{"id":7514,"date":"2024-08-06T20:17:59","date_gmt":"2024-08-06T20:17:59","guid":{"rendered":"https:\/\/longchangextracts.com\/?p=7514"},"modified":"2024-08-06T20:17:59","modified_gmt":"2024-08-06T20:17:59","slug":"kaempferol","status":"publish","type":"post","link":"https:\/\/longchangextracts.com\/hu\/kaempferol\/","title":{"rendered":"A kaempferol mechanizmusa a tripla negat\u00edv eml\u0151r\u00e1ksejtek apopt\u00f3zis\u00e1nak kiv\u00e1lt\u00e1sa a mitokondri\u00e1lis apopt\u00f3zis \u00fatvonalon kereszt\u00fcl"},"content":{"rendered":"

A kaempferol mechanizmusa a tripla negat\u00edv eml\u0151r\u00e1ksejtek apopt\u00f3zis\u00e1nak kiv\u00e1lt\u00e1sa a mitokondri\u00e1lis apopt\u00f3zis \u00fatvonalon kereszt\u00fcl
\nA h\u00e1rmas negat\u00edv eml\u0151r\u00e1k (TNBC), mint az eml\u0151r\u00e1k egy speci\u00e1lis alt\u00edpusa, az eml\u0151r\u00e1k teljes sz\u00e1m\u00e1nak 15%~20% %-\u00e1t teszi ki. Klinikai jellemz\u0151i a r\u00f6vid teljes t\u00fal\u00e9l\u00e9si id\u0151, a magas malignit\u00e1s, az er\u0151s inv\u00e1zi\u00f3, a magas korai ki\u00fajul\u00e1si ar\u00e1ny stb. Az \u00e1tt\u00e9tk\u00e9pz\u0151d\u00e9s ut\u00e1n a betegek medi\u00e1n t\u00fal\u00e9l\u00e9si ideje mind\u00f6ssze 10~13 h\u00f3nap. A TNBC endokrin ter\u00e1pi\u00e1ra \u00e9s c\u00e9lzott ter\u00e1pi\u00e1ra val\u00f3 \u00e9rz\u00e9ketlens\u00e9ge miatt a kemoter\u00e1pia a f\u0151 kezel\u00e9si m\u00f3dszer. A gy\u00f3gyszerrezisztencia \u00e9s a kezel\u00e9ssel kapcsolatos mell\u00e9khat\u00e1sok azonban tov\u00e1bbra is aggodalomra adnak okot. Az elm\u00falt \u00e9vekben egyre ink\u00e1bb fel\u00e9rt\u00e9kel\u0151d\u00f6tt a hagyom\u00e1nyos k\u00ednai orvosl\u00e1s szerepe a TNBC megel\u0151z\u00e9s\u00e9ben \u00e9s kezel\u00e9s\u00e9ben, k\u00f6sz\u00f6nhet\u0151en egyed\u00fcl\u00e1ll\u00f3 elm\u00e9leti rendszer\u00e9nek \u00e9s az egy\u00e9nre szabott kezel\u00e9si tervekben val\u00f3 j\u00e1rtass\u00e1g\u00e1nak. Kutat\u00f3csoportunk kor\u00e1bbi kutat\u00e1sai sor\u00e1n meg\u00e1llap\u00edtotta, hogy a Chaihu Guizhi f\u0151zet hozz\u00e1ad\u00e1sa \u00e9s cs\u00f6kkent\u00e9se kapecitabinnal kombin\u00e1lva g\u00e1tolja a tripla negat\u00edv eml\u0151r\u00e1k szubkut\u00e1n transzplant\u00e1lt tumorj\u00e1nak n\u00f6veked\u00e9s\u00e9t meztelen egerekben. A h\u00e1l\u00f3zati farmakol\u00f3giai m\u00f3dszerrel v\u00e9gzett tov\u00e1bbi elemz\u00e9s kimutatta, hogy a kaempferol (KA) fontos hat\u00e9kony \u00f6sszetev\u0151je a Chaihu Guizhi Decoction hozz\u00e1ad\u00e1s\u00e1nak \u00e9s cs\u00f6kkent\u00e9s\u00e9nek, ami k\u00eds\u00e9rleti alapot biztos\u00edt sz\u00e1munkra a kaempferol h\u00e1rmas negat\u00edv eml\u0151r\u00e1k kezel\u00e9s\u00e9re.
