| Cell Research: |
| Oncol Rep. 2014 Oct;32(4):1585-93. | | Isoalantolactone inhibits constitutive NF-κB activation and induces reactive oxygen species-mediated apoptosis in osteosarcoma U2OS cells through mitochondrial dysfunction.[Pubmed: 25109871] | Human osteosarcoma is an aggressive tumor which frequently resists chemotherapy; therefore, the search for new agents for its treatment is of great importance. Isoalantolactone, isolated from Inula spp., has been reported to inhibit the growth of several types of cancer cells. However, no prior research has been conducted to demonstrate the antiproliferative potential of Isoalantolactone on osteosarcoma. The present study is the first to investigate the effects of Isoalantolactone on cell viability in human osteosarcoma U2OS, MG-63 and Saos-2 cells, and its mechanism of action in Human osteosarcoma is an aggressive tumor which frequently resists chemotherapy; therefore, the search for new agents for its treatment is of great importance. Isoalantolactone, isolated from Inula spp., has been reported to inhibit the growth of several types of cancer cells. However, no prior research has been conducted to demonstrate the antiproliferative potential of Isoalantolactone on osteosarcoma.
The present study is the first to investigate the effects of Isoalantolactone on cell viability in human osteosarcoma U2OS, MG-63 and Saos-2 cells, and its mechanism of action in U2OS cells.
METHODS AND RESULTS:
Our results demonstrated that Isoalantolactone triggered S and mainly G2/M cell cycle phase arrest, accompanied by the downregulation of the expression of cyclin B1 at the protein and mRNA levels. Moreover, Isoalantolactone induced apoptosis that was associated with reactive oxygen species (ROS) generation and the dissipation of mitochondrial membrane potential (MMP). Furthermore, our results indicated that this compound upregulated DR5, FADD and cleaved caspase-8, increased the interation between DR5 and FADD, and inhibited the expression of nuclear NF-κBp65. We also found that Isoalantolactone-induced apoptosis was associated with the downregulation of Bcl-2 and upregulation of Bax, which finally led to the activation of caspase-3 and its downstream substrate, PARP, in osteosarcoma U2OS cells. Isoalantolactone-induced apoptosis was markedly abrogated when the cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, suggesting that the apoptosis-inducing effect of Isoalantolactone in osteosarcoma cells was mediated by reactive oxygen species.
CONCLUSIONS:
Taken together, our data demonstrated that Isoalantolactone induces ROS-dependent apoptosis in U2OS cells via a novel mechanism involving inhibition of NF-κBp65 and provide the rationale for further in vivo and preclinical investigation of Isoalantolactone against osteosarcoma. | | Arch Pharm Res. 2013 Oct;36(10):1262-9. | | Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways.[Pubmed: 23881702] | Isoalantolactone, a sesquiterpene lactone, possesses anti-fungal as well as cytotoxic properties. In this study, the effects of Isoalantolactone on cell viability, cell cycle, and apoptosis were investigated in human gastric adenocarcinoma SGC-7901 cells.
METHODS AND RESULTS:
The results demonstrated that Isoalantolactone induced morphological changes and decreased cell viability. Subsequently, we found that Isoalantolactone induced G2/M and S phase arrest, which was associated with a decrease in the expression level of cyclin B1. Apoptosis triggered by Isoalantolactone was visualized using propidium iodide (PI) and Annexin V-FITC/PI staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (ΔΨ m) that was due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3. Additionally, it was found that Isoalantolactone was involved in the inhibition of phosphorylation of PI3K/Akt.
CONCLUSIONS:
Isoalantolactone-induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase and PI3K/Akt dependent pathways, which gives the rationale for in vivo studies on the utilization of Isoalantolactone as a potential cancer therapeutic compound. |
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