symptoms.
본 명세서에서 용어 "기능식품"은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.As used herein, the term " functional food "means a food prepared or processed using a raw material or ingredient having functionality useful to the human body according to Law No. 6727 on health functional foods, and" function " And function of the nutrient for the purpose of obtaining a beneficial effect in health use such as controlling the nutrient or physiological action.
본 발명의 건강식품은 상기 메테오린-유사체를 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다.The health food of the present invention can be used as it is, or can be used with other food or food ingredients, and can be suitably used according to conventional methods.
상기 식품의 종류에는 특별한 제한은 없다. 상기 식품의 예로는 드링크제, 육류, 소세지, 빵, 비스켓, 떡, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of the food. Examples of the food include dairy products including drinks, meat, sausage, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, ice cream, various soups, And a combination thereof, all of which include health foods in a conventional sense.
본 발명에 따른 메테오린-유사체는 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 메테오린-유사체의 양은 전체 식품중량의 0.01 내지 15중량%로 가할 수 있으며, 건강 음료 조성물은 100를 기준으로 0.02 내지 5g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The meteorin-analogs according to the present invention can be added directly to food or used with other food or food ingredients, and can be suitably used according to conventional methods. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose (for prevention or improvement). In general, the amount of the meteorin-analog in the health food may be from 0.01 to 15% by weight of the total food, and the health beverage composition may be added in a proportion of from 0.02 to 5 g, preferably from 0.3 to 1 g, have. However, in the case of long-term consumption intended for health or hygiene purposes or for health control purposes, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 메테오린-유사체를 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다.The health functional beverage composition of the present invention is not particularly limited to the ingredients other than the above-mentioned ingredients containing the meteorin-analog as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above .
상기 외에 본 발명의 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다.
In addition to the above-mentioned foods, the food of the present invention may contain flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이들 실시예에 의해 제한되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are for illustrative purposes only and that the scope of the present invention is not limited by these embodiments.
실시예 1: 메테오린-유사체의 유방암 세포 사멸 유도 확인Example 1: Confirmation of the induction of death of mammalian cells by methorein-analog
(1) Annexin V와 MTT 분석을 통한 세포 사멸 측정(1) Measurement of apoptosis through Annexin V and MTT assay
메테오린-유사체 (R & D System, USA)의 유방암 세포에 대한 세포 사멸 효과를 두 가지 방법으로 확인하였다. 첫 번째, 유방암 세포주 (MDA-MB231, American Type Culture Collection (ATCC))에 메테오린-유사체를 처리하고 Annexin V (Sigma-Aldrich)의 형광을 현미경하에서 조사하여, Annexin V-양성 죽은 세포와 Annexin V-음성 살아있는 세포의 수를 측정하였다. 세포에 30 ng/ml의 메테오린-유사체를 48 시간 동안 처리하고 측정한 결과, 살아있는 세포의 수는 감소하고 죽은 세포의 수는 증가한다는 것을 확인할 수 있었다 (도 1A). 두 번째, 세포에 메테오린-유사체를 처리하고 MTT 분석 (Sigma-Aldrich)하였다. 세포에 농도 0 ng/ml, 10 ng/ml, 30 ng/ml, 100 ng/ml의 메테오린-유사체를 처리한 후 MTT 분석을 한 결과, 농도가 증가함에 따라 세포생존율이 감소되는 것을 확인할 수 있었다 (도 1B와 도 2).Meteorin-like (R & D System, USA) cell death killing effect on breast cancer cells was confirmed by two methods. First, mammalian cell lines (MDA-MB231, American Type Culture Collection (ATCC)) were treated with meteorin-analog and the fluorescence of Annexin V (Sigma-Aldrich) was examined under a microscope to determine the presence of Annexin V- The number of viable cells was measured. The cells were treated with 30 ng / ml of the methorein-analog for 48 hours and the results showed that the number of living cells decreased and the number of dead cells increased (FIG. 1A). Second, the cells were treated with meteorin-analog and MTT assay (Sigma-Aldrich). MTT analysis of cells treated with 0 ng / ml, 10 ng / ml, 30 ng / ml, and 100 ng / ml of meteorin-analogs resulted in a decrease in cell viability (Fig. 1B and Fig. 2).
