{"id":6401,"date":"2024-08-06T11:54:58","date_gmt":"2024-08-06T11:54:58","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=6401"},"modified":"2024-08-06T11:54:58","modified_gmt":"2024-08-06T11:54:58","slug":"lotus-leaf-alkaloid-on-akt-mtor-4ebp1","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/hu\/lotuszlevel-alkaloid-az-akt-mtor-4ebp1-en\/","title":{"rendered":"A l\u00f3tuszlev\u00e9l alkaloid g\u00e1tl\u00f3 hat\u00e1s\u00e1nak vizsg\u00e1lata az Akt\/mTOR\/4EBP1 glikol\u00edzis \u00fatvonalra \u00e9s antiproliferat\u00edv hat\u00e1sa az epek\u0151carcinoma sejtekre"},"content":{"rendered":"

A l\u00f3tuszlev\u00e9l alkaloid g\u00e1tl\u00f3 hat\u00e1s\u00e1nak vizsg\u00e1lata az Akt\/mTOR\/4EBP1 glikol\u00edzis \u00fatvonalra \u00e9s antiproliferat\u00edv hat\u00e1sa az epek\u0151carcinoma sejtekre
\nA kolangi\u00f3karcin\u00f3m\u00e1t (CCA) anat\u00f3miai elhelyezked\u00e9s alapj\u00e1n extrahepatikus kolangi\u00f3karcin\u00f3m\u00e1ra (extrahepatikus kolangi\u00f3karcin\u00f3ma) \u00e9s intrahepatikus kolangi\u00f3karcin\u00f3m\u00e1ra (ICC) osztj\u00e1k. B\u00e1r az ICC az els\u0151dleges m\u00e1jr\u00e1knak csak 10% \u00e9s 20% k\u00f6z\u00f6tti r\u00e9sz\u00e9t teszi ki, a korai st\u00e1diumban igen alattomos, magas posztoperat\u00edv ki\u00fajul\u00e1si ar\u00e1nnyal \u00e9s rossz progn\u00f3zissal. Az ut\u00f3bbi \u00e9vtizedekben az ICC el\u0151fordul\u00e1si ar\u00e1nya \u00e9s mortalit\u00e1sa \u00c1zsi\u00e1ban, s\u0151t a vil\u00e1gon is folyamatosan emelkedett. Az el\u0151rehaladott ICC els\u0151 vonalbeli kemoter\u00e1pi\u00e1s programja hajlamos a gy\u00f3gyszerrezisztenci\u00e1ra \u00e9s a mell\u00e9khat\u00e1sokra a hossz\u00fa t\u00e1v\u00fa haszn\u00e1lat ut\u00e1n, ez\u00e9rt biztons\u00e1gos \u00e9s hat\u00e9kony ter\u00e1pi\u00e1s gy\u00f3gyszerek felt\u00e1r\u00e1s\u00e1ra van sz\u00fcks\u00e9g.
\nA n\u00f6v\u00e9nyekb\u0151l \u00e9s \u00e1llatokb\u00f3l sz\u00e1rmaz\u00f3, daganatellenes hat\u00e1s\u00fa term\u00e9szetes gy\u00f3gy\u00e1szati hat\u00f3anyagok sz\u0171r\u00e9se mindig is a hazai \u00e9s nemzetk\u00f6zi kutat\u00e1sok egyik legjelent\u0151sebb ter\u00fclete volt. A nuciferin (NUF) a Nymphaeaceae csal\u00e1dba tartoz\u00f3 Nelumbo nucifera Gaertn sz\u00e1r\u00edtott leveleib\u0151l sz\u00e1rmazik. Bizonyos tumorsejt-ellenes aktivit\u00e1ssal rendelkezik, de ICC-sejtekre gyakorolt hat\u00e1s\u00e1r\u00f3l ritk\u00e1n sz\u00e1moltak be. Ez a tanulm\u00e1ny a l\u00f3tuszlev\u00e9l alkaloid hat\u00e1s\u00e1t vizsg\u00e1lta a HuCCT1 sejtek prolifer\u00e1ci\u00f3j\u00e1ra \u00e9s glikol\u00edzis folyamat\u00e1ra, \u00e9s el\u0151zetesen felt\u00e1rta a hat\u00e1smechanizmus\u00e1t, elm\u00e9leti alapot ny\u00fajtva a biztons\u00e1gos \u00e9s hat\u00e9kony ICC ter\u00e1pi\u00e1s gy\u00f3gyszerek kifejleszt\u00e9s\u00e9hez.<\/p>\n

\"\"\"\"\"\"\"\"\"\"\"\"\"\"\"\"\"\"<\/p>\n

