euxanthone and Lung-Neoplasms

Osteosarcoma (OS) is one of the most common malignancies of bone. This study was aimed to explore the anti-metastatic effect of euxanthone on OS. Adhesion assay and Transwell assay were used to examine the effect of euxanthone on adhesion, migration and invasion of OS cells. COX-2-over-expressing plasmid was applied to transfect OS cells to assess whether COX-2 affects the anti-metastatic function of euxanthone. PDCD4 knockdown and miR-21 mimic were applied to assess whether euxanthone suppresses the transactivation of c-jun via modulating miR-21-PDCD4 signaling. The effect of euxanthone in vivo was also examined by lung metastasis assay. Euxanthone, a xanthone derivative extracted from Polygala caudata, has been found to exhibit anti-neoplastic activities. In present study, our results showed that euxanthone suppressed cell adhesion, migration, and invasion in OS cells. Our experimental data also showed that repression of COX-2 by euxanthone mediated its anti-metastatic activities. Moreover, our findings revealed that euxanthone modulated the COX-2 expression through the miR-21/PDCD4/c-jun signaling pathway. The anti-metastatic activities of euxanthone were also validated in a pulmonary metastasis model. Taken together, our results highlighted the potential of euxanthone to be used in the treatment of OS. Anat Rec, 302:1399-1408, 2019. © 2018 Wiley Periodicals, Inc.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Bone Neoplasms; Cell Adhesion; Cell Movement; Cell Proliferation; Cyclooxygenase 2; Gene Expression Regulation, Neoplastic; Humans; JNK Mitogen-Activated Protein Kinases; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Neoplasm Invasiveness; Osteosarcoma; RNA-Binding Proteins; Signal Transduction; Tumor Cells, Cultured; Xanthones; Xenograft Model Antitumor Assays

Colorectal cancer (CRC) accounts for over 600,000 deaths annually worldwide. Euxanthone is a flavonoid compound extracted from Polygala caudata, with documented anti-neoplastic actions. The current study aimed to determine the therapeutic potential of euxanthone in CRC.. Cell Counting Kit-8 (CCK-8) assay was used to analyze the effect of euxanthone on the cell viability, and apoptosis was detected by the TUNEL assay. The in vitro migratory capacity was determined by wound healing and the invasiveness was assessed by Transwell assay. Western blotting was used to determine the level of relevant proteins. Furthermore, a CRC xenograft murine model was used to analyze the therapeutic efficacy of euxanthone in vivo. Isobaric tags for relative and absolute quantification (iTRAQ) was then performed to identify the potential targets of euxanthone. To validate the role of cancerous inhibitor of PP2A (CIP2A) in the anti-cancer effects of euxanthone, plasmid overexpressing CIP2A and shRNA targeting CIP2A were used in in vitro assays.. Euxanthone decreased cell viability and increased apoptosis in CRC cells, in addition to restraining migration, invasion and EMT. Similarly, euxanthone also effectively suppressed tumor growth and pulmonary metastasis in vivo. iTRAQ analysis identified CIP2A as the primary target responsible for the anticancer effects of euxanthone. The mediatory role of CIP2A was validated when the anticancer activity of euxanthone was significantly blocked by CIP2A overexpression, while CIP2A knockdown sensitized the CRC cells to euxanthone.. Euxanthone exerts anti-cancer effects in vitro and in vivo in CRC by targeting CIP2A/PP2A signaling.

Topics: Animals; Apoptosis; Autoantigens; Cell Proliferation; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Humans; Intracellular Signaling Peptides and Proteins; Lung Neoplasms; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Protein Phosphatase 2; Tumor Cells, Cultured; Xanthones; Xenograft Model Antitumor Assays