Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo

Abstract

There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM) is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease.

Pristimerin inhibits the proliferation of HT1080 fibrosarcoma cells by inducing apoptosis

“…PM has been reported to have anti-tumor effects on human breast and lung cancer cells (21). We have previously shown that PM has an anti-tumor effect on human osteosarcomas (22). In the present study, PM exhibited a concentration-and time-dependent inhibition of cell viability in human fibrosarcoma cells.…”

“…Wu et al, reported that the IC50 values for human breast cancer cell lines, MCF-10A and MDA-MB-231, were 1.4-1.6 and 0.5-0.6 µM, respectively, after 24 h of PM administration and 1.0-1.2 and 0.4-0.6 µM, respectively, at 48 h. Wu et al, also reported that the IC50 values for human lung epithelial carcinoma cells, A549 and human liver cancer cell lines, HepG2 and Hep3B, were 0.4-0.6 µM at 72 h of PM administration (21). Mori et al, reported that the IC50 value for human osteosarcoma cell lines, MNNG and 143B, were 0.8-0.9 and 0.5-0.6 µM, respectively, at 24 h of PM administration, and 0.3-0.4 and 0.3-0.4 µM, respectively, at 48 h. Meanwhile, the IC50 values for human osteoblasts were reported to be ≥0.5 µM, at both 24 and 48 h of PM administration (22). In this study, The IC50 values for human fibrosarcoma cells were 0.16 µM at 24 h of PM administration, and 0.13 µM at 48 h of PM administration, whereas the IC50 values for human fibroblasts were 0.59 µM at 24 h of PM administration, and 0.32 µM at 48 h post PM administration.…”

“…In carcinomas and sarcomas, these pathways are closely associated with cell proliferation and anticancer drug resistance. PM has been shown to induce apoptosis in human osteosarcomas and carcinomas, such as colorectal cancer, ovarian cancer, and leukemia, via inhibition of AKT and MAPK signaling (15,22,25,26,34). Phosphorylation of AKT induces the downstream phosphorylation of NF-κB and mTOR, thereby activating them.…”

Systematic Understanding of the Mechanism of Pristimerin via Computational Target Fishing

“…the intrinsic (mitochondrial) pathway that activates caspases 9 and 3 via cytochrome C release from mitochondria, and the extrinsic (death receptor) pathway that activates caspases 8 and 10 through receptors (so-called "death receptor") present on the cell membrane surface [37]. In a recently study, Pristimerin induced elevation of caspase 3 and activation of upstream caspases 8 and 9 [38]. When Pristimerin induced apoptosis, it was in a dose-dependent manner.…”

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

“…The antiproliferative activity of pristimerin goes beyond colon-related cancers, it is extended to breast [346][347][348][349][350], melanomas [351], osteosarcoma [352], pancreatic [353,354], and prostate cancers [355][356][357][358]. Herein, we describe a few examples focusing on articles that have demonstrated potential mechanisms of action.…”