Al-Suede, Fouad Saleih Resq
(2016)
Investigation Of Molecular Mechanisms Underlying The Anti-Tumor And Anti-Angiogenic Activities Of Orthosiphon Stamineus Towards Colorectal Cancer.
PhD thesis, Universiti Sains Malaysia.
Abstract
Teh Orthosiphon stamineus Benth. (Lamiaceae) digunakan secara meluas dalam perubatan tradisional. Kajian terbaru menunjukkan bahawa 50% ekstrak ethanolik daripada Orthosiphon stamineus (EOS) dan sebatian aktif, asid rosmarinik (RA), memaparkan kesan-kesan anti-angiogenik, anti-radang dan anti-tumor yang ketara dalam pelbagai model eksperimen. Walau bagaimanapun, mekanisme yang mendasari sifat-sifat ini tidak dinilai dengan sepenuhnya. Kajian yang dijalankan ini bertujuan untuk menilaikan lagi mekanisme molekul yang mendasari anti-tumor dan anti-angiogenik. Dalam model eksperimen penghijrahan, perkembangan dan pembentukan tiub, cerakin kedua-dua EOS dan RA aktif menyebabkan perencatan ketara terhadap fungsi sel endothelial manusia (HUVECs) yang penting bagi merangsang proses angiogenesis. Dalam kedua-dua kajian in vitro dan in vivo, penindasan besar neovaskularisasi dalam model aorta tikus, CAM dan plug matrigel juga diperhatikan. Kajian cerakin multipleks menunjukkan pengurangan faktor pertumbuhan utama bagi lata pro-angiogenik dan perkembangan tumor iaitu faktor pertumbuhan endothelial vaskular (VEGF), faktor pertumbuhan fibroblast asas (b-FGF), transformasi faktor pertumbuhan transformasi (TGF-α), faktor nekrosis tumor (TNF-β) dan interleukin-1, 2, 7.
Orthosiphon stamineus Benth. (Lamiaceae) tea is widely consumed traditionally for its vast medicinal value. Recent studies revealed that 50% ethanolic extract of Orthosiphon stamineus (EOS) and its active compound, rosmarinic acid (RA), displayed significant anti-angiogenic, anti-inflammatory and anti-tumor effects in various experimental models. However, the mechanisms underlying these properties have not been fully evaluated. The present work aims to further evaluate the molecular mechanisms underlying its anti-tumour and anti-angiogenic properties. In migration, proliferation and tube formation assay, both EOS and its active RA caused significant inhibition of human endothelial cell (HUVECs) functions crucial for promotion of angiogenesis. Both in vitro and in vivo studies revealed significant suppression of neovascularisation in rat aortic ring, CAM and matrigel plug. Multiplex array studies showed reduction of key growth factors for pro-angiogenic cascade and tumor development i.e. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), transforming growth factor alpha (TGF-α), tumor necrosis factor (TNF-β) and interleukin-1, 2, 7.
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