{"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\/tr\/lotus-leaf-alkaloid-on-akt-mtor-4ebp1\/","title":{"rendered":"Lotus yapra\u011f\u0131 alkaloidinin Akt\/mTOR\/4EBP1 glikoliz yola\u011f\u0131 \u00fczerindeki inhibit\u00f6r etkisi ve kolanjiyokarsinom h\u00fccreleri \u00fczerindeki anti proliferatif etkisi \u00fczerine \u00e7al\u0131\u015fma"},"content":{"rendered":"

Lotus yapra\u011f\u0131 alkaloidinin Akt\/mTOR\/4EBP1 glikoliz yola\u011f\u0131 \u00fczerindeki inhibit\u00f6r etkisi ve kolanjiyokarsinom h\u00fccreleri \u00fczerindeki anti proliferatif etkisi \u00fczerine \u00e7al\u0131\u015fma
\nKolanjiyokarsinom (KKA), anatomik yerle\u015fimine g\u00f6re ekstrahepatik kolanjiyokarsinom (ekstrahepatik kolanjiyokarsinom) ve intrahepatik kolanjiyokarsinom (ICC) olarak ikiye ayr\u0131l\u0131r. ICC, primer karaci\u011fer kanserinin yaln\u0131zca 10% ila 20%'sini olu\u015fturmas\u0131na ra\u011fmen, erken evrelerde olduk\u00e7a sinsidir, y\u00fcksek postoperatif n\u00fcks oran\u0131 ve k\u00f6t\u00fc prognozu vard\u0131r. Son y\u0131llarda, Asya'da ve hatta d\u00fcnyada ICC insidans oran\u0131 ve mortalitesi giderek artmaktad\u0131r. \u0130lerlemi\u015f ICC i\u00e7in birinci basamak kemoterapi program\u0131, uzun s\u00fcreli kullan\u0131mdan sonra ila\u00e7 direncine ve advers ila\u00e7 reaksiyonlar\u0131na e\u011filimlidir, bu nedenle g\u00fcvenli ve etkili terap\u00f6tik ila\u00e7lar\u0131n ke\u015ffedilmesi gerekir.
\nBitkilerden ve hayvanlardan anti-t\u00fcm\u00f6r etkileri olan do\u011fal t\u0131bbi aktif bile\u015fenlerin taranmas\u0131, hem yurt i\u00e7inde hem de yurt d\u0131\u015f\u0131nda her zaman \u00f6nemli bir ara\u015ft\u0131rma konusu olmu\u015ftur. Nuciferine (NUF), Nymphaeaceae familyas\u0131ndan bir bitki olan Nelumbo nucifera Gaertn'in kurutulmu\u015f yapraklar\u0131ndan elde edilir. Belirli anti-t\u00fcm\u00f6r h\u00fccre aktivitesine sahiptir, ancak ICC h\u00fccreleri \u00fczerindeki etkisi nadiren rapor edilmi\u015ftir. Bu \u00e7al\u0131\u015fmada lotus yapra\u011f\u0131 alkaloidinin HuCCT1 h\u00fccrelerinin proliferasyonu ve glikoliz s\u00fcreci \u00fczerindeki etkileri ara\u015ft\u0131r\u0131lm\u0131\u015f ve g\u00fcvenli ve etkili ICC terap\u00f6tik ila\u00e7lar\u0131n\u0131n geli\u015ftirilmesi i\u00e7in teorik bir temel sa\u011flayarak etki mekanizmas\u0131 \u00f6nceden ara\u015ft\u0131r\u0131lm\u0131\u015ft\u0131r.<\/p>\n

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Modern farmakoloji ara\u015ft\u0131rmalar\u0131, lotus yapra\u011f\u0131ndan elde edilen lotus yapra\u011f\u0131 alkaloidinin aktif bile\u015feninin karaci\u011fer kanseri, akci\u011fer kanseri, meme kanseri gibi bir\u00e7ok t\u00fcm\u00f6r h\u00fccresi \u00fczerinde belirli bir anti b\u00fcy\u00fcme etkisine sahip oldu\u011funu ve kemoterapi ila\u00e7lar\u0131na duyarl\u0131l\u0131\u011f\u0131n\u0131 art\u0131rabilece\u011fini g\u00f6stermektedir. Bu \u00e7al\u0131\u015fma, belirli bir lotus yapra\u011f\u0131 alkaloid konsantrasyonunun HuCCT1 h\u00fccrelerinin in vitro \u00e7o\u011falmas\u0131n\u0131 \u00f6nemli \u00f6l\u00e7\u00fcde inhibe edebildi\u011fini ve glikoz t\u00fcketimini ve laktat \u00fcretimini azaltma ile pozitif ili\u015fkili oldu\u011funu bulmu\u015ftur. Karbonhidratlar h\u00fccresel ya\u015fam faaliyetlerinde \u00f6nemli enerji kaynaklar\u0131d\u0131r ve Warburg etkisi, normal oksijen ko\u015fullar\u0131nda bile kanser h\u00fccrelerinin aerobik metabolik yollardan ziyade glikoliz yoluyla tercihen enerji sa\u011flad\u0131\u011f\u0131n\u0131 g\u00f6sterir. Y\u00fcksek glikoliz seviyeleri kanser h\u00fccrelerinin b\u00fcy\u00fcmesi i\u00e7in h\u0131zl\u0131 enerji sa\u011flayabilir ve pir\u00fcvik asit ve laktik asit gibi \u00fcr\u00fcnleri de kanser h\u00fccresi maddelerinin sentezi i\u00e7in hammadde sa\u011flar ve kanser h\u00fccresi metastaz\u0131 ve istilas\u0131n\u0131 te\u015fvik eder. Bu nedenle, HuCCT1 h\u00fccre proliferasyonunun lotus yapra\u011f\u0131 alkaloidleri taraf\u0131ndan inhibe edilmesinin, h\u00fccresel glikoliz metabolizmas\u0131n\u0131n inhibisyonu ile ili\u015fkili oldu\u011fu tahmin edilmektedir.