(2) 세포 사멸에 관여하는 단백질인 Caspase3의 발현과 활성 측정(2) Expression and activity measurement of
세포 사멸에 관여하는 단백질인 caspase3 (Cell Signaling Technology)의 발현과 활성을 유방암 세포주에서 측정하였다. caspase3의 발현은 유방암 세포주 (MDA-MB231)에 30 ng/ml의 메테오린-유사체를 12 시간 또는 24 시간 처리한 후 웨스턴블로팅 (Western blotting)으로 분석하였다. 그 결과, 24 시간 처리하였을 경우, caspase3의 발현이 강하게 유도되는 것을 확인할 수 있었다 (도 3). caspase3의 활성을 세포에 100 ng/ml의 메테오린-유사체를 처리한 후 측정한 결과, 그 활성 역시 증가되는 것을 확인할 수 있었다 (도 1B). Expression and activity of caspase3 (Cell Signaling Technology), a protein involved in apoptosis, were measured in breast cancer cell lines. Expression of
종합하면, 메테오린-유사체는 유방암 세포주에서 caspase-3 의존적으로 세포 사멸 효과를 보인다는 것을 알 수 있었다.
Taken together, it was found that the meteorin-analogs had caspase-3-dependent apoptosis in breast cancer cell lines.
실시예 2: 메테오린-유사체의 유방암 세포 증식 억제 확인Example 2: Confirmation of inhibition of breast cancer cell proliferation of methorein-analog
메테오린-유사체가 유방암 세포의 세포 증식을 조절하는지 알아보기 위하여 세포주기 분석을 수행하였다. 먼저. 유방암 세포주 (MDA-MB231)에 30 ng/ml 메테오린-유사체를 48 시간 처리한 후 형광이용세포분류기 (FACS, Fluorescence-activated cell sorter, Canto II)를 이용하여 세포주기를 분석하였다. 그 결과, 세포주기 중 G1 기에 있는 세포가 대조군에서는 66%이나, 메테오린-유사체 처리군에서는 76%로 증가된 것으로 확인되어 메테오린-유사체가 G1 정지를 일으킨다는 것을 확인할 수 있었다 (도 4). 다음으로, 세포주기 조절에 관여하는, 특히, G1 정지에 관여하는 단백질인 p21 (Cell Signaling Technology)의 발현을 측정하였다. 세포에 30 ng/ml 메테오린-유사체를 0, 3, 6, 12, 24, 48 시간 처리한 후 p21의 발현을 웨스턴블로팅으로 측정하였다. 그 결과, 메테오린-유사체를 처리하고 3시간 이후부터 발현이 증가하여 48 시간까지 지속되는 것으로 나타났다 (도 4). 이 결과는 메테오린-유사체가 유방암 세포의 G1 정지를 유도하여 세포 증식을 억제한다는 것을 확인시켜준다.
Cell cycle analysis was performed to determine whether meteorin-analogs regulate cell proliferation in breast cancer cells. first. The cell cycle was analyzed using a 30 ng / ml meteorin-analogue for breast cancer cell line (MDA-MB231) for 48 hours and then using a fluorescence-activated cell sorter (FACS). As a result, it was confirmed that the cells in the G1 phase of the cell cycle were increased to 66% in the control group and 76% in the treatment with the meteorin-analog group, indicating that the meteorin-analog causes G1 arrest (FIG. 4) . Next, the expression of p21 (Cell Signaling Technology), which is involved in cell cycle regulation, in particular, a protein involved in G1 arrest, was measured. Cells were treated with 30 ng / ml Meteorin-analog for 0, 3, 6, 12, 24, 48 hours and the expression of p21 was measured by Western blotting. As a result, the expression of methorein-analog was increased after 3 hours and continued until 48 hours (FIG. 4). This result confirms that the meteorin-analog induces G1 arrest in breast cancer cells and inhibits cell proliferation.