A modern farmakol\u00f3giai kutat\u00e1sok azt mutatj\u00e1k, hogy a l\u00f3tuszlev\u00e9lb\u0151l kivont l\u00f3tuszlev\u00e9l alkaloid akt\u00edv \u00f6sszetev\u0151je bizonyos n\u00f6veked\u00e9st g\u00e1tl\u00f3 hat\u00e1ssal van sz\u00e1mos daganatos sejtre, p\u00e9ld\u00e1ul m\u00e1jr\u00e1kra, t\u00fcd\u0151r\u00e1kra, mellr\u00e1kra, \u00e9s jav\u00edthatja a kemoter\u00e1pi\u00e1s gy\u00f3gyszerekkel szembeni \u00e9rz\u00e9kenys\u00e9g\u00e9t. Ez a vizsg\u00e1lat meg\u00e1llap\u00edtotta, hogy a l\u00f3tuszlev\u00e9l alkaloid bizonyos koncentr\u00e1ci\u00f3ja jelent\u0151sen g\u00e1tolja a HuCCT1 sejtek prolifer\u00e1ci\u00f3j\u00e1t in vitro, \u00e9s pozit\u00edvan korrel\u00e1l a gl\u00fck\u00f3zfogyaszt\u00e1s \u00e9s a lakt\u00e1ttermel\u00e9s cs\u00f6kkent\u00e9s\u00e9vel. A sz\u00e9nhidr\u00e1tok fontos energiaforr\u00e1sok a sejtek \u00e9lettev\u00e9kenys\u00e9g\u00e9ben, \u00e9s a Warburg-hat\u00e1s azt jelzi, hogy a r\u00e1kos sejtek m\u00e9g norm\u00e1l oxig\u00e9nell\u00e1t\u00e1s mellett is ink\u00e1bb a glikol\u00edzisen kereszt\u00fcl szolg\u00e1ltatnak energi\u00e1t, mint az aerob anyagcsere-utakon kereszt\u00fcl. A glikol\u00edzis magas szintje gyors energi\u00e1t biztos\u00edthat a r\u00e1kos sejtek n\u00f6veked\u00e9s\u00e9hez, \u00e9s term\u00e9kei, p\u00e9ld\u00e1ul a piruvinsav \u00e9s a tejsav szint\u00e9n nyersanyagot szolg\u00e1ltatnak a r\u00e1kos sejtek anyagainak szint\u00e9zis\u00e9hez, \u00e9s el\u0151seg\u00edtik a r\u00e1kos sejtek \u00e1tt\u00e9tk\u00e9pz\u00e9s\u00e9t \u00e9s inv\u00e1zi\u00f3j\u00e1t. Ez\u00e9rt felt\u00e9telezhet\u0151, hogy a HuCCT1 sejtek prolifer\u00e1ci\u00f3j\u00e1nak l\u00f3tuszlev\u00e9l alkaloid\u00e1k \u00e1ltali g\u00e1tl\u00e1sa a sejtek glikol\u00edzis anyagcser\u00e9j\u00e9nek g\u00e1tl\u00e1s\u00e1val f\u00fcgg \u00f6ssze.
\nA h\u00e1l\u00f3zati farmakol\u00f3giai elemz\u00e9s magas korrel\u00e1ci\u00f3t tal\u00e1lt a matrin \u00e9s a HIF-1 \u03b1, valamint az olyan c\u00e9lpontok k\u00f6z\u00f6tt, mint a TNF, INS, EGFR stb. A HIF-1 \u03b1 sz\u00e1mos folyamatban r\u00e9szt vesz, p\u00e9ld\u00e1ul a gl\u00fck\u00f3z anyagcser\u00e9ben, a sejtprolifer\u00e1ci\u00f3ban, az inv\u00e1zi\u00f3ban \u00e9s metaszt\u00e1zisban, valamint a tumorsejtek gyullad\u00e1sos v\u00e1lasz\u00e1ban. Aktiv\u00e1lhatja a gl\u00fck\u00f3ztranszporter (GLUT) \u00e9s k\u00fcl\u00f6nb\u00f6z\u0151 glikolitikus enzimek, mint a HK2, PKM2 \u00e9s a piruv\u00e1t-dehidrogen\u00e1z kin\u00e1z 1 (PDK1) aktivit\u00e1s\u00e1t, \u00e9s k\u00f6zvetlen\u00fcl r\u00e9szt vesz a glikol\u00edzis folyamat\u00e1ban, nagyban el\u0151seg\u00edtve a tumor progresszi\u00f3j\u00e1t. A hexokin\u00e1z (HK) \u00e9s a piruv\u00e1t-kin\u00e1z (PK) k\u00e9t kulcsfontoss\u00e1g\u00fa kin\u00e1z a glikol\u00edzis folyamat\u00e1ban, amelyek a folyamat kezdeti \u00e9s v\u00e9gs\u0151 szakasz\u00e1t szab\u00e1lyozz\u00e1k. Ez a tanulm\u00e1ny azt tal\u00e1lta, hogy a HIF-1 \u03b1 \u00e9s a kulcsfontoss\u00e1g\u00fa glikolitikus enzimek, a HK2 \u00e9s a PKM2 mRNS-szintje \u00e9s feh\u00e9rjeexpresszi\u00f3ja a sejtekben fokozatosan cs\u00f6kkent a l\u00f3tuszlev\u00e9l alkaloid koncentr\u00e1ci\u00f3j\u00e1nak n\u00f6veked\u00e9s\u00e9vel. Ez\u00e9rt felt\u00e9telezhet\u0151, hogy a l\u00f3tuszlev\u00e9l alkaloid a HIF-1 \u03b1 aktivit\u00e1s\u00e1nak cs\u00f6kkent\u00e9s\u00e9vel befoly\u00e1solhatja a HuCCT1 sejtek glikol\u00edzisfolyamat\u00e1t.