\nA\u011f farmakoloji analizi, matrine ve HIF-1 \u03b1'n\u0131n yan\u0131 s\u0131ra TNF, INS, EGFR gibi hedefler aras\u0131nda y\u00fcksek bir korelasyon buldu. HIF-1 \u03b1, t\u00fcm\u00f6r h\u00fccrelerinde glikoz metabolizmas\u0131, h\u00fccre proliferasyonu, invazyon ve metastaz ve enflamatuar yan\u0131t gibi bir\u00e7ok s\u00fcre\u00e7te yer al\u0131r. Glikoz ta\u015f\u0131y\u0131c\u0131 (GLUT) ve HK2, PKM2 ve piruvat dehidrojenaz kinaz 1 (PDK1) gibi \u00e7e\u015fitli glikolitik enzimlerin aktivitesini aktive edebilir ve glikoliz s\u00fcrecine do\u011frudan kat\u0131larak t\u00fcm\u00f6r ilerlemesini b\u00fcy\u00fck \u00f6l\u00e7\u00fcde te\u015fvik edebilir. Heksokinaz (HK) ve piruvat kinaz (PK), glikoliz s\u00fcrecinde s\u0131ras\u0131yla s\u00fcrecin ilk ve son a\u015famalar\u0131n\u0131 d\u00fczenleyen iki anahtar kinazd\u0131r. Bu \u00e7al\u0131\u015fmada, lotus yapra\u011f\u0131 alkaloid konsantrasyonunun artmas\u0131yla h\u00fccrelerdeki HIF-1 \u03b1 ve anahtar glikolitik enzimler HK2 ve PKM2'nin mRNA seviyelerinin ve protein ifadesinin kademeli olarak azald\u0131\u011f\u0131 bulunmu\u015ftur. Bu nedenle, lotus yapra\u011f\u0131 alkaloidinin HIF-1 \u03b1 aktivitesini azaltarak HuCCT1 h\u00fccrelerinin glikoliz s\u00fcrecini etkileyebilece\u011fi tahmin edilmektedir.
\nHIF-1, h\u00fccrelerin d\u00fc\u015f\u00fck oksijenli veya hipoksik ortamlarda tepki verdi\u011fi ve iki alt birimden olu\u015fan bir t\u00fcr transkripsiyon fakt\u00f6r\u00fcd\u00fcr: HIF-1 \u03b1 ve HIF-1 \u03b2. HIF-1 \u03b1'n\u0131n prolin kal\u0131nt\u0131s\u0131 normoksik ko\u015fullar alt\u0131nda hidroksilasyona duyarl\u0131d\u0131r ve ayar molek\u00fcl\u00fcne (von Hippel Lindau, pVHL) ba\u011flan\u0131r, bu molek\u00fcl daha sonra ubikitinasyon yoluyla par\u00e7alan\u0131r. D\u00fc\u015f\u00fck oksijen ortam\u0131nda, prolil hidroksilaz alan\u0131 i\u00e7eren proteinlerin (PHD) aktivitesi azal\u0131r, bu da HIF-1 \u03b1'n\u0131n \u00f6nemli \u00f6l\u00e7\u00fcde birikmesine yol a\u00e7ar ve daha sonra HIF-1 \u03b2 ile bir dimer olu\u015fturmak \u00fczere \u00e7ekirde\u011fe g\u00f6\u00e7 eder. Dimer daha sonra HIF-1 hedef genlerinin transkripsiyonunu te\u015fvik etmek i\u00e7in hipoksik yan\u0131t elementine (HRE) ba\u011flan\u0131r. Buna ek olarak, HIF-1 \u03b1 oksijenden ba\u011f\u0131ms\u0131z bir \u015fekilde de aktive edilebilir, \u00f6rne\u011fin PI3K\/Akt\/mTOR sinyal kaskad\u0131 \u00f6karyotik translasyon ba\u015flatma fakt\u00f6r\u00fc 4E (eIF4E) ba\u011flay\u0131c\u0131 protein 1'in (4EBP1) b\u00fct\u00fcnl\u00fc\u011f\u00fcn\u00fc bozarak HIF-1 \u03b1'n\u0131n transkripsiyonunu ve translasyonunu yukar\u0131 do\u011fru d\u00fczenleyebilir. Baz\u0131 