실시예 3: 메테오린-유사체의 정상 세포에 대한 세포 사멸 효과 측정Example 3: Measurement of cytotoxic effect of meteorin-analog on normal cells
메테오린-유사체가 정상 세포에 대한 세포 사멸 효과를 보이는지 알아보기 위하여 정상 유방 세포주 (MCF-10A, ATCC)에 메테오린-유사체를 처리하고 세포생존율을 측정하였다. 메테오린-유사체를 농도 0 ng/ml, 50 ng/ml, 200 ng/ml, 500 ng/ml로하여 정상 유방 세포주 (MCF-10A)에 처리하였다. 그 결과, 유방암 세포주 (MDA-MB231)에서는 농도 증가에 따라 세포생존율이 감소되는 것에 비해 정상 유방 세포주 (MDA-MB231)에서는 세포생존율의 감소가 없는 것을 확인할 수 있었다 (도 5).
In order to investigate whether the meteorin-analogue has apoptotic effect on normal cells, the normal breast cell line (MCF-10A, ATCC) was treated with meteorin-analog and cell viability was measured. (MCF-10A) at a concentration of 0 ng / ml, 50 ng / ml, 200 ng / ml and 500 ng / ml. As a result, it was confirmed that the cell survival rate was decreased according to the concentration increase in the breast cancer cell line (MDA-MB231), while the cell survival rate was not decreased in the normal breast cell line (MDA-MB231) (FIG.
실시예 4: 메테오린-유사체의 대장암, 자궁경부암 및 췌장암 세포 사멸 유도 효과 확인Example 4: Confirmation of inducing effect of methelin-analog on colon cancer, cervical cancer and pancreatic cancer cell death
메테오린-유사체의 대장암, 자궁경부암 및 췌장암에 대한 세포 사멸 효과를 확인하였다. 대장암 세포주 (HT-29, ATCC), 자궁경부암 세포주 (HeLa, ATCC) 및 췌장암 세포주 (Mia PaCa-2, American Type Culture Collection (ATCC))에 메테오린-유사체를 각각 처리하고 MTT 분석하였다. 각 세포에 500 ng/ml의 메테오린-유사체를 처리한 후 MTT 분석을 한 결과, 세포생존율이 대장암 세포주의 경우 40%, 자궁경부암 세포주와 췌장암 세포주의 경우 각각 30% 감소되는 것을 확인할 수 있었다 (도 6과 도 7A). 이 결과는 메테오린-유사체가 유방암뿐만 아니라 대장암, 자궁경부암 및 췌장암에도 세포 사멸 효과를 보일 수 있음을 의미한다.
The cytotoxic effect of meteorin-analogs on colon cancer, cervical cancer and pancreatic cancer was confirmed. METHODS: Methylorine-analogs were treated and MTT assayed in colon cancer cell line (HT-29, ATCC), cervical cancer cell line (HeLa, ATCC) and pancreatic cancer cell line (Mia PaCa-2, American Type Culture Collection (ATCC)). MTT analysis after treatment of each cell with 500 ng / ml of meteorin-analog showed that cell survival was reduced by 40% in colon cancer cell line and by 30% in cervical cancer cell line and pancreatic cancer cell line, respectively (Figs. 6 and 7A). This result implies that the meteorin-analog can show apoptotic effects not only in breast cancer but also in colorectal cancer, cervical cancer and pancreatic cancer.
실시예 5: 메테오린-유사체의 신경암 및 난소암 세포에 대한 세포 사멸 효과 조사Example 5: Investigation of apoptotic effect of meteorin-analog on neuronal and ovarian cancer cells
메테오린-유사체의 신경암 및 난소암에 대한 세포 사멸 효과를 조사하였다. 신경암 세포주 (SH-SY5Y, American Type Culture Collection, ATCC) 및 난소암 세포주 (SKOV3, American Type Culture Collection, ATCC)에 메테오린-유사체를 각각 처리하고 MTT 분석하였다. 각 세포에 50 ng/ml, 200 ng/ml 및 500 ng/ml의 메테오린-유사체를 처리한 후 MTT 분석을 하였으나, 세포사가 유도되는 것을 확인할 수 없었다 (도 7A와 7B). 이 결과는 메테오린-유사체가 모든 암종에서 생존억제 효과를 나타내는 것은 아니라는 것을 의미한다.
