JPH02240019A - Anti-carcinogenic promoter - Google Patents
Anti-carcinogenic promoterInfo
- Publication number
- JPH02240019A JPH02240019A JP1060535A JP6053589A JPH02240019A JP H02240019 A JPH02240019 A JP H02240019A JP 1060535 A JP1060535 A JP 1060535A JP 6053589 A JP6053589 A JP 6053589A JP H02240019 A JPH02240019 A JP H02240019A
- Authority
- JP
- Japan
- Prior art keywords
- monolinolein
- alpha
- carcinogenic
- oil
- carcinogenic promoter
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 230000003217 anti-cancerogenic effect Effects 0.000 title claims abstract description 14
- WECGLUPZRHILCT-GSNKCQISSA-N 1-linoleoyl-sn-glycerol Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@@H](O)CO WECGLUPZRHILCT-GSNKCQISSA-N 0.000 claims abstract description 24
- 239000004480 active ingredient Substances 0.000 claims abstract description 8
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 abstract description 16
- 208000005623 Carcinogenesis Diseases 0.000 abstract description 11
- 230000036952 cancer formation Effects 0.000 abstract description 11
- 231100000504 carcinogenesis Toxicity 0.000 abstract description 11
- 241000701044 Human gammaherpesvirus 4 Species 0.000 abstract description 8
- 230000000711 cancerogenic effect Effects 0.000 abstract description 6
- 231100000315 carcinogenic Toxicity 0.000 abstract description 6
- 239000003921 oil Substances 0.000 abstract description 6
- 235000019198 oils Nutrition 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 abstract description 4
- 102000004190 Enzymes Human genes 0.000 abstract description 2
- 108090000790 Enzymes Proteins 0.000 abstract description 2
- 239000003377 acid catalyst Substances 0.000 abstract description 2
- 239000000427 antigen Substances 0.000 abstract description 2
- 102000036639 antigens Human genes 0.000 abstract description 2
- 108091007433 antigens Proteins 0.000 abstract description 2
- 239000003443 antiviral agent Substances 0.000 abstract description 2
- 230000032050 esterification Effects 0.000 abstract description 2
- 238000005886 esterification reaction Methods 0.000 abstract description 2
- 235000013376 functional food Nutrition 0.000 abstract description 2
- 235000011187 glycerol Nutrition 0.000 abstract description 2
- 230000007062 hydrolysis Effects 0.000 abstract description 2
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 abstract description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 abstract description 2
- 239000008158 vegetable oil Substances 0.000 abstract description 2
- 235000007354 Coix lacryma jobi Nutrition 0.000 abstract 1
- 244000077995 Coix lacryma jobi Species 0.000 abstract 1
- 229920000742 Cotton Polymers 0.000 abstract 1
- 230000003327 cancerostatic effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 150000002148 esters Chemical group 0.000 abstract 1
- 235000001497 healthy food Nutrition 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- 235000012424 soybean oil Nutrition 0.000 abstract 1
- 239000003549 soybean oil Substances 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 206010028980 Neoplasm Diseases 0.000 description 11
- ARSRBNBHOADGJU-UHFFFAOYSA-N 7,12-dimethyltetraphene Chemical compound C1=CC2=CC=CC=C2C2=C1C(C)=C(C=CC=C1)C1=C2C ARSRBNBHOADGJU-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 5
- USPSDZQQNLMVMK-UHFFFAOYSA-N 1-Monolinolein Natural products CCCCCC=CC=CCCCCCCCC(=O)OCC(O)CO USPSDZQQNLMVMK-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241000700605 Viruses Species 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000003999 initiator Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004734 cutaneous carcinogenesis Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241000701076 Macacine alphaherpesvirus 1 Species 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 235000009074 Phytolacca americana Nutrition 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 240000005578 Rivina humilis Species 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000001973 epigenetic effect Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229940074096 monoolein Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- HCZKYJDFEPMADG-UHFFFAOYSA-N nordihydroguaiaretic acid Chemical compound C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
- 235000015145 nougat Nutrition 0.000 description 1
- 231100000590 oncogenic Toxicity 0.000 description 1
- 230000002246 oncogenic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 230000004095 viral genome expression Effects 0.000 description 1
Landscapes
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【発明の詳細な説明】
(産業上の利用分野)
本発明は発癌の予防の目的で利用される抗発癌プロモー
ターに関する。DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to an anti-carcinogenic promoter used for the purpose of preventing carcinogenesis.