\nA HIF-1 egy olyan transzkripci\u00f3s faktor, amelyre a sejtek alacsony oxig\u00e9nszint\u0171 vagy hipoxi\u00e1s k\u00f6rnyezetben reag\u00e1lnak, \u00e9s amely k\u00e9t alegys\u00e9gb\u0151l \u00e1ll: A HIF-1 \u03b1 prolin-maradv\u00e1nya normoxikus k\u00f6r\u00fclm\u00e9nyek k\u00f6z\u00f6tt hajlamos a hidroxil\u00e1l\u00f3d\u00e1sra, \u00e9s k\u00f6t\u0151dik a hangol\u00f3 molekul\u00e1j\u00e1hoz (von Hippel Lindau, pVHL), amely ubikvitin\u00e1ci\u00f3val lebomlik. Alacsony oxig\u00e9nszint\u0171 k\u00f6rnyezetben a proil-hidroxil\u00e1z dom\u00e9nt tartalmaz\u00f3 feh\u00e9rj\u00e9k (PHD) aktivit\u00e1sa cs\u00f6kken, ami a HIF-1 \u03b1 jelent\u0151s felhalmoz\u00f3d\u00e1s\u00e1hoz vezet, amely ezut\u00e1n a sejtmagba v\u00e1ndorol, hogy dimert k\u00e9pezzen a HIF-1 \u03b2-vel. A dimer ezut\u00e1n a hipoxi\u00e1s v\u00e1laszelemhez (HRE) k\u00f6t\u0151dik, hogy el\u0151seg\u00edtse a HIF-1 c\u00e9lg\u00e9nek transzkripci\u00f3j\u00e1t. Ezenk\u00edv\u00fcl a HIF-1 \u03b1 oxig\u00e9nt\u0151l f\u00fcggetlen m\u00f3don is aktiv\u00e1l\u00f3dhat, p\u00e9ld\u00e1ul a PI3K\/Akt\/mTOR jel\u00e1tviteli kaszk\u00e1d felszab\u00e1lyozhatja a HIF-1 \u03b1 transzkripci\u00f3j\u00e1t \u00e9s transzl\u00e1ci\u00f3j\u00e1t az eukari\u00f3ta transzl\u00e1ci\u00f3 inici\u00e1ci\u00f3s faktor 4E (eIF4E) k\u00f6t\u0151 feh\u00e9rje 1 (4EBP1) integrit\u00e1s\u00e1nak megbont\u00e1s\u00e1val. Egyes tud\u00f3sok ennek az oxig\u00e9nt\u0151l f\u00fcggetlen HIF-1 \u03b1 jelnek az aktiv\u00e1l\u00e1si mechanizmus\u00e1t \"pszeudo-hipoxi\u00e1nak\" nevezik. Ebben a tanulm\u00e1nyban a KEGG-elemz\u00e9s kimutatta, hogy a matrin az ICC potenci\u00e1lis \u00fatvonalaira hat, a PI3K\/Akt jel\u00e1tviteli \u00fatvonal jelent\u0151s n\u00f6veked\u00e9s\u00e9vel. Az immunoblotting kimutatta, hogy a matrin k\u00e9pes cs\u00f6kkenteni az mTOR \u00e9s a 4EBP1 feh\u00e9rj\u00e9k foszforil\u00e1ci\u00f3s szintj\u00e9t a HuCCT1 sejtekben, \u00e9s a teljes p-AktTrr308 feh\u00e9rje cs\u00f6kken\u0151 tendenci\u00e1t mutatott, ami arra utal, hogy a HIF-1 \u03b1 transzkripci\u00f3 \u00e9s transzl\u00e1ci\u00f3 szintj\u00e9nek matrin \u00e1ltali lefel\u00e9 szab\u00e1lyoz\u00e1sa az Akt\/mTOR\/4EBP1 jel\u00e1tviteli \u00fatvonal g\u00e1tl\u00e1s\u00e1val f\u00fcgghet \u00f6ssze.<\/p>\n

T\u00f6bb tanulm\u00e1ny kimutatta, hogy a l\u00f3tuszlev\u00e9l alkaloidok a tumorsejtek in vitro apopt\u00f3zis\u00e1nak kiv\u00e1lt\u00e1sa, az inv\u00e1zi\u00f3 \u00e9s az \u00e1tt\u00e9tk\u00e9pz\u0151d\u00e9s g\u00e1tl\u00e1sa, valamint a k\u00fcl\u00f6nb\u00f6z\u0151 ciklusok blokkol\u00e1sa mellett a l\u00f3tuszlev\u00e9l alkaloidok k\u00e9sleltethetik az ektopikusan \u00e1t\u00fcltetett tumorok n\u00f6veked\u00e9s\u00e9t meztelen egerekben, \u00e9s jelent\u0151s tumorellenes hat\u00e1st fejtenek