Meteorin-analogues were examined for neuronal and ovarian cancer cell killing effect. Methylorine-analogs were treated and MTT assayed on neuronal cell line (SH-SY5Y, American Type Culture Collection, ATCC) and ovarian cancer cell line (SKOV3, American Type Culture Collection, Each cell was treated with 50 ng / ml, 200 ng / ml and 500 ng / ml of meteorin-analog, and MTT analysis was performed, but it was not confirmed that cell death was induced (Figs. 7A and 7B). This result implies that the meteorin-analog does not have a survival-inhibiting effect in all carcinomas.
실시예 6: 마우스 메테오린-유사체와 인간 메테오린-유사체의 아미노산 서열과 세포사 유도 효과 비교Example 6: Comparison of the amino acid sequence of mouse meteorin-analog and human meteorin-analog with the cell death inducing effect
실시예 1에서 실시예 5에 사용된 메테오린-유사체는 인간 메테오린-유사체이다. 인간 메테오린-유사체의 암세포 사멸 효과의 정도를 다른 종의 메테오린-유사체와 비교하기 위하여, 마우스 메테오린-유사체의 아미노산 서열을 조사하고 마우스 메테오린-유사체에 의한 유방암 세포주의 세포생존율을 측정하였다. 마우스 메테오린-유사체 (R & D System, USA)는 인간 메테오린-유사체와 265개의 아미노산 일치하여 79%의 상동성을 보였다. 세포 사멸 유도 효과를 측정한 결과에서는, 인간 메테오린-유사체가 유방암 세포주의 세포생존율을 40% 감소시키는데 비해, 마우스 메테오린-유사체는 25% 감소시키는 것에 그치는 것을 알 수 있었다 (도 8). 이 결과는 두 단백질 간의 아미노산 서열상 21% 상이성에 근거하여 나타났으며, 인간 메테오린-유사체가 마우스 메테오린-유사체보다 유방암을 억제하는 능력이 뛰어남을 의미한다.
The meteorin-analog used in Example 5 in Example 1 is a human meteorin-analog. In order to compare the degree of cancer cytotoxic effect of human meteorin-analog with that of other species, the amino acid sequence of mouse meteorin-analog was examined and the cell survival rate of breast cancer cell line by mouse meteorin-analog was measured . The mouse meteorin-analog (R & D System, USA) showed homology of 79% with 265 amino acids consistent with human methorein-analog. As a result of measuring the cell death-inducing effect, it was found that the human meteorin-analog decreased the cell survival rate of the breast cancer cell line by 40%, while the mouse meteorin-analog decreased by 25% (FIG. 8). This result was based on 21% amino acid sequence identity between the two proteins, indicating that the human methone - 1 - analog is more capable of inhibiting breast cancer than the mouse meteorin - analog.
실시예 7: 메테오린과 메테오린-유사체의 세포사 유도 및 세포 증식 효과 비교Example 7: Comparison of cell death induction and cell proliferation effect of meteorin and meteorin-analog
유방암 세포주 (MDA-MB231)에 메테오린 (CUSABIO) 또는 메테오린-유사체를 각각 농도별 (0, 50, 200, 500 ng/ml)로 처리한 후 생존율을 비교해보았다. 메테오린의 경우 500 ng/ml 농도에서 대조군에 비해 약 70%로 생존율이 감소하지만, 메테오린-유사체는 같은 농도에서 세포생존율이 약 50% 까지 감소하였다 (도 9A). 이는 메테오린-유사체가 메테오린보다 암 세포 억제 능력이 우수함을 보여주는 것이다. 또한 메테오린과 메테오린-유사체를 농도별로 처리 후 세포주기억제 단백질인 p21의 발현을 비교해봤을 때도, 메테오린에 의한 증가보다, 메테오린-유사체에 의해 더욱 뚜렷이 증가하였다 (도 9B). 이 역시 메테오린 유사체가 메테오린보다 세포주기 억제 효과가 뛰어남을 의미한다.
The survival rates of metanephrine or meteorin-analogs were measured by MDA-MB231 (0, 50, 200, 500 ng / ml) In the case of meteorin, the survival rate was reduced to about 70% compared to the control at the concentration of 500 ng / ml, but the meteorin-analog decreased cell viability by about 50% at the same concentration (Fig. 9A). This demonstrates that the meteorin-analog is superior to methorein in its ability to inhibit cancer cells. In addition, the expression of p21, a cell cycle arresting protein after treatment with meteorin and meteorin-analogs at different concentrations, was more markedly increased by the meteorin-analog than by the increase by meteorin (Fig. 9B). This also means that the meteorin analogue is superior to the methionine inhibitor in the cell cycle.