\nA kaempferol egy flavonoid vegy\u00fclet, amely sz\u00e9les k\u00f6rben megtal\u00e1lhat\u00f3 a z\u00f6lds\u00e9gekben, gy\u00fcm\u00f6lcs\u00f6kben \u00e9s a hagyom\u00e1nyos k\u00ednai orvosl\u00e1sban. K\u00fcl\u00f6nb\u00f6z\u0151 hat\u00e1sai vannak, p\u00e9ld\u00e1ul r\u00e1kellenes, gyullad\u00e1scs\u00f6kkent\u0151, antioxid\u00e1ns \u00e9s v\u00edrusellenes. A sejtek apopt\u00f3zis\u00e1nak kiv\u00e1lt\u00e1s\u00e1val, a sejtciklus szab\u00e1lyoz\u00e1s\u00e1val, az angiogenezis \u00e9s a tumoros \u00e1tt\u00e9tk\u00e9pz\u0151d\u00e9s g\u00e1tl\u00e1s\u00e1val g\u00e1tolhatja a tumorsejtek prolifer\u00e1ci\u00f3j\u00e1t \u00e9s inv\u00e1zi\u00f3j\u00e1t. A kutat\u00e1sok meg\u00e1llap\u00edtott\u00e1k, hogy a KA a MEK-MAPK aktiv\u00e1l\u00e1s\u00e1val n\u00f6veked\u00e9si g\u00e1tl\u00e1st \u00e9s apopt\u00f3zist induk\u00e1l a t\u00fcd\u0151r\u00e1ksejtekben. In vitro \u00e9s in vivo a KA g\u00e1tolja az AKT\/PI3K \u00e9s ERK \u00fatvonalakat, aktiv\u00e1lja a mitokondri\u00e1lis apopt\u00f3zis \u00fatvonalat, \u00e9s n\u00f6veli a t\u00fcd\u0151r\u00e1ksejtek sug\u00e1rz\u00e1s \u00e1ltali elpuszt\u00edt\u00e1s\u00e1t. Vastagb\u00e9lr\u00e1kban a KA helyre\u00e1ll\u00edtja a r\u00e9skapcsolatok intercellul\u00e1ris kommunik\u00e1ci\u00f3j\u00e1t az\u00e1ltal, hogy fokozza a csom\u00f3ponti feh\u00e9rje 43 expresszi\u00f3j\u00e1t \u00e9s foszforil\u00e1ci\u00f3j\u00e1t a vastagb\u00e9lr\u00e1ksejtekben, ez\u00e1ltal sejt apopt\u00f3zist induk\u00e1l. A KA a PI3K\/AKT \u00e9s a hTERT \u00fatvonalak downregul\u00e1l\u00e1s\u00e1val apopt\u00f3zist \u00e9s \u00f6reged\u00e9st is el\u0151id\u00e9zhet hum\u00e1n m\u00e9hnyakr\u00e1ksejtekben. Mellr\u00e1kban arr\u00f3l sz\u00e1moltak be, hogy a KA k\u00fcl\u00f6nb\u00f6z\u0151 mechanizmusokon kereszt\u00fcl tumorellenes szerepet j\u00e1tszik. A KA g\u00e1tolhatja az eml\u0151r\u00e1ksejtek inv\u00e1zi\u00f3j\u00e1t a PKC \u03b4\/MAPK\/AP-1 kaszk\u00e1d expresszi\u00f3j\u00e1nak \u00e9s aktivit\u00e1s\u00e1nak, majd a m\u00e1trix metalloprotein\u00e1z-9 (MMP-9) g\u00e1tl\u00e1s\u00e1val. Li \u00e9s munkat\u00e1rsai meg\u00e1llap\u00edtott\u00e1k, hogy a KA a Notch1 feh\u00e9rje szab\u00e1lyoz\u00e1s\u00e1val g\u00e1tolhatja az eml\u0151r\u00e1k SK-BR-3 sejtek prolifer\u00e1ci\u00f3j\u00e1t. Ezenk\u00edv\u00fcl a KA g\u00e1tolni tudja az MCF-7 eml\u0151r\u00e1ksejtek trikloz\u00e1n \u00e1ltal induk\u00e1lt epiteli\u00e1lis-mesenchym\u00e1lis