Torilis japonica 95% Ethanol extraction compound induces apoptosis and inhibits metastasis via regulated intracellular signaling pathways

다국어 초록 (Multilingual Abstract)

Induced apoptosis and anti-abnormal metastasis in cancer cells is a therapeutic strategy for the treatment of cancer. In this study, I investigated the regulatory mechanism of Torilis japonica 95% ethanol extract-induced apoptosis through the AMPK/p38 MAPkinase signaling pathway and suppressed abnormal metastasis by epidermal-mesenchymal transition (EMT) through regulated EGFR signaling pathways.
My results showed that TJE induced apoptosis through generated intracellular Reactive Oxygen Species (ROS), and it responsible for depressed mitochondria membrane potential. And not only in vitro experiment, but TJE suppressed tumor growth and induced apoptosis in in vivo experiment.
In addition, treatment with TJE along with stimulation by EGF prevented changes in cell morphology, mobility, expression of actin polarization proteins and EMT markers. Using specific inhibitors and siEGFR, it was demonstrated that TJE suppressed EMT through EGFR inactivation and regulation of its downstream signaling pathways.
I suggest that TJE is a new potential multi-target cancer prevention reagent for induced apoptosis through generated intracellular ROS and EGFR-targeted anti-abnormal metastasis.

목차 (Table of Contents)

• I. Introduction 1
• II. Materials and Methods 6
• III. Result 16
• Chapter I. Torilis japonica Ethanol extraction compound (TJE) induces apoptosis by increasing the generation of intracellular ROS 16
• 1-1. TJE generates intracellular ROS in HCT116 colon cancer cells 17
• 1-2. TJE suppresses cancer cell proliferation and induces apoptosis 18
• 1-3. TJE regulates the expression of p53 and AMPK, p38 activation 20
• 1-4. TJE induces apoptosis via depressed mitochondria membrane potential 21
• 1-5. TJE modulates the protein signaling pathways and mitochondria membrane potential through the generation of intracellular ROS 23
• 1-6. TJE regulated cytochrome C translocation to cytoplasm 27
• 1-7. TJE induced apoptosis via AMPK/p38 MAPkinase signaling pathway 29
• 1-8. Induced apoptosis was p53 independent manner 31
• 1-9. TJE induced cell death through regulated intracellular signaling pathways in HCT116 Xenograft model 32
• Chapter II. TJE, a new potential EMT suppressor agent by regulation of EGFR signaling pathways 35
• 2-1. TJE reduces cell proliferation in MCF-7 breast cancer cells 36
• 2-2. TJE suppresses cell migration and invasion through regulation of EGF-induced EMT 37
• 2-3. TJE regulates EGFR activation and its downstream proteins 39
• 2-4. TJE regulates expression of actin polarization related proteins and EMT marker genes 40
• 2-5. Regulation of VEGF, p-VASP, and EMT markers by TJE treatment through control of EGFR activation 42
• 2-6. TJE regulates actin polarization and cadherin proteins expression by controlling EGFR activation 44
• IV. Discussion 46
• V. Reference 50
• VI. Abstract 61