Celastrol negatively regulates cell invasion and migration ability of human osteosarcoma via downregulation of the PI3K/Akt/NF-κB signaling pathway in vitro

Abstract

Abstract. Osteosarcoma (OS) is a primary malignant tumor of the bone, with a tendency to metastasize early. Despite the advances in treatment options, more than 30% of patients develop distant metastases, and the prognosis of these patients with metastases is extremely poor. Celastrol has been demonstrated to manifest multiple pharmacological activities, including induction of apoptosis in numerous types of cancer cell lines. Our previous studies have also suggested that Celastrol is capable of inducing apoptosis of human osteosarcoma cells via the mitochondrial-dependent pathway. The purpose of this study was to investigate the effects of Celastrol on the migration and invasion of human osteosarcoma U-2OS cells in vitro. Cell migration and invasion were investigated using wound healing and Boyden chamber Transwell assays. We observed that Celastrol suppressed cell invasion and migration in human osteosarcoma U-2OS cells. Furthermore, protein expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, inhibitor of κB kinase α/β, inhibitor of κB α, nuclear factor-κB (NF-κB subunit p65) and matrix metallo proteinase (MMP)-2 and -9 were measured by western blot analysis. We observed that the PI3K/Akt/NF-κB signaling pathway was inhibited following Celastrol treatment. In addition, the expression levels of MMP-2 and -9 proteins were also reduced significantly following Celastrol treatment. Therefore, we confirmed that Celastrol suppressed osteosarcoma U-2OS cell metastasis via downregulation of the PI3K/Akt/NF-κB signaling pathway in vitro.

Retracted: Knockdown of lncRNA HULC inhibits proliferation, migration, invasion, and promotes apoptosis by sponging miR‐122 in osteosarcoma

“…43 Besides, this pathway has been found to play a central role in the regulation of metastasis. 44 In addition to PI3K/AKT, JAK/STAT, and Notch pathways were also discovered as osteosarcoma signaling pathways and their specific role in osteosarcoma has been summarized in a recent review, 45 in which the activation of JAK/STAT and Notch pathways has been demonstrated to promote the development of osteosarcoma. Interestingly, complex interactions between the components of the PI3K/AKT pathway, and with components of JAK/STAT and Notch pathways, appear to be essential for facilitating and fuelling meningioma progression.…”

Effect of CXCR4 on Apoptosis in Osteosarcoma Cells via the PI3K/Akt/NF-κβ Signaling Pathway

“…Previous studies revealed that PI3K/AKT/NF-κβ signaling pathway played a vital role in regulating apoptosis in various cancer cells [41-44]. Yu et al indicated that celastrol induced apoptosis and decreased cell invasion and migration via inhibition of PI3K/AKT/NF-κβ signaling pathway in human osteosarcoma cells [45]. Thus, we further investigated the relationship between Akt and NF-κβ signaling followed CXCR4 down-regulation treatment in osteosarcoma cells.…”

Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines

“…47,48 Compound 2 (celastrol) has been reported to have activity against osteosarcoma, head and neck cancer, and glioblastoma. 49–51 Additionally, both compounds 1 and 2 have been reported to have activity against lung and prostate cancer cell lines through a variety of mechanisms. Compound 1 was reported to inhibit A549 and PC3 cell growth through glutathione depletion mechanisms, 52,53 while 2 inhibited A549 cells through activation of mitochondrial and Fas/FasL (Fas receptor/Fas ligand) apoptotic pathways and to have activity against DU145 prostate cancer cells via an hERG-dependent mechanism.…”