JP2019505522A - ポリフェノール化合物を有効成分として含む癌治療用薬学組成物 - Google Patents
ポリフェノール化合物を有効成分として含む癌治療用薬学組成物 Download PDFInfo
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Abstract
【選択図】 図12
Description
第1段階(G1):高分化性癌−分化性が良い段階(well differentiated)
第2段階(G2):中分化性癌−分化性が中間の段階(Moderately differentiated)
第3段階(G3):低分化性癌−分化性が悪い段階(Poorly differentiated)
第4段階(G4):未分化性癌−未分化段階(Undifferentiated)
低分化性癌は、高分化性または中分化性癌に比べて癌幹細胞を多量含み、腫瘍の境界が不明であり、転移が速く、治療効果がわずかであり、治療後にも予後が良くないことが知られている。
実施例1−1.胃癌細胞に対するゴシポールの増殖抑制効果の確認
胃癌細胞株に対するゴシポールの増殖抑制効果を確認するために、6種類の互いに異なる胃癌細胞株(MKN28、MKN45、AGS、SNU668、Kato3およびHS746T)を用意した。韓国細胞株銀行(Korean Cell Line Bank)または国際細胞株銀行(ATCC)において公知の細胞株の定義は表1に記載した。
ATP(アデノシン三リン酸、adenosine triphosphate)は生物のエネルギー源で、細胞内ATP合成が抑制されると、エネルギー代謝の活性度が減少する。実施例1−1の胃癌細胞株MKN28、MKN45およびSNU668について、ゴシポールのATP合成抑制効果を確認した。
実施例1−1〜1−2からゴシポールが癌細胞に対して細胞死を促進する効果があると期待され、下記の実験を進行させた。
実施例1−1の互いに異なる6種類の胃癌細胞株(MKN28、MKN45、AGS、SNU668、Kato3およびHS746T)をそれぞれ1×103〜1×104/wellずつ100mmの培養皿で24時間培養し、ゴシポールを0または10μMの濃度で処理した後、追加的に24時間培養した。ゴシポール処理された細胞を得て70%エタノールで固定し、冷たい1XPBSで洗浄後、暗室でPI+RNase溶液(DPBS、pH7.4)で30分間染色した。前記細胞を流細胞分析(FACS)して、DNA含有量で細胞週期別の比率を分析した。その結果を図5に示した。
実施例2−1.胃癌幹細胞に対するゴシポールの増殖抑制効果の確認
前記実施例1からゴシポールが低分化性癌の成長抑制に有意な効果があることが分かり、低分化性癌が癌幹細胞を多く含む点を考慮するとき、ゴシポールが癌幹細胞の成長抑制にも有意な効果があると期待され、下記の実験を進行させた。
一般の胃癌細胞であるAGS(以下、PAGS、parental AGS)から4週間の持続的な代謝ストレス下で生存した癌細胞を、癌幹細胞マーカーの発現、腫瘍球(tumor spheroid)形成能、標準抗癌剤の耐性、免疫抑制マウスから腫瘍形成能などの表現型分析方法により選択分離されたAGS細胞(以下、SAGS、selected AGS、Cell Death Dis.2015Jul2;6:e1805)について、ゴシポールによる成長抑制効果を確認した。細胞培養および生存率の測定方法は、前記実施例2−1と同様に進行させた。実験結果、PAGSのIC50ゴシポール濃度は4.2mMであるのに対し、癌幹細胞の性格を有するSAGSのIC50ゴシポール濃度は2.8mMであることが明らかになり、同じ起源の細胞でも幹細胞の性格を有するか否かによってゴシポールに対する薬物敏感性が著しく異なることが分かった。前記結果を図8に記載した。
実施例3−1.ゴシポールおよび既存の薬剤を併用処理した胃癌細胞の細胞成長の分析
AGS、SNU484、SNU668、MKN28、Hs746T、MKN45、およびSNU719胃癌幹細胞をそれぞれ5×103〜4×104/wellずつ96−ウェルプレートに接種し、24時間培養した。この後、各ウェルにゴシポール、フェンホルミン(Phenformin)、およびイリノテカン(Irinotecan)薬物を表3の通りに投与し、追加的に24時間培養した。この後、細胞を4℃の条件で1時間50体積%TCA(trichloroacetic acid、最終濃度10%TCA)で固定し、蒸留水洗浄後、室温で水分乾燥した。固定された細胞の入っているそれぞれのウェルを1体積%酢酸溶液に溶解した0.4重量%スルホローダミンB(Sulforhodamine B)100μlで10分間染色処理し、1体積%酢酸溶液で4回洗浄した。染色されたプレートは室温乾燥した後、各ウェルごとに100μlの10mMトリス緩衝液(Tris buffer、pH7.5)を添加し、溶出した色素を515nmの波長で吸光度測定した。前記結果から導出された胃癌細胞株の成長抑制効果を図9に記載した。
前記実施例3−1の対照群および実験例1〜7の細胞について、ミトコンドリア細胞膜の活性度分析を実施した。ミトコンドリア細胞膜の活性は、細胞内エネルギー生産の指標として利用される。まず、各細胞試料の薬物投与処理が終わる20分前に、100nM TMRE(tetramethylrodamine ester、ab113852、Abcam)を培養培地に添加し、細胞を冷PBSで3回洗浄した後、流細胞分析器で585nm(FL−2)チャネルを用いて細胞の蛍光強度を測定した。前記結果を図10に記載した。