(従来技術及び解決すべき問題点)
発癌機構として一般に受け入れられている発癌二段階説
は正常細胞の染色体に障害を与えるイニシエーターと、
その障害を受けて潜在的腫瘍細胞に変化した細胞に後成
効果を与えて腫瘍細胞に変化させるプロモーターとの働
きにより腫瘍を生じる実験系に基づいている。(Prior art and problems to be solved) The two-stage theory of carcinogenesis, which is generally accepted as a carcinogenic mechanism, is that an initiator damages the chromosomes of normal cells;
It is based on an experimental system that generates tumors through the action of promoters that exert an epigenetic effect on cells that have undergone this disorder and have turned into potential tumor cells, transforming them into tumor cells.
イニシエーターとしてはDMBA(ジメチルベンズアン
トラセン)等が、プロモーターとしてはTPA(テトラ
デカノイルホルボールアセテート)等がそれぞれ代表的
なものとして知られている。そして、こういったプロモ
ーター,イニシエーターを用いる発癌実験を通して発癌
の機構を明らかにしていこうとする研究が進められてい
る。DMBA (dimethylbenzanthracene) and the like are known as typical initiators, and TPA (tetradecanoylphorbol acetate) and the like are known as promoters. Research is underway to clarify the mechanism of carcinogenesis through carcinogenesis experiments using these promoters and initiators.
特にプロモーターによって引き起こされるプロモーショ
ンの過程はガン遺伝子の普遍性とあいまって重要視され
ており、この点を明らかにすることによって新しい制ガ
ン性の概念を導き出そうとする試みは多い。その一つが
発癌プロモーターの作用を阻害する抗発癌プロモーター
の探索であり、これまでにNDGA(ノルジヒドログア
イアレチックアシッド)等のりポキシゲナーゼ阻害剤や
W−7のようなカルモジュリン阻害剤,グルココルチコ
イド,レチノイド等が知られているがこのようなインヒ
ビターの探索はまだ遅れた領域である。In particular, the process of promotion caused by promoters is considered important in conjunction with the universality of oncogenes, and there are many attempts to derive new concepts of anticancer properties by clarifying this point. One of these is the search for anti-carcinogenic promoters that inhibit the action of oncogenic promoters, and so far we have used glue poxygenase inhibitors such as NDGA (nordihydroguaiaretic acid), calmodulin inhibitors such as W-7, glucocorticoids, and retinoids. However, the search for such inhibitors is still in an underdeveloped area.
また、天然から抗発癌プロモーター.を探索する試みも
盛んに行われており、植物の粗抽出物が実験的発癌を抑
制することも知られているが、その有効成分が明らかに
なっている例は少ない。It is also a naturally occurring anti-carcinogenic promoter. Many attempts have been made to explore the potential of carcinogenesis, and crude plant extracts are known to inhibit experimental carcinogenesis, but there are few examples of their active ingredients being clarified.
本発明において解決すべき課題は、植物界より発癌プロ
モーション阻害作用を有する化合物(抗発癌プロモータ
ー)を見い出し、該化合物を有効成分とする発癌プロモ
ーション阻害剤を提供することにある。The problem to be solved by the present invention is to discover a compound (anti-carcinogenic promoter) from the plant kingdom that has a carcinogenic promotion inhibiting effect, and to provide a carcinogenic promotion inhibitor containing this compound as an active ingredient.