transzform\u00e1ci\u00f3j\u00e1t (EMT) \u00e9s metaszt\u00e1zissal kapcsolatos viselked\u00e9s\u00e9t is. B\u00e1r a KA r\u00e1kellenes hat\u00e1s\u00e1t sz\u00e1mos tumorban meger\u0151s\u00edtett\u00e9k, nincs jelent\u00e9s arr\u00f3l, hogy a KA k\u00e9pes-e apopt\u00f3zist induk\u00e1lni a tripla negat\u00edv eml\u0151r\u00e1ksejtekben \u00e9s annak molekul\u00e1ris mechanizmus\u00e1r\u00f3l. Ez a tanulm\u00e1ny az MDA-MB-231 hum\u00e1n TNBC-sejtet veszi kutat\u00e1si t\u00e1rgynak, hogy megfigyelje a kaempferol hat\u00e1s\u00e1t az MDA-MB-231 sejt apopt\u00f3zis\u00e1ra, \u00e9s hogy a lehets\u00e9ges mechanizmus kapcsol\u00f3dik-e a mitokondri\u00e1lis apopt\u00f3zis \u00fatvonal\u00e1hoz, hogy elm\u00e9leti alapot \u00e9s k\u00eds\u00e9rleti alapot biztos\u00edtson a kaempferol klinikai alkalmaz\u00e1s\u00e1hoz a h\u00e1rmas negat\u00edv eml\u0151r\u00e1k kezel\u00e9s\u00e9ben.<\/p>\n

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\nA kaempferol, mint a k\u00fcl\u00f6nb\u00f6z\u0151 n\u00f6v\u00e9nyekben sz\u00e9les k\u00f6rben jelen l\u00e9v\u0151 poliol-hidroxi-flavonoid vegy\u00fclet, nemcsak hat\u00e9konyan g\u00e1tolja a tumorsejtek n\u00f6veked\u00e9s\u00e9t \u00e9s apopt\u00f3zist induk\u00e1lhat, hanem fenntartja a norm\u00e1l sejtek n\u00f6veked\u00e9si vitalit\u00e1s\u00e1t is. Chen \u00e9s munkat\u00e1rsai meg\u00e1llap\u00edtott\u00e1k, hogy a KA k\u00e9pes a prosztatar\u00e1k sejtciklus-meg\u00e1ll\u00e1st induk\u00e1lni, g\u00e1tolja a sejtprolifer\u00e1ci\u00f3t, \u00e9s nincs hat\u00e1sa a norm\u00e1l emberi fityma fibroblasztok (HFF) \u00e9letk\u00e9pess\u00e9g\u00e9re, ami azt jelzi, hogy a KA j\u00f3 daganatellenes hat\u00e9konys\u00e1ggal \u00e9s alacsony toxicit\u00e1ssal rendelkezik. Tu \u00e9s munkat\u00e1rsai meg\u00e1llap\u00edtott\u00e1k, hogy a KA hat\u00e9konyan k\u00e9pes g\u00e1tolni a hum\u00e1n m\u00e9hnyakr\u00e1ksejtek prolifer\u00e1ci\u00f3j\u00e1t \u00e9s metaszt\u00e1zis\u00e1t, m\u00edg a karcinoembri\u00f3s vesesejtekre \u00e9s a norm\u00e1l m\u00e1jsejtekre gyakorolt citotoxikus hat\u00e1sa viszonylag kicsi, ami azt jelzi, hogy a KA magas r\u00e1ksejt-c\u00e9lz\u00f3 k\u00e9pess\u00e9ggel rendelkezik. Kev\u00e9s tanulm\u00e1ny sz\u00fcletett a KA-r\u00f3l a tripla negat\u00edv eml\u0151r\u00e1ksejtekben. Ez\u00e9rt ez a tanulm\u00e1ny meger\u0151s\u00edtette, hogy a KA jelent\u0151sen g\u00e1tolja a TNBC sejtek prolifer\u00e1ci\u00f3j\u00e1t \u00e9s el\u0151seg\u00edti a sejtek apopt\u00f3zis\u00e1t az MDA-MB-231 \u00e9s MCF-10A sejteken v\u00e9gzett in vitro vizsg\u00e1latokon kereszt\u00fcl, de nincs hat\u00e1sa a norm\u00e1l eml\u0151 epiteli\u00e1lis MCF-10A sejtek prolifer\u00e1ci\u00f3j\u00e1ra.
