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Propofol induces ROS-mediated intrinsic apoptosis and migration in triple-negative breast cancer cells.

ABSTRACT: Propofol is widely applied in general anesthesia owing to its short effect and rapid recovery. Apart from its anesthetic advantages, propofol has also been observed to inhibit the growth of several types of cancer cells. Breast cancer is the most diagnosed cancer in females worldwide and triple negative breast cancer (TNBC) constitutes 15-20% of all breast cancer cases. TNBC is characterized by a high recurrence rate, which is associated with its high mortality rate. The present study aimed to evaluate apoptosis in MDA-MB-468 cells treated with propofol. The Cell Counting Kit-8 assay was used to assess proliferation in cells treated with different concentrations of propofol. In addition, Annexin V-FITC was used to detect apoptosis. Furthermore, the generation of reactive oxygen species (ROS) was examined. The relative expression of proteins in the intrinsic apoptosis pathway, such as Bak, Bax, Bcl-2, Cytochrome c, apoptotic peptidase-activating factor 1 (Apaf-1), Caspase 3 and Caspase 9, were calculated relative to GAPDH with western blot analysis. A wound healing assay was performed to examine the effect of propofol on MDA-MB-468 cell migration. The present study revealed that propofol inhibited the proliferation and increased the level of ROS in MDA-MB-468 cells. The expression levels of Cytochrome c, Apaf-1, Bax, Bak and cleaved Caspase 3/9 were upregulated compared with GAPDH. The level of Bcl-2 protein was upregulated by propofol at a concentration of 5 µM and downregulated at concentrations of 10 and 20 µM. In the wound-healing assay, propofol reduced the scratch distance and area. Taken together, the results of the present study suggested that propofol may induce ROS-mediated intrinsic apoptosis and promote migration in TNBC cells.

SUBMITTER: Wang H

PROVIDER: S-EPMC7285815 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Propofol induces ROS-mediated intrinsic apoptosis and migration in triple-negative breast cancer cells.

Wang Hao H Zhao Lidong L Wu Jing J Hong Jiang J Wang Songpo S

Oncology letters 20200513 1

Propofol is widely applied in general anesthesia owing to its short effect and rapid recovery. Apart from its anesthetic advantages, propofol has also been observed to inhibit the growth of several types of cancer cells. Breast cancer is the most diagnosed cancer in females worldwide and triple negative breast cancer (TNBC) constitutes 15-20% of all breast cancer cases. TNBC is characterized by a high recurrence rate, which is associated with its high mortality rate. The present study aimed to e ...[more]

PMID: 32566008

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Project description:Triple-negative breast cancer (TNBC) is an aggressive clinical subtype of breast cancer that is characterized by the lack of estrogen receptor (ER) and progesterone receptor (PR) expression as well as human epidermal growth factor receptor 2 (HER2) overexpression. The TNBC subtype constitutes approximately 10%-20% of all breast cancers, but has no effective molecular targeted therapies. Previous meta-analysis of gene expression profiles of 587 TNBC cases from 21 studies demonstrated high expression of Wnt signaling pathway-associated genes in basal-like 2 and mesenchymal subtypes of TNBC. In this study, we investigated the potential of Wnt pathway inhibitors in effective treatment of TNBC.Activation of Wnt pathway was assessed in four TNBC cell lines (BT-549, MDA-MB-231, HCC-1143 and HCC-1937), and the ER+ cell line MCF-7 using confocal microscopy and Western blot analysis of pathway components. Effectiveness of five different Wnt pathway inhibitors (iCRT-3, iCRT-5, iCRT-14, IWP-4 and XAV-939) on cell proliferation and apoptosis were tested in vitro. The inhibitory effects of iCRT-3 on canonical Wnt signaling in TNBC was evaluated by quantitative real-time RT-PCR analysis of Axin2 and dual-luciferase reporter assays. The effects of shRNA knockdown of SOX4 in combination with iCRT-3 and/or genistein treatments on cell proliferation, migration and invasion on BT-549 cells were also evaluated.Immunofluorescence staining of ?-catenin in TNBC cell lines showed both nuclear and cytoplasmic localization, indicating activation of Wnt pathway in TNBC cells. iCRT-3 was the most effective compound for inhibiting proliferation and antagonizing Wnt signaling in TNBC cells. In addition, treatment with iCRT-3 resulted in increased apoptosis in vitro. Knockdown of the Wnt pathway transcription factor, SOX4 in triple negative BT-549 cells resulted in decreased cell proliferation and migration, and combination treatment of iCRT-3 with SOX4 knockdown had a synergistic effect on inhibition of cell proliferation and induction of apoptosis.These data suggest that targeting SOX4 and/or the Wnt pathway could have therapeutic benefit for TNBC patients.

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Propofol induces ROS-mediated intrinsic apoptosis and migration in triple-negative breast cancer cells.

Publications

Propofol induces ROS-mediated intrinsic apoptosis and migration in triple-negative breast cancer cells.

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