(課題を解決するための手段)
本発明者等はEBV(エプスタイン・バール・ウィルス
)のゲノムを内蔵するパーキット・リンパ腫由来の培養
細胞であるRaji(ラジ)株において、EBV・ゲノ
ムの発現を阻害する化合物の多くが、マウス皮膚発癌二
段階実験において抗発癌プロモーターとして作用を示す
点に着目し、植物中に含まれる成分の中からEBV・ゲ
ノムの発現を阻害するウィルス・ゲノム不活化物質を探
索したEBウィルス・ゲノムの発現阻害作用は下記のよ
うな方法で観察する。(Means for Solving the Problem) The present inventors inhibited the expression of the EBV (Epstein-Barr virus) genome in the Raji strain, which is a cultured cell derived from Purkitt's lymphoma and contains the EBV (Epstein-Barr virus) genome. Focusing on the fact that many of the compounds shown to act as anti-carcinogenic promoters in a two-stage mouse skin carcinogenesis experiment, we searched for virus/genome inactivating substances that inhibit EBV/genome expression among components contained in plants. The inhibitory effect on the expression of the EB virus genome is observed by the following method.
すなわち、前述のRaji株培養系に発癌プロモーター
であるTPAと活性発現のために相乗作用として働くn
一酪酸,それに、被験物質を加え培養し、TPAにより
活性化されて細胞表面上に発現されるEBV−EA(E
B・ウィルスー早期抗原)を上咽頭癌患者血清由来の抗
体を用いる間接蛍光抗体法で検出する方法である。That is, in the Raji strain culture system mentioned above, n, which acts synergistically with TPA, a carcinogenic promoter, to express activity.
Monobutyric acid and the test substance were added and cultured, and EBV-EA (EBV-EA), which is activated by TPA and expressed on the cell surface, was cultured.
This is a method for detecting B. virus (early antigen) using an indirect fluorescent antibody method using antibodies derived from serum from patients with nasopharyngeal cancer.
具体的には、EBV潜在感染ヒトリンパ芽球様細胞株R
aji細胞の培養液としてRPMI 1640に胎仔血
清及び抗生物質を加えたものを使用する。Specifically, EBV latently infected human lymphoblastoid cell line R
RPMI 1640 with fetal serum and antibiotics added is used as a culture medium for aji cells.
この培養条件下で、EBV−E.’l.自然発現率は0
.1%以下である。I X 106細胞/mlの濃度に
調整したRaji細胞を、4mMのn一酪酸,20ng
/mlのTPA,それにTPAに対し例えば50倍モル
のα−モノリノレインを加えた上記培養液中で37°C
,48時間培養する。上咽頭癌患者血清を用いた間接蛍
光抗体法にてEBV−EAを染色し、陽性細胞の率をα
−モノリノレインを加えなかなコントロールに対し算出
し、ウイルス・ゲノムの発現阻害活性とする。Under this culture condition, EBV-E. 'l. Natural occurrence rate is 0
.. It is less than 1%. Raji cells adjusted to a concentration of I x 106 cells/ml were treated with 4mM n-monobutyric acid, 20ng
/ml of TPA and 50 times the molar amount of α-monolinolein to TPA in the above culture solution at 37°C.
, incubate for 48 hours. EBV-EA was stained using indirect fluorescent antibody method using nasopharyngeal cancer patient serum, and the percentage of positive cells was determined by α.
- Calculated against the control without monolinolein added and used as the viral genome expression inhibition activity.
α−モノリノレインのウィルス・ゲノムの発現阻害活性
は100%となる。The virus genome expression inhibition activity of α-monolinolein is 100%.
このように本発明のα−モノリノレインはTPAによる
EBV−EAの発言を顕著に阻害することから、抗発癌
プロモーターとしての作用が期待できる。As described above, since the α-monolinolein of the present invention significantly inhibits the expression of EBV-EA by TPA, it can be expected to act as an anti-carcinogenic promoter.
α−モノリノレインの発癌プロモーション阻害作用はマ
ウス皮膚発癌二段階実験により明確に示すことができ、
具体的には下記の方法で行う。The inhibitory effect of α-monolinolein on carcinogenesis can be clearly demonstrated through a two-step mouse skin carcinogenesis experiment.
