Camptothecin suppresses expression of matrix metalloproteinase-9 and vascular endothelial growth factor in DU145 cells through PI3K/Akt-mediated inhibition of NF-κB activity and Nrf2-dependent induction of HO-1 expression |
| |
| Affiliation: | 1. Department of Pharmacognosy and Phytochemistry, Medical University of Silesia in Katowice, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Jagiellońska 4, 41-200 Sosnowiec, Poland;2. Department of Statistics, School of Pharmacy with Division of Laboratory Medicine, Medical University of Silesia, 30 Ostrogórska Street, 41-200 Sosnowiec, Poland;3. Clinic of Infertility Treatment, Gynecology and Obstetrics, Bocian Clinic in Katowice, Dąbrówki 13, 40-081 Katowice, Poland;4. Institute of Building Materials and Structures, Faculty of Civil Engineering, Cracow University of Technology, 31-155 Cracow, Poland;1. The Key Laboratory of the Inorganic Molecule-Based Chemistry of Liaoning Province and Laboratory of Coordination Chemistry, Shenyang University of Chemical Technology, Shenyang 110142, China;2. Life Engineering College, Shenyang Institute of Technology, Fushun 113122, China;3. Department of Chemistry, Nankai University, Tianjin 300007,China;4. Institute of Organic Chemistry “C.D. Nenitescu”, Romanian Academy, 060023 Bucharest, Romania;1. Kuopio University Hospital, Department of Surgery, FI-70029 KYS, Finland;2. Department of Surgery, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland;3. Kuopio University Hospital, Department of Clinical Pathology, FI-70029 KYS, Finland;4. Department of Pathology and Forensic Medicine, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, FI-70211 Kuopio, Finland |
| |
| Abstract: | Though camptothecin (CPT) possesses potent anti-inflammatory, immunomodulatory, anticancerous, and antiproliferative effects, little is known about the mechanism by which CPT regulates the expression of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF). Therefore, the current study aimed to investigate the effects of CPT on the expression of MMP-9 and VEGF, which are important factors for the invasion of tumors. In vitro application of CPT resulted in a slight inhibition of cell proliferation and a significant reduction in the matrigel invasion of DU145 cells. Treatment with CPT also downregulated phorbol-12-myristate-13-acetate (PMA)- and tumor necrosis factor-α (TNF-α)-induced MMP-9 and VEGF expression by inhibiting nuclear factor-κB (NF-κB) activity. Downregulation of phosphoinositide 3-kinase (PI3K)/Akt phosphorylation in response to CPT was revealed as an upstream pathway regulating the expression of MMP-9 and VEGF accompanying the inhibition of NF-κB activity. We further confirmed that CPT inhibits PMA-induced MMP-9 and VEGF expression by upregulating nuclear factor-erythroid related factor-2 (Nrf2)-mediated heme oxygenase-1 (HO-1) induction. Taken together, these data indicate that CPT inhibits the invasion of cancer cells accompanied by suppression of MMP-9 and VEGF production by suppressing the PI3K/Akt-mediated NF-κB pathway and enhancing the Nrf2-dependent HO-1 pathway, suggesting that CPT may be a good candidate to inhibit MMP-9 and VEGF expression. |
| |
| Keywords: | Camptothecin Matrix metalloproteinase-9 Vascular endothelial growth factor Nuclear factor-κB Heme oxygenase-1 Nuclear erythroid 2-related factor-2 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