\nEnnek alapj\u00e1n ez a k\u00eds\u00e9rlet tov\u00e1bb vizsg\u00e1lja a KA apopt\u00f3zis indukci\u00f3s mechanizmus\u00e1t az MDA-MB-231 sejteken. Jelenleg a kutat\u00e1sok azt tal\u00e1lt\u00e1k, hogy a sejt apopt\u00f3zis els\u0151sorban h\u00e1rom \u00fatvonalat foglal mag\u00e1ban a kezdem\u00e9nyez\u00e9si folyamat alapj\u00e1n: mitokondri\u00e1lis \u00fatvonal, hal\u00e1lreceptor \u00fatvonal \u00e9s endoplazmatikus retikulum \u00fatvonal, \u00e9s a mitokondri\u00e1lis \u00fatvonal fontos szerepet j\u00e1tszik a sejt apopt\u00f3zis k\u00f6zvet\u00edt\u00e9s\u00e9ben. A mitokondri\u00e1lis membr\u00e1npotenci\u00e1l az egyik legjobb mutat\u00f3, amely a mitokondri\u00e1lis bels\u0151 membr\u00e1n \u00e1tereszt\u0151k\u00e9pess\u00e9g\u00e9t t\u00fckr\u00f6zi. A mitokondri\u00e1lis membr\u00e1npotenci\u00e1l cs\u00f6kken\u00e9s\u00e9t tekintik a sejt apopt\u00f3zis kaszk\u00e1dreakci\u00f3j\u00e1nak legkor\u00e1bbi esem\u00e9ny\u00e9nek. Amint a mitokondri\u00e1lis membr\u00e1npotenci\u00e1l \u00f6sszeomlik, a sejt apopt\u00f3zisa visszaford\u00edthatatlann\u00e1 v\u00e1lik. Feng \u00e9s munkat\u00e1rsai izol\u00e1ltak egy arabinogalakt\u00e1nt az Artemisia scoparia-b\u00f3l, amely k\u00e9pes elpuszt\u00edtani a hum\u00e1n orrgarati karcin\u00f3ma CNE-2 sejteket az\u00e1ltal, hogy mitokondri\u00e1lis membr\u00e1npotenci\u00e1l-veszt\u00e9st okoz. Ez a tanulm\u00e1ny meg\u00e1llap\u00edtotta, hogy a KA hat\u00e1s\u00e1ra cs\u00f6kken a mitokondri\u00e1lis membr\u00e1npotenci\u00e1l az MDA-MB-231 sejtekben, ami arra utal, hogy a kaempferol egyik mechanizmusa, amellyel g\u00e1tolja a sejtek prolifer\u00e1ci\u00f3j\u00e1t \u00e9s el\u0151seg\u00edti az apopt\u00f3zist, a mitokondri\u00e1lis k\u00f6zvet\u00edt\u00e9s\u0171 apoptotikus \u00fatvonalon kereszt\u00fcl val\u00f3sulhat meg. A KA \u00e1ltal kiv\u00e1ltott MDA-MB-231 sejtek apopt\u00f3zisa \u00e9s a mitokondri\u00e1lis apopt\u00f3zis jel\u00e1tviteli \u00fatvonal k\u00f6z\u00f6tti kapcsolat tov\u00e1bbi vizsg\u00e1lata \u00e9rdek\u00e9ben ez a tanulm\u00e1ny kimutatta a Bcl-2, Bax, CytC, Cyclin D1 expresszi\u00f3j\u00e1t, valamint a Caspase-3 \u00e9s Caspase-9 aktivit\u00e1s\u00e1t.<\/p>\n