Specifically, the following method is used.
まず、発癌プロモーション作用はマウスの背部皮膚に7
,12−ジメチルベンズアントラセン(DMBA)を1
回だけ塗布してインシエートし、1週間後よりTPAを
週に2回塗布することによりプロモーション活性を調べ
る。First, the carcinogenesis promoting effect was found in the dorsal skin of mice.
, 12-dimethylbenzanthracene (DMBA)
After one week, promotion activity is examined by applying TPA twice a week.
一方、発癌プロモーション阻害作用を調べるには、TP
Aを塗布する1時間前に、被検化合物を塗布し、上記の
TPA塗布のみのコントロールのプロモーション活性と
比較検討する。On the other hand, in order to investigate the inhibitory effect on carcinogenesis promotion, TP
One hour before applying A, the test compound is applied and compared with the promotion activity of the control with only TPA applied.
プロモーション活性は腫瘍を有するマウスの比率とマウ
スー匹当たりの腫瘍の数の平均値で評価する。Promotional activity is evaluated by the proportion of mice bearing tumors and the average number of tumors per mouse.
例えばα−モノリノレインの場合には、DMBA+TP
A群が8週以後で100%の腫瘍発生頻度に達するのに
対しα−モノリノレインを前処理したDMBA+α−モ
ノリノレイン+TPA群の腫瘍発生頻度は11週目でも
40%であった。また、マウスー匹当たりの平均腫瘍個
数で比較するとDMBA+TPA群が13週目で4.8
個であるのに対し、DMBA十〇−モノリノレイン+T
PA群は、2.7個であった。For example, in the case of α-monolinolein, DMBA+TP
While group A reached a tumor incidence of 100% after 8 weeks, the tumor incidence in the DMBA+α-monolinolein+TPA group pretreated with α-monolinolein was 40% even at 11 weeks. In addition, when comparing the average number of tumors per mouse, the DMBA + TPA group was 4.8 at week 13.
, whereas DMBA 10-monolinolein + T
The PA group had 2.7 pieces.
以上の結果より、α−モノリノレインはTPAによる発
癌プロモーションを著明に阻害する抗発癌プロモーター
であることが示される。The above results indicate that α-monolinolein is an anti-carcinogenic promoter that significantly inhibits carcinogenic promotion by TPA.
本発明の抗発癌プロモーターであるα−モノリノレイン
は下記の方法により調整することができる。α-Monolinolein, which is an anti-carcinogenic promoter of the present invention, can be regulated by the following method.
天然資源から採取するには例えば犬豆池,ハトムギ油,
綿実油,米ヌガ油等の植物油から分離・禎製することが
できる。また、酸触媒や酵素を用いたグリセリンのエス
テル化,エステル交換や対応するトリグリセリド,ジグ
リセリドの部分加水分解等の公知の合成法を利用するこ
ともできる。For example, inumameike, pearl barley oil,
It can be separated and purified from vegetable oils such as cottonseed oil and rice nougat oil. Further, known synthetic methods such as esterification and transesterification of glycerin using an acid catalyst or an enzyme, and partial hydrolysis of corresponding triglycerides and diglycerides can also be used.
本発明の抗発癌プロモーターはα.モノリノレインまた
はそれを有効成分として含みその有効且つ非毒性量を含
有する組成物の形で用いることができ、例えば経口剤と
しては、錠剤,カプセル剤,トローチ剤,か粒剤,散剤
等の固体製剤あるいは水剤,シロップ剤等の液剤として
用いることが出来る。そして、これら各種の製剤は慣用
の無機又は有機の、或るいは固体又は液体の医薬製剤用
単体を用いて公知の方法で製造することができる。The anti-carcinogenic promoter of the present invention is α. It can be used in the form of monolinolein or a composition containing it as an active ingredient in an effective and non-toxic amount.For example, as an oral preparation, solid forms such as tablets, capsules, troches, granules, powders, etc. It can be used as a preparation or a solution such as a solution or syrup. These various preparations can be manufactured by known methods using conventional inorganic or organic, solid or liquid pharmaceutical preparations.