ara\u015ft\u0131rmac\u0131lar bu oksijenden ba\u011f\u0131ms\u0131z HIF-1 \u03b1 sinyalinin aktivasyon mekanizmas\u0131n\u0131 \"yalanc\u0131 hipoksi\" olarak adland\u0131rmaktad\u0131r. Bu \u00e7al\u0131\u015fmada, KEGG analizi, matrinin PI3K\/Akt sinyal yolunda \u00f6nemli bir art\u0131\u015fla birlikte ICC'nin potansiyel yollar\u0131 \u00fczerinde etkili oldu\u011funu ortaya koymu\u015ftur. \u0130mm\u00fcnoblotlama, matrinin HuCCT1 h\u00fccrelerinde mTOR ve 4EBP1 proteinlerinin fosforilasyon seviyelerini azaltabildi\u011fini ve genel p-AktTrr308 proteininin azalma e\u011filimi g\u00f6sterdi\u011fini ortaya koymu\u015ftur; bu da HIF-1 \u03b1 transkripsiyon ve translasyon seviyelerinin matrin taraf\u0131ndan a\u015fa\u011f\u0131 reg\u00fclasyonunun Akt\/mTOR\/4EBP1 sinyal yolunun inhibisyonu ile ili\u015fkili olabilece\u011fini d\u00fc\u015f\u00fcnd\u00fcrmektedir.<\/p>\n

\u00c7ok say\u0131da \u00e7al\u0131\u015fma, t\u00fcm\u00f6r h\u00fccrelerinin in vitro apoptozunu ind\u00fcklemenin, invazyon ve metastaz\u0131 inhibe etmenin ve farkl\u0131 d\u00f6ng\u00fclere bloke etmenin yan\u0131 s\u0131ra, lotus yapra\u011f\u0131 alkaloidlerinin \u00e7\u0131plak farelerde ektopik nakledilen t\u00fcm\u00f6rlerin b\u00fcy\u00fcmesini geciktirebilece\u011fini ve \u00f6nemli anti-t\u00fcm\u00f6r etkiler g\u00f6sterebilece\u011fini g\u00f6stermi\u015ftir. Ana mekanizma, lotus yapra\u011f\u0131 alkaloidleri taraf\u0131ndan h\u00fccre d\u00f6ng\u00fcs\u00fc ve apoptoz ile ilgili protein ifadesinin d\u00fczenlenmesi, spesifik genlerin do\u011frudan hedeflenmesi, PI3K Akt, Wnt\/\u03b2 - catenin, SOX2 Akt, STAT3 ve TLR4\/NF - \u03ba B gibi sinyal yollar\u0131n\u0131n inhibisyonu ile ilgilidir. Bu \u00e7al\u0131\u015fma ilk olarak lotus yapra\u011f\u0131 alkaloidlerinin, muhtemelen Akt\/mTOR\/4EBP1 sinyal yolu taraf\u0131ndan d\u00fczenlenen h\u00fccresel glikoliz s\u00fcrecini bask\u0131layarak intrahepatik kolanjiyokarsinom h\u00fccrelerinin \u00e7o\u011falmas\u0131n\u0131 engelledi\u011fini bulmu\u015ftur. Lotus yapra\u011f\u0131 alkaloidlerinin anti ICC mekanizmas\u0131n\u0131 ayd\u0131nlatmak ve lotus yapra\u011f\u0131 kaynaklar\u0131n\u0131n ve klinik uygulamalar\u0131n derinlemesine geli\u015ftirilmesi i\u00e7in teorik bir temel sa\u011flamak amac\u0131yla, ikisi aras\u0131ndaki i\u00e7sel mant\u0131ksal ili\u015fki ara\u015ft\u0131rman\u0131n bir sonraki ad\u0131m\u0131nda ara\u015ft\u0131r\u0131lacakt\u0131r.<\/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\/tr\/lotus-leaf-alkaloid-on-akt-mtor-4ebp1\/\" \/>\n<meta property=\"og:locale\" content=\"tr_TR\" \/>\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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