ki. A f\u0151 mechanizmus a sejtciklussal \u00e9s az apopt\u00f3zissal kapcsolatos feh\u00e9rjeexpresszi\u00f3nak a l\u00f3tuszlev\u00e9l alkaloid\u00e1k \u00e1ltali szab\u00e1lyoz\u00e1s\u00e1val, a specifikus g\u00e9nek k\u00f6zvetlen c\u00e9lz\u00e1s\u00e1val, a jel\u00e1tviteli \u00fatvonalak, mint p\u00e9ld\u00e1ul a PI3K Akt, Wnt\/\u03b2 - katenin, SOX2 Akt, STAT3 \u00e9s TLR4\/NF - \u03ba B g\u00e1tl\u00e1s\u00e1val f\u00fcgg \u00f6ssze. Ez a tanulm\u00e1ny el\u0151zetesen meg\u00e1llap\u00edtotta, hogy a l\u00f3tuszlev\u00e9l alkaloid\u00e1k g\u00e1tolj\u00e1k az intrahepatikus kolangi\u00f3karcin\u00f3ma sejtek prolifer\u00e1ci\u00f3j\u00e1t, val\u00f3sz\u00edn\u0171leg az Akt\/mTOR\/4EBP1 jel\u00e1tviteli \u00fatvonal \u00e1ltal szab\u00e1lyozott sejtglikol\u00edzis folyamat elnyom\u00e1sa r\u00e9v\u00e9n. A kett\u0151 k\u00f6z\u00f6tti bels\u0151 logikai kapcsolatot a kutat\u00e1s k\u00f6vetkez\u0151 l\u00e9p\u00e9s\u00e9ben felt\u00e1rjuk, hogy tiszt\u00e1zzuk a l\u00f3tuszlev\u00e9l alkaloid\u00e1k ICC-ellenes mechanizmus\u00e1t, \u00e9s elm\u00e9leti alapot biztos\u00edtsunk a l\u00f3tuszlev\u00e9lforr\u00e1sok \u00e9s a klinikai alkalmaz\u00e1sok m\u00e9lyrehat\u00f3 fejleszt\u00e9s\u00e9hez.<\/p>","protected":false},"excerpt":{"rendered":"

Study on the inhibitory effect of lotus leaf alkaloid on Akt\/mTOR\/4EBP1 glycolysis pathway and its anti proliferative effect on cholangiocarcinoma cells Cholangiocarcinoma (CCA) is divided into extrahepatic cholangiocarcinoma (extrahepatic cholangiocarcinoma) and intrahepatic cholangiocarcinoma (ICC) based on anatomical location. Although ICC accounts for only 10% to 20% of primary liver cancer, it is highly insidious in […]<\/p>","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"yoast_head":"\nStudy on the inhibitory effect of lotus leaf alkaloid on Akt\/mTOR\/4EBP1 glycolysis pathway and its anti proliferative effect on cholangiocarcinoma cells - China Chemical Manufacturer<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/longchangextracts.com\/hu\/lotuszlevel-alkaloid-az-akt-mtor-4ebp1-en\/\" \/>\n<meta property=\"og:locale\" content=\"hu_HU\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Study on the inhibitory effect of lotus leaf alkaloid on Akt\/mTOR\/4EBP1 glycolysis pathway and its anti proliferative effect on cholangiocarcinoma cells - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"Study on the inhibitory effect of lotus leaf alkaloid on Akt\/mTOR\/4EBP1 glycolysis pathway and its anti proliferative effect on cholangiocarcinoma cells Cholangiocarcinoma (CCA) is divided into extrahepatic cholangiocarcinoma (extrahepatic cholangiocarcinoma) and intrahepatic cholangiocarcinoma (ICC) based on anatomical location. 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