(実施例)
以下に、実施例に基づいて本発明をより詳細に説明する
。(Example) Below, the present invention will be described in more detail based on Examples.
実施例1
脱穀したハトムキ種子2kgをヘキサンに浸漬しろ過に
よって得られる浸出液を濃縮しヘキサンを留去すること
により87gのオイルを得た。Example 1 87 g of oil was obtained by immersing 2 kg of threshed pigeon berry seeds in hexane, filtering the resulting leachate, concentrating the hexane, and distilling off the hexane.
次にこれをヘキサンとメタノールで分配し39gのオイ
ルをヘキサン層から得、このものをヘキサン/酢酸エチ
ルを溶出液とするシリカゲル力ラムクロマトにより、ト
リグリセリド画分,ジグリセリド画分,遊離脂肪酸画分
,ステロール画分,モノグリセリド画分に分画した。Next, this was partitioned between hexane and methanol to obtain 39 g of oil from the hexane layer, which was subjected to silica gel column chromatography using hexane/ethyl acetate as the eluent to separate triglyceride fraction, diglyceride fraction, free fatty acid fraction, It was fractionated into a sterol fraction and a monoglyceride fraction.
モノグリセリド画分はさらにシリカゲル力ラムクロマト
により精製を行うことによってα−モノリノレインとα
.モノオレインに分離することができた。The monoglyceride fraction was further purified by silica gel column chromatography to separate α-monolinolein and α-monolinolein.
.. It was possible to separate it into monoolein.
このようにして単離したα.モノリノレインは各種スペ
クトルの測定において下記の物理定数を示し、これらの
値は標準のα−モノリノレインのそれと一致した。Thus isolated α. Monolinolein showed the following physical constants in various spectra measurements, and these values agreed with those of standard α-monolinolein.
IR(V) : 1744cm−1
LH−NMR(δppm) : 5.34(4H),
4.17(2H), 3.93(IH),3.70(L
H), 3.59(LH), 2.79(2H), 2
.35(4H), 2.04(4H),1.63(2H
), 1.31−1.25(IOH), 0.88(3
H) in CDC1313C−NMR(δppm)
: 174.3, 130.1, 129.7, 12
8.1,127.9, 70.3, 65.2, 63
.4, 34.2, 31.9, 29.8, 29.
7, 29.5,29.3, 29.3, 29.1,
27.2, 24.9, 22.7, 14.1 i
n CDCI3FD−MS(m/z) : 354(M
), 355(M + H)実施例2
7週齢の雌のICRマウス1群5匹3群を使用し、背部
皮膚に1匹当たりDMBA,390nmolを1回だけ
塗布した。1週間後から、TPA1.7nmolを週に
2回塗布することによりプロモーション活性を調べこれ
をコントロールとした。これに対し、TPAを塗布する
1時間前に501lgのα−モノリノレインを塗布し、
上記のTPA塗布のみのコントロールのプロモーション
活性と前述の方法により比較検討しな。IR (V): 1744 cm-1 LH-NMR (δppm): 5.34 (4H),
4.17 (2H), 3.93 (IH), 3.70 (L
H), 3.59 (LH), 2.79 (2H), 2
.. 35 (4H), 2.04 (4H), 1.63 (2H
), 1.31-1.25 (IOH), 0.88 (3
H) in CDC1313C-NMR (δppm)
: 174.3, 130.1, 129.7, 12
8.1, 127.9, 70.3, 65.2, 63
.. 4, 34.2, 31.9, 29.8, 29.
