Photodynamic Therapy Mediated by Aloe-Emodin Inhibited Angiogenesis and Cell Metastasis Through Activating MAPK Signaling Pathway on HUVECs

Abstract

Photodynamic therapy is a clinically used, minimally invasive therapeutic procedure that involves the application of photosensitizers which can locate in target cells and so be irradiated at a corresponding wavelength. Laser light irradiation activation of photosensitizers generates free reactive oxygen species, which induces selective cytotoxic activity in target cells. Within recent years, aloe-emodin as a photosensitizer has been successfully applied in photodynamic therapy applications. Angiogenesis plays an important role in tumor growth and metastasis; thus, the development of a novel target treatment for angiogenesis is essential in order to improve treatment therapeutics for cancer treatment. An essential step in angiogenesis involves the formation of tube-like structures during matrix degradation, rearrangement, and apoptosis of endothelial cells. In the present study, we investigated the mechanisms of photocytotoxicity induced by aloe-emodin in human umbilical vein endothelial cells. Analysis of cell proliferation results noted a significant decrease in cultured cells which received various concentrations of aloe-emodin and photodynamic therapy–induced light doses. Additionally, mitochondrial mechanisms of apoptotic cell death were observed in aloe-emodin photodynamic therapy–treated cells, as tube formation assays noted angiogenesis suppression after treatment. The capacity of migration and invasion of human umbilical vein endothelial cells was measured using the transwell assay and demonstrated that aloe-emodin photodynamic therapy significantly inhibited the migration and invasion of human umbilical vein endothelial cells. The expression of p38, extracellular signal-regulated kinase, the c-Jun N-terminal kinases, and vascular endothelial growth factor suggested that the cellular metastasis was related to mitogen-activated protein kinase signal pathway. Furthermore, disorganization of F action cytoskeleton components was observed after aloe-emodin photodynamic therapy. Overall, the findings from this study suggest that aloe-emodin photodynamic therapy inhibited angiogenesis and cellular metastasis in human umbilical vein endothelial cells by activating the mitogen-activated protein kinase apoptotic signaling cell death pathway.

<p>miR-106b promotes proliferation and invasion by targeting Capicua through MAPK signaling in renal carcinoma cancer</p>

“…The MAPK pathway, known as a cascade of protein kinases, is closely associated with the tumorigenesis in multiple malignancies. [50][51][52] The activation of MAPK pathway could stimulate various oncogenic systems including EMT, which transferred epithelial characteristics into mesenchymal phenotype, finally leading tumors getting migratory and invasive features. 53 Consistently, our study also demonstrated that overexpression of CIC inhibited the proliferative and invasion of RCC cells in vivo through suppressing the activation of MAPK pathway, which indicated that MAPK pathway might be involved in the regulation of miR-106b/CIC axis during proliferation and metastasis in RCC progression.…”

MPPa-PDT suppresses breast tumor migration/invasion by inhibiting Akt-NF-κB-dependent MMP-9 expression via ROS

“…Photodynamic therapy (PDT), as a valid therapy modality for multiple solid tumors, is minimally invasive and innoxious and possesses selective cytotoxicity for targeted cells [15]. It is based on photosensitizers and laser light with a specific wavelength, causing the production of reactive oxygen species (ROS) and inducing tumor cell apoptosis/necrosis [16].…”

Aloe emodin: From antito pro-tumor action

“…Mention processes are connected with the activation of p38, ERK, but not JNK, while the expression of vascular endothelial growth factor was diminished upon the treatment. In addition, AE-PDT altered the organization of F actin cytoskeleton [52].…”