이상으로 본 발명 내용을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일뿐이며, 이에 의한 본 발명의 범위가 제한 되는것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의해 정의 된다고 할 것이다.Having thus described the present invention in detail, it will be apparent to those skilled in the art that the specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereto . Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.
<110> Korea University Research and Business Foundation <120> Composition for preventing or treating cancer containing METRNL (meteorin-like) <130> P15-B257 <160> 1 <170> KopatentIn 2.0 <210> 1 <211> 311 <212> PRT <213> Homo sapiens <400> 1 Met Arg Gly Ala Ala Arg Ala Ala Trp Gly Arg Ala Gly Gln Pro Trp 1 5 10 15 Pro Arg Pro Pro Ala Pro Gly Pro Pro Pro Pro Pro Leu Pro Leu Leu 20 25 30 Leu Leu Leu Leu Ala Gly Leu Leu Gly Gly Ala Gly Ala Gln Tyr Ser 35 40 45 Ser Asp Arg Cys Ser Trp Lys Gly Ser Gly Leu Thr His Glu Ala His 50 55 60 Arg Lys Glu Val Glu Gln Val Tyr Leu Arg Cys Ala Ala Gly Ala Val 65 70 75 80 Glu Trp Met Tyr Pro Thr Gly Ala Leu Ile Val Asn Leu Arg Pro Asn 85 90 95 Thr Phe Ser Pro Ala Arg His Leu Thr Val Cys Ile Arg Ser Phe Thr 100 105 110 Asp Ser Ser Gly Ala Asn Ile Tyr Leu Glu Lys Thr Gly Glu Leu Arg 115 120 125 Leu Leu Val Pro Asp Gly Asp Gly Arg Pro Gly Arg Val Gln Cys Phe 130 135 140 Gly Leu Glu Gln Gly Gly Leu Phe Val Glu Ala Thr Pro Gln Gln Asp 145 150 155 160 Ile Gly Arg Arg Thr Thr Gly Phe Gln Tyr Glu Leu Val Arg Arg His 165 170 175 Arg Ala Ser Asp Leu His Glu Leu Ser Ala Pro Cys Arg Pro Cys Ser 180 185 190 Asp Thr Glu Val Leu Leu Ala Val Cys Thr Ser Asp Phe Ala Val Arg 195 200 205 Gly Ser Ile Gln Gln Val Thr His Glu Pro Glu Arg Gln Asp Ser Ala 210 215 220 Ile His Leu Arg Val Ser Arg Leu Tyr Arg Gln Lys Ser Arg Val Phe 225 230 235 240 Glu Pro Val Pro Glu Gly Asp Gly His Trp Gln Gly Arg Val Arg Thr 245 250 255 Leu Leu Glu Cys Gly Val Arg Pro Gly His Gly Asp Phe Leu Phe Thr 260 265 270 Gly His Met His Phe Gly Glu Ala Arg Leu Gly Cys Ala Pro Arg Phe 275 280 285 Lys Asp Phe Gln Arg Met Tyr Arg Asp Ala Gln Glu Arg Gly Leu Asn 290 295 300 Pro Cys Glu Val Gly Thr Asp 305 310 <110> Korea University Research and Business Foundation <120> Composition for preventing or treating cancer containing METRNL meteorin- <130> P15-B257 <160> 1 <170> Kopatentin 2.0 <210> 1 <211> 311 <212> PRT <213> Homo sapiens <400> 1 Met Arg Gly Ala Ala Arg Ala Ala Trp Gly Arg Ala Gly Gln Pro Trp 1 5 10 15 Pro Arg Pro Pro Ala Pro Gly Pro Pro Pro Pro Pro Leu Pro Leu Leu 20 25 30 Leu Leu Leu Leu Ala Gly Leu Leu Gly Aly Gly Aly Gly Aly Gly Tyr Ser 35 40 45 Ser Asp Arg Cys Ser Trp Lys Gly Ser Gly Leu Thr His Glu Ala His 50 55 60 Arg Lys Glu Val Glu Gln Val Tyr Leu Arg Cys Ala Ala Gly Ala Val 65 70 75 80 Glu Trp Met Tyr Pro Thr Gly Ala Leu Ile Val Asn Leu Arg Pro Asn 85 90 95 Thr Phe Ser Pro Ala Arg His Leu Thr Val Cys Ile Arg Ser Phe Thr 100 105 110 Asp Ser Ser Gly Ala Asn Ile Tyr Leu Glu Lys Thr Gly Glu Leu Arg 115 120 125 Leu Leu Val Pro