A Bcl-2 feh\u00e9rjecsal\u00e1dhoz tartozik a Bcl-2 antiapoptotikus feh\u00e9rje \u00e9s a Bax proapoptotikus feh\u00e9rje. A mitokondri\u00e1lis k\u00fcls\u0151 membr\u00e1n integrit\u00e1s\u00e1nak szab\u00e1lyoz\u00f3ik\u00e9nt fontos szerepet j\u00e1tszanak a mitokondri\u00e1lis apopt\u00f3zis \u00fatj\u00e1nak szab\u00e1lyoz\u00e1s\u00e1ban. Az apoptotikus jel be\u00e9rkez\u00e9se ut\u00e1n a citoplazm\u00e1ban l\u00e9v\u0151 Bax transzlok\u00e1l\u00f3dik a mitokondriumba, \u00e9s az antiapoptotikus feh\u00e9rje, a Bcl-2 ir\u00e1ny\u00edtja a citokr\u00f3m C felszabadul\u00e1s\u00e1t a mitokondriumb\u00f3l, el\u0151seg\u00edtve a kaszp\u00e1z-9 prekurzor \u00f6naktiv\u00e1l\u00f3d\u00e1s\u00e1t. Az aktiv\u00e1lt kaszp\u00e1z-9 aktiv\u00e1lja a kaszp\u00e1z-3-at, ami v\u00e9g\u00fcl a sejt apopt\u00f3zis\u00e1hoz vezet. Liu \u00e9s munkat\u00e1rsai meg\u00e1llap\u00edtott\u00e1k, hogy a KA g\u00e1tolja az emberi epeh\u00f3lyagr\u00e1ksejtek prolifer\u00e1ci\u00f3j\u00e1t, \u00e9s a mitokondri\u00e1lis apopt\u00f3zis \u00fatvonal\u00e1n kereszt\u00fcl apopt\u00f3zist induk\u00e1l. Ebben a vizsg\u00e1latban megfigyelt\u00fck, hogy a KA n\u00f6velte a Bax expresszi\u00f3j\u00e1t \u00e9s cs\u00f6kkentette a Bcl-2 expresszi\u00f3j\u00e1t az MDA-MB-231 sejtekben, el\u0151seg\u00edtve a CytC citoplazm\u00e1ba t\u00f6rt\u00e9n\u0151 felszabadul\u00e1s\u00e1t a mitokondri\u00e1lis apopt\u00f3zis \u00fatvonalon kereszt\u00fcl, ami fokozott expresszi\u00f3t eredm\u00e9nyezett. Ezzel egyidej\u0171leg a mitokondri\u00e1lis membr\u00e1n permeabilit\u00e1sa megn\u0151, a membr\u00e1npotenci\u00e1l cs\u00f6kken, preapoptotikus faktorok szabadulnak fel, kiv\u00e1ltva a kaszp\u00e1z-3 \u00e9s kaszp\u00e1z-9 downstream aktiv\u00e1l\u00f3d\u00e1s\u00e1t, ami v\u00e9g\u00fcl a sejt apopt\u00f3zis\u00e1hoz vezet. Ezenk\u00edv\u00fcl az apopt\u00f3zis szorosan \u00f6sszef\u00fcgg a rendellenes sejtburj\u00e1nz\u00e1ssal, \u00e9s a sejtburj\u00e1nz\u00e1s f\u0151 oka a rendellenes sejtciklus. A ciklin D1, mint a sejtciklus fontos szab\u00e1lyoz\u00f3 feh\u00e9rj\u00e9je, el\u0151seg\u00edtheti a sejtek G1 f\u00e1zisb\u00f3l az S f\u00e1zisba val\u00f3 \u00e1tmenet\u00e9t, felgyors\u00edthatja a sejtciklus folyamat\u00e1t, \u00e9s felszab\u00e1lyoz\u00e1sa k\u00f3ros sejtprolifer\u00e1ci\u00f3t okozhat, v\u00e1ltoz\u00e1sokat id\u00e9zhet el\u0151 a mitokondri\u00e1lis membr\u00e1npotenci\u00e1lban, \u00e9s