Isobavachalcone induces cell death through multiple pathways in human breast cancer MCF-7 cells.
10.12122/j.issn.1673-4254.2022.06.11
- Author:
Yu Xin ZHANG
1
;
Mei Jia GAO
2
;
Mei Lin ZHU
2
;
Hong Mei LI
2
;
Tao MA
2
;
Cheng Zhu WU
2
Author Information
1. School of Laboratory Medicine, Bengbu Medical College, Bengbu 233030, China.
2. School of Pharmacy, Bengbu Medical College, Bengbu 233030, China.
- Publication Type:Journal Article
- Keywords:
apoptosis;
autophagy;
breast cancer cell;
isobavachalcone;
mitochondrial function
- MeSH:
Adenosine Triphosphate;
Cell Death;
Chalcones;
Humans;
MCF-7 Cells;
Neoplasms;
Proto-Oncogene Proteins c-akt;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
Reactive Oxygen Species/metabolism*;
bcl-2-Associated X Protein
- From:
Journal of Southern Medical University
2022;42(6):878-885
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the effects of isobavachalcone (IBC) on cell death of human breast cancer MCF-7 cells and explore the possible mechanism.
METHODS:MCF-7 cells were treated with different concentrations of IBC, and the changes in cell proliferation were assessed using MTT assay. Apoptosis of MCF-7 cells following treatment with 10, 20, and 40 μmol/L IBC was analyzed using flow cytometry with annexin V-FITC/PI double staining and fluorescence microscopy, and the expressions of apoptosis- and autophagy-related proteins (Bax, Bcl-2, Akt, p-Akt, p62, and LC3) were detected with Western blotting. Electron microscopy was used to observe the changes in submicrostructure of the cells following treatment with 40 μmol/L IBC. JC-1 assay kit, ATP assay kit, and reactive oxygen species (ROS) kit were used to determine the effect of IBC on mitochondrial function of the cells.
RESULTS:MTT assay showed that IBC significantly inhibited the proliferation of MCF-7 cells in a concentration- and time-dependent manner, with IC50 values of 38.46, 31.31, and 28.26 μmol/L at 24, 48, and 72 h, respectively. IBC also concentration-dependently induced apoptosis of MCF-7 cells. IBC-induced cell death was inhibited by z-VAD-fmk, a caspase inhibitor (P < 0.05), but not by the necroptosis inhibitor necrostatin-1 (Nec-1). Western blotting showed that IBC-induced MCF-7 cell apoptosis by increasing Bax expression and down-regulating the expressions of Bcl-2, Akt and p-Akt-473 (all P < 0.05). With the increase of IBC concentration, the expression of autophagy-related protein p62 and the LC3-II/I ratio increased progressively. Electron microscopy revealed the presence of autophagic bodies in IBC-treated MCF-7 cells. IBC treatment also resulted in decreased mitochondrial membrane potential and intracellular ATP level and increased ROS accumulation in MCF-7 cells (P < 0.05).
CONCLUSION:IBC is capable of inducing both apoptosis and autophagy in MCF-7 cells, suggesting the potential value of IBC as a lead compound in the development of anti-breast cancer agents.