7, 29.5, 29.3, 29.3, 29.1,
27.2, 24.9, 22.7, 14.1 i
n CDCI3FD-MS (m/z): 354 (M
), 355 (M + H) Example 2 Three groups of 7-week-old female ICR mice (5 mice per group) were used, and 390 nmol of DMBA per mouse was applied only once to the back skin. After one week, 1.7 nmol of TPA was applied twice a week to examine the promotional activity and this was used as a control. On the other hand, 501 lg of α-monolinolein was applied 1 hour before applying TPA.
Compare the promotional activity of the TPA-only control with the method described above.
DMBA+TPA群は6週目から腫瘍が発生し、8週で
ハ100%の腫瘍発生頻度に達したが、これに対し、α
−モノリノレインを前処理したDMBA十〇−モノリノ
レイン+TPA群の腫瘍発生頻度は11週目で40%で
あった。Tumors occurred in the DMBA + TPA group from the 6th week and reached 100% tumor incidence in the 8th week;
-The frequency of tumor occurrence in the monolinolein-pretreated DMBA10-monolinolein+TPA group was 40% at the 11th week.
また、マウス1匹当たりの平均腫瘍個数は、13週目で
DMBAfTPA群が4.8個であるのに対し、DMB
A+a−モ/ ’) / レ{ > 十’r’pA/i
’P ハ2.71固であった。Furthermore, the average number of tumors per mouse was 4.8 in the DMBAfTPA group at week 13, whereas
A+a-mo/')/Re{>ten'r'pA/i
'P was 2.71 hard.
(発明の効果)
従って、本発明のα−モノリノレインを有効成分として
含む抗発癌プロモーターは発癌の予防を目的とする医薬
品,健康食品,機能性食品として用いることができる。(Effects of the Invention) Therefore, the anti-carcinogenic promoter of the present invention containing α-monolinolein as an active ingredient can be used as a pharmaceutical, health food, or functional food for the purpose of preventing carcinogenesis.
また、本発明の発癌プロモーション阻害剤の有効成分で
あるα−モノリノレインはEBウィルス・ゲノムの発現
を阻害することがら抗ウィルス剤及び制ガン剤としての
利用も考えられる。Furthermore, since α-monolinolein, which is an active ingredient of the cancer promotion inhibitor of the present invention, inhibits the expression of the EB virus genome, it can also be used as an antiviral agent and an anticancer agent.
Claims (1)
ターAnti-carcinogenic promoter containing α-monolinolein as an active ingredient
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1060535A JPH02240019A (en) | 1989-03-13 | 1989-03-13 | Anti-carcinogenic promoter |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1060535A JPH02240019A (en) | 1989-03-13 | 1989-03-13 | Anti-carcinogenic promoter |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH02240019A true JPH02240019A (en) | 1990-09-25 |
Family
ID=13145094
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP1060535A Pending JPH02240019A (en) | 1989-03-13 | 1989-03-13 | Anti-carcinogenic promoter |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPH02240019A (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06511479A (en) * | 1991-06-24 | 1994-12-22 | ウィメンズ アンド チルドレンズ ホスピタル | Methods and compositions for treating malaria and other diseases |
JP2005194222A (en) * | 2004-01-06 | 2005-07-21 | Otsuka Pharmaceut Factory Inc | Cytokine inducer |
JP2006502193A (en) * | 2002-09-28 | 2006-01-19 | 大鵬 李 | Yokuinin oil soft capsule for treating prostate disease |
-
1989
- 1989-03-13 JP JP1060535A patent/JPH02240019A/en active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH06511479A (en) * | 1991-06-24 | 1994-12-22 | ウィメンズ アンド チルドレンズ ホスピタル | Methods and compositions for treating malaria and other diseases |
JP2006502193A (en) * | 2002-09-28 | 2006-01-19 | 大鵬 李 | Yokuinin oil soft capsule for treating prostate disease |
JP4718836B2 (en) * | 2002-09-28 | 2011-07-06 | 大鵬 李 | Yokuinin oil soft capsule for treating prostate disease |
JP2005194222A (en) * | 2004-01-06 | 2005-07-21 | Otsuka Pharmaceut Factory Inc | Cytokine inducer |
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