tumor kialakul\u00e1s\u00e1hoz vezethet. A k\u00eds\u00e9rlet eredm\u00e9nyei azt mutatj\u00e1k, hogy a KA k\u00e9pes lefel\u00e9 szab\u00e1lyozni az apopt\u00f3zissal kapcsolatos feh\u00e9rj\u00e9k, a Cyclin D1 \u00e9s a Bcl-2 expresszi\u00f3j\u00e1t az MDA-MB-231 sejtekben, cs\u00f6kkenti a mitokondri\u00e1lis membr\u00e1npotenci\u00e1lt, g\u00e1tolja a sejtprolifer\u00e1ci\u00f3t \u00e9s el\u0151seg\u00edti a sejtek apopt\u00f3zis\u00e1t.<\/p>\n

\u00d6sszefoglalva, ez a tanulm\u00e1ny tiszt\u00e1zta a kaempferol r\u00e1kellenes hat\u00e1s\u00e1t a tripla negat\u00edv eml\u0151r\u00e1ksejtekre in vitro, \u00e9s bizonyos biztons\u00e1ggal rendelkezik, \u00e9s tiszt\u00e1zta a KA mechanizmus\u00e1t, amely az MDA-MB-231 sejtek apopt\u00f3zis\u00e1t induk\u00e1lja a mitokondri\u00e1lis apopt\u00f3zis jel\u00fatj\u00e1n kereszt\u00fcl. K\u00e9s\u0151bb a KA TNBC-re gyakorolt g\u00e1tl\u00f3 hat\u00e1sa in vivo k\u00eds\u00e9rletekkel tov\u00e1bb tanulm\u00e1nyozhat\u00f3, ami k\u00eds\u00e9rleti alapot biztos\u00edt a KA fejleszt\u00e9s\u00e9hez \u00e9s klinikai alkalmaz\u00e1s\u00e1hoz.<\/p>","protected":false},"excerpt":{"rendered":"

The mechanism of kaempferol inducing apoptosis of triple negative breast cancer cells through mitochondrial apoptosis pathway Triple negative breast cancer (TNBC), as a special subtype of breast cancer, accounts for 15%~20% of the total number of breast cancer. It has the clinical characteristics of short overall survival period, high malignancy, strong invasion, high early recurrence […]<\/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":"\nThe mechanism of kaempferol inducing apoptosis of triple negative breast cancer cells through mitochondrial apoptosis pathway - 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\/kaempferol\/\" \/>\n<meta property=\"og:locale\" content=\"hu_HU\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The mechanism of kaempferol inducing apoptosis of triple negative breast cancer cells through mitochondrial apoptosis pathway - China Chemical Manufacturer\" \/>\n<meta property=\"og:description\" content=\"The mechanism of kaempferol inducing apoptosis of triple negative breast cancer cells through mitochondrial apoptosis pathway Triple negative breast cancer (TNBC), as a special subtype of breast cancer, accounts for 15%~20% of the total number of breast cancer. 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