前記実施例3−1の対照群および実験例1〜7の細胞について、それぞれの薬物を投与し、12時間、24時間、48時間、および72時間経過時点の試料を獲得して細胞死分析を実施した。まず、細胞を冷PBSで洗浄し、1400rpmで3分間遠心分離した後、1×106細胞/mlの濃度で再懸濁した。前記細胞懸濁液100μlを5mlの培養チューブに移し、アネキシンV−FITCおよびPI染色液をそれぞれ5μl添加し、暗い室温で15分間反応させた後、1X結合緩衝液400μlを添加して、FACS流細胞分析器(BD Falcon、Bedford、MA、USA)で分析した。前記FACSの結果および数値で換算したグラフを図11および図12に記載した。実験結果、すべての時間帯でゴシポール、フェンホルミン、およびイリノテカンを併用投与した場合に、ゴシポール、フェンホルミン、またはイリノテカンをそれぞれ単独投与した場合とゴシポールおよびフェンホルミンを併用投与した場合より有意に癌細胞死滅が増加することが明らかになった。
Claims (19)
- ポリフェノール化合物を有効成分として含む癌予防または治療用薬学組成物。
- 前記ポリフェノール化合物は、サフロール(safrole)、ゴシポール(Gossypol)、およびクマリン(coumarins)から構成されるグループより選択されるいずれか1つ以上である、請求項1に記載の薬学組成物。
- 前記ポリフェノール化合物は、0.5〜500mMの量で含まれる、請求項1に記載の薬学組成物。
- 前記薬学組成物は、ビグアニド系化合物を追加的に含む、請求項1に記載の薬学組成物。
- 前記ビグアニド系化合物は、メトホルミン(metformin)、ブホルミン(buformin)、およびフェンホルミン(phenformin)から構成されるグループより選択されるいずれか1つ以上である、請求項4に記載の薬学組成物。
- 前記薬学組成物は、抗癌剤を追加的に含む、請求項4に記載の薬学組成物。
- 前記抗癌剤は、イリノテカン(Irinotecan)である、請求項6に記載の薬学組成物。
- 前記癌は、癌幹細胞を含むものである、請求項1に記載の薬学組成物。
- 前記癌は、胃癌である、請求項1に記載の薬学組成物。
- 前記治療は、癌幹細胞を含む癌細胞の数的増加を抑制させたり、量的増殖を抑制させたり、細胞を死滅させたり、癌幹細胞を含む癌組織の大きさを減少または維持させたり、または癌幹細胞を含む癌組織内の新生血管の発達を抑制することを含む、請求項1に記載の薬学組成物。
- ポリフェノール化合物を有効成分として含む癌転移抑制用薬学組成物。
- 前記ポリフェノール化合物は、サフロール(safrole)、ゴシポール(Gossypol)、およびクマリン(coumarins)から構成されるグループより選択されるいずれか1つ以上である、請求項11に記載の薬学組成物。
- 前記ポリフェノール化合物は、0.5〜500mMの量で含まれる、請求項11に記載の薬学組成物。
- 前記薬学組成物は、ビグアニド系化合物を追加的に含む、請求項11に記載の薬学組成物。
- 前記ビグアニド系化合物は、メトホルミン(metformin)、ブホルミン(buformin)、およびフェンホルミン(phenformin)から構成されるグループより選択されるいずれか1つ以上である、請求項14に記載の薬学組成物。
- 前記薬学組成物は、抗癌剤を追加的に含む、請求項14に記載の薬学組成物。
- 前記抗癌剤は、イリノテカン(Irinotecan)である、請求項16に記載の薬学組成物。
- 前記癌は、癌幹細胞を含むものである、請求項11に記載の薬学組成物。
- 前記癌は、胃癌である、請求項11に記載の薬学組成物。
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KR102428313B1 (ko) * | 2018-07-09 | 2022-08-03 | 연세대학교 산학협력단 | 알데히드 억제제, 및 항암제를 포함하는 뇌암 치료용 약학조성물 |
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WO2020213939A1 (ko) * | 2019-04-15 | 2020-10-22 | 주식회사 진센 | 항암제의 병용투여용 약학조성물 |
KR102349477B1 (ko) * | 2019-08-30 | 2022-01-10 | (주)프론트바이오 | 바이구아나이드 계열 화합물 및 플라본, 하이드록시플라본, 플라바논, 플라본 유도체, 하이드록시플라본 유도체, 플라바논 유도체의 복합제를 유효성분으로 함유하는 암 예방 또는 치료용 약학적 조성물 |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6114397A (en) * | 1990-07-12 | 2000-09-05 | The United States Of America As Represented By The Department Of Health And Human Services | Gossypol for the treatment of cancer |