Asp Gly Asp Gly Arg Pro Gly Arg Val Gln Cys Phe 130 135 140 Gly Leu Glu Gln Gly Gly Leu Phe Val Glu Ala Thr Pro Gln Gln Asp 145 150 155 160 Ile Gly Arg Arg Thr Thr Gly Phe Gln Tyr Glu Leu Val Arg Arg His 165 170 175 Arg Ala Ser Asp Leu His Glu Leu Ser Ala Pro Cys Arg Pro Cys Ser 180 185 190 Asp Thr Glu Val Leu Leu Ala Val Cys Thr Ser Asp Phe Ala Val Arg 195 200 205 Gly Ser Ile Gln Gln Val Thr His Glu Pro Glu Arg Gln Asp Ser Ala 210 215 220 Ile His Leu Arg Val Ser Ser Leu Tyr Arg Gln Lys Ser Arg Val Phe 225 230 235 240 Glu Pro Val Pro Glu Gly Asp Gly His Trp Gln Gly Arg Val Val Arg Thr 245 250 255 Leu Leu Glu Cys Gly Val Arg Pro Gly His Gly Asp Phe Leu Phe Thr 260 265 270 Gly His Met His Phe Gly Glu Ala Arg Leu Gly Cys Ala Pro Arg Phe 275 280 285 Lys Asp Phe Gln Arg Met Tyr Arg Asp Ala Gln Glu Arg Gly Leu Asn 290 295 300 Pro Cys Glu Val Gly Thr Asp 305 310
Claims (5)
A pharmaceutical composition for preventing or treating cancer, which comprises a meteorin-analogue represented by the amino acid sequence of SEQ ID NO: 1 as an active ingredient, selected from the group consisting of breast cancer, colon cancer, and cervical cancer.
The pharmaceutical composition according to claim 1, wherein the methorein-analog inhibits cancer cell proliferation or induces cancer cell death.
The pharmaceutical composition for preventing or treating cancer according to claim 1, wherein the meteorin-analog modulates p21 protein activity to inhibit cancer cell proliferation or induce cancer cell death through an increase in Caspase3 expression.
The pharmaceutical composition according to claim 1, wherein the meteorin-analog does not induce apoptosis of normal cells.
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| US20130267464A1 (en) * | 2008-07-24 | 2013-10-10 | Nsgene A/S | Therapeutic use of a growth factor, metrnl |
| WO2015003254A1 (en) * | 2013-07-11 | 2015-01-15 | Exerkine Corporation | Therapeutic method of inducing mitochondrial biogenesis |
| CN104808004A (en) * | 2015-05-06 | 2015-07-29 | 中国人民解放军第二军医大学 | Application of METRNL protein as colon cancer diagnostic marker and kit |
| US20150322460A1 (en) * | 2013-01-25 | 2015-11-12 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for regulating thermogenesis and muscle inflammation using metrnl and metrn |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130267464A1 (en) * | 2008-07-24 | 2013-10-10 | Nsgene A/S | Therapeutic use of a growth factor, metrnl |
| US20150322460A1 (en) * | 2013-01-25 | 2015-11-12 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for regulating thermogenesis and muscle inflammation using metrnl and metrn |
| WO2015003254A1 (en) * | 2013-07-11 | 2015-01-15 | Exerkine Corporation | Therapeutic method of inducing mitochondrial biogenesis |
| CN104808004A (en) * | 2015-05-06 | 2015-07-29 | 中国人民解放军第二军医大学 | Application of METRNL protein as colon cancer diagnostic marker and kit |
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