Gambogic acid inhibits epithelial–mesenchymal transition in breast cancer cells through upregulation of SIRT1 expression in vitro. Issue 1 (5th April 2022)

• Record Type: Journal Article
• Authors: Jiang, Shi‐ye; Yu, Jun; Zhu, Ming; Zhang, Xiao‐mei; Zhang, Yuan‐ying; Zhang, Qin; Hu, Qing; Lv, Min
• Is Part Of: Precision medical sciences. Volume 11:Issue 1(2022)
• Page Start: 14
• Page End: 22
• Publication Date: 2022-04-05
• Subjects: breast cancer -- epithelial–mesenchymal transition (EMT) -- gambogic acid -- SIRT1; Personalized medicine -- Periodicals; Cancer -- Treatment -- Periodicals; Oncology -- Periodicals; 616.994
• DOI: 10.1002/prm2.12057
• Languages: English
• ISSNs: 2642-2514

Abstract

Abstract: Gambogic acid (GA) is a natural product that selectively induces apoptosis of cancer cells in vitro with high efficiency and low toxicity. Our previous data have shown inhibitory effects of GA on breast cancer cells. However, the detailed mechanisms for GA remain largely unknown. This study aimed to investigate the effect of GA on TGF‐β1‐induced tumor invasion and EMT in MDA‐MB‐231 cells, and contribution of elevated SIRT1 to antitumor effects of GA. Human breast cell MDA‐MB‐231 and MDA‐MB‐231 were incubated with TGF‐β1 (100 ng/ml) and GA. Cell viability was determined by MTT assay, while tumor invasion was determined by Boyden chamber invasion assay. The mRNA levels of SIRT1 and TGF‐β1 were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR). The protein expressions of SIRT1 and EMT‐associated mesenchymal marker Vimentin were measured by Western blotting. Interleukin‐6 (IL‐6) protein content was measured by enzyme linked immunosorbent assays (ELISAs). Our results showed that, GA showed decreased proliferation in MDA‐MB‐231 cells, especially in MDA‐MB‐231 cells with TGF‐β1 incubation. GA inhibited tumor invasion and EMT in TGF‐β1‐treated MDA‐MB‐231 cells. GA increased mRNA and protein expression of SIRT1 in MDA‐MB‐231 cells with and without TGF‐β1 treatment. SIRT1 mRNA level in MDA‐MB‐231 cells was increased by TGF‐β1 incubation and decreased by GA treatment. In addition, the production of IL‐6 was increased by TGF‐β1, and decreased by GA. In conclusion, GA inhibits tumor invasion and EMT in breast cancer, potentially through upregulating SIRT1 expression. This study provides a novel antitumor effect of GA in breast cancer. Abstract : GA upregulated mRNA and protein expressions of SIRT1 in TGF‐β1‐breast cancer cells, we have demonstrated that the SIRT1 participates in anticancer effects on progressive phase of breast cancer.