Triptolide induces the cell apoptosis of osteosarcoma cells through the TRAIL pathway

Abstract

Research on triptolide, a diterpenoid epoxide found in the Thunder God Vine Tripterygium wilfordii, has increased our knowledge of the pharmacology, pharmacokinetics, toxicology and clinical application of this agent. In the present study, we aimed to identify the effects of triptolide on the apoptosis of osteosarcoma cells and to evaluate the anti-proliferative action of this agent. MG-63 cells were treated either with various doses of triptolide (50, 100 or 200 nM) or DMSO for 6, 12 and 24 h. Treatment with triptolide effectively suppressed the cell viability and induced the apoptosis of osteosarcoma MG-63 cells as detected by MTT assay and flow cytometry, respectively. In addition, by using caspase-3, caspase-8 and caspase-9 activity assays and western blot analysis, the anticancer effects of triptolide against osteosarcoma growth were found to involve activation of the DR-5/p53/Bax/caspase-9/ caspase-3 signaling pathway and the DR-5/FADD/caspase-8/lysosomal/cathepsin B/caspase-3 signaling pathway in the MG-63 cells. An important factor in the anticancer effects of triptolide against osteosarcoma was TRAIL-DR-5. The data suggest that triptolide may be a potential novel chemotherapeutic agent for osteosarcoma and acts through the TRAIL-DR-5 signaling pathway.

Triptolide inhibits vascular endothelial growth factor‑mediated angiogenesis in human breast cancer cells

“…The results of western blot analysis in the present study indicate that triptolide suppresses ERK1/2 activation and inhibits HIF1-α expression in breast cancer cells. Triptolide has been demonstrated to regulate several key signaling pathways in tumor progression, including the phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt/Serine/threonine-protein kinase mTOR, tumor necrosis factor (TNF)-related apoptosis-inducing ligand and nuclear factor (NF)-κB signaling pathways ( 26 , 27 ). The present study examined Akt phosphorylation following triptolide treatment and identified a slight decrease in p-Akt, although this decrease was not significant.…”

The analgesic effects of triptolide in the bone cancer pain rats via inhibiting the upregulation of HDACs in spinal glial cells

“…Triptolide (T10) is a major active ingredient extracted from the Chinese herb, Tripterygium wilfordii hook F (TWHF) [ 5 ]. It has been shown that T10 can effectively inhibit many kinds of cancers [ 6 ], including osteosarcoma [ 7 , 8 ], pancreatic cancer [ 9 , 10 ], breast cancer [ 11 , 12 ], and leukemia [ 13 , 14 ]. Recent studies have demonstrated T10 to be effective in ameliorating some non-cancer pain status, such as neuropathic pain [ 5 , 15 , 16 ].…”

The Role of Cathepsins in the Growth of Primary and Secondary Neoplasia in the Bone

“…CatB activity is significantly increased following 1-2 h of exposure to TRAIL [149]. Triptolide inhibits cell viability and proliferation, and induced apoptosis in OS cell line MG-63 [148]. Previous studies by Owa et al, support this finding, citing that triptolide induces lysosomal-mediated programmed cell death in MCF-7 BCa cells through CatB and caspase-3 [152].…”

“…Intriguingly, CatB has been discovered to also demonstrate anticancer effects in the OS cell line MG-63, which is mediated through the activation of the DR-5/p53/Bax/caspase-9/-3 signaling pathway and the DR-5/FADD/caspase-8/lysosomal/cathepsin B/caspase-3 signaling pathway [148]. The release of CatB from the lysosome into the cytosol induces cell death in vitro [44].…”

“…It is believed that the upregulation of CatB increases caspase 3 cleavage and induced apoptosis. During the early stages of apoptosis, cytosolic levels of CatB are increased [148]. Triptolide increases lysosomal membrane permeability, causing a leakage of CatB into the cytosol within the first 3 h of treatment, triggering the apoptotic cascade.…”