JP2010529023A (ja) * | 2007-05-31 | 2010-08-26 | アセンタ セラピューティックス インコーポレイティッド | 疾患の処置のためのゴシポールの律動的投薬法 |
WO2015130109A1 (ko) * | 2014-02-27 | 2015-09-03 | 국립암센터 | 고시폴 및 펜포르민을 유효성분으로 함유하는 암 치료용 약제학적 조성물 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7432304B2 (en) * | 2001-05-30 | 2008-10-07 | The Regents Of The University Of Michigan | Small molecule antagonists of Bcl-2 family proteins |
AU2002305769B2 (en) | 2001-05-30 | 2007-07-19 | Georgetown University | Small molecule antagonists of Bcl2 family proteins |
BRPI0509182A (pt) | 2004-03-25 | 2007-09-18 | Univ Michigan | co-cristais de gossipol e uso dos mesmos |
US20090175869A1 (en) | 2007-05-31 | 2009-07-09 | Ascenta Therapeutics, Inc. | Pulsatile Dosing of Gossypol for Treatment of Disease |
WO2010114805A1 (en) | 2009-03-31 | 2010-10-07 | The Trustees Of The University Of Pennsylvania | Methods of treating cancer with phenformin |
KR101289033B1 (ko) | 2011-07-04 | 2013-07-23 | 한양대학교 산학협력단 | 암 줄기세포 성장 억제용 조성물 |
KR101765575B1 (ko) | 2015-02-02 | 2017-08-07 | 연세대학교 산학협력단 | 알데히드 억제제 및 비구아나이드 계열 화합물을 포함하는 암 줄기세포의 성장 억제용 약학적 조성물 |
WO2016126073A2 (ko) | 2015-02-02 | 2016-08-11 | 연세대학교 산학협력단 | 알데히드 억제제 및 비구아나이드 계열 화합물을 포함하는 암 줄기세포의 성장 억제용 약학적 조성물 |
KR101904893B1 (ko) | 2016-02-18 | 2018-10-10 | 연세대학교 산학협력단 | 폴리페놀 화합물을 유효성분으로 포함하는 암 치료용 약학조성물 |
-
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6114397A (en) * | 1990-07-12 | 2000-09-05 | The United States Of America As Represented By The Department Of Health And Human Services | Gossypol for the treatment of cancer |
JP2010529023A (ja) * | 2007-05-31 | 2010-08-26 | アセンタ セラピューティックス インコーポレイティッド | 疾患の処置のためのゴシポールの律動的投薬法 |
WO2015130109A1 (ko) * | 2014-02-27 | 2015-09-03 | 국립암센터 | 고시폴 및 펜포르민을 유효성분으로 함유하는 암 치료용 약제학적 조성물 |
JP2017506655A (ja) * | 2014-02-27 | 2017-03-09 | ナショナル キャンサー センター | 有効成分としてゴシポール及びフェンホルミンを含有するがん治療のための医薬組成物 |
Non-Patent Citations (4)
Title |
---|
CANCER BIOL. THER., 2015, VOL.16, NO.1, PP.77-87, JPN6019036680, ISSN: 0004272997 * |
ONCOTARGET, 2011, VOL.2, NO.12, PP.896-917, JPN6018016276, ISSN: 0004272999 * |
PROC. NATL. SCI. USA, 2014, VOL.111, NO.29, PP.10574-10579, JPN6019036684, ISSN: 0004272996 * |
SCIENCE, 2011, VOL.331, NO.6016, PP.456-461, JPN6019036681, ISSN: 0004272998 * |
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