Propofol induces proliferation partially via downregulation of p53 protein and promotes migration via activation of the Nrf2 pathway in human breast cancer cell line MDA-MB-231.

Abstract

Antioxidants induce the proliferation of cancers by decreasing the expression of p53. Propofol, one of the most extensively used intravenous anesthetics, provides its antioxidative activity via activation of the nuclear factor E2-related factor-2 (Nrf2) pathway, but the mechanisms involved in the effects remain unknown. Thus, we aimed to investigate the function of p53 and Nrf2 in the human breast cancer cell line MDA-MB-231 following treatment with propofol. The cells were treated with propofol (2, 5 and 10 µg/ml) for 1, 4 and 12 h, and MTT assay was used to evaluate cell proliferation, and a wound healing assay was used to evaluate cell migration. Cell apoptosis, caspase-3 activity, and western blot analysis for p53 and Nrf2 protein were also assessed. Finally, PIK-75, a potent Nrf2 inhibitor, was used to confirm the effects of Nrf2 after treatment with propofol. Treatment of MDA-MB‑231 cells with propofol resulted in increased proliferation and migration in a dose- and time-dependent manner. After treatment with propofol for 12 h, the Nrf2 protein expression was increased, while the percentage of apoptotic cells, caspase-3 activity, and expression of p53 were significantly decreased. Additionally, treatment with the Nrf2 inhibitor increased the percentage of apoptotic cells, inhibited the migration almost completely, and decreased the degree of proliferation, while the expression of p53 was not affected. In conclusion, propofol increased the proliferation of human breast cancer MDA-MB‑231 cells, which was at least partially associated with the inhibition of the expression of p53, and induced cell migration, which was involved in the activation of the Nrf2 pathway.

• Authors: Chao Meng, Linlin Song, Juan Wang, Di Li, Yanhong Liu, Xiaoguang Cui
• Journal: Oncology reports (Oncol Rep) Vol. 37 Issue 2 Pg. 841-848 (Feb 2017) ISSN: 1791-2431 [Electronic] Greece
• PMID: 28035403 (Publication Type: Journal Article)

Chemical References

• Hypnotics and Sedatives
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• TP53 protein, human
• Tumor Suppressor Protein p53
• Propofol

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hypnotics and Sedatives (pharmacology)
• NF-E2-Related Factor 2 (metabolism)
• Propofol (pharmacology)
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (antagonists & inhibitors, metabolism)
• Wound Healing (drug effects)