Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway
Yonggang Xu1, Rong Fang2, Jie Shao1
1Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
Background:
Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25-30% of which have dysregulation in the PI3K/AKT pathway. The present study investigated the anticancer effect of erianin on TNBC cell line and its underlying mechanism.
Methods:
After treatment with erianin, MTT assay was employed to determine the MDA-MB-231 and EFM-192A cell proliferation, the nucleus morphological changes were observed by DAPI staining. The cell cycle and apoptotic proportion were detected by flow cytometry. Western blot was performed to determine the cell cycle and apoptosis-related protein expression and PI3K pathways. Finally, the antiproliferative activity of erianin was further confirmed by adding or not adding PI3K agonists SC79.
Results:
Erianin inhibited the proliferation of MDA-MB-231 and EFM-192A cells in a dose-dependent manner, the IC50 were 70.96 and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G2/M phase, and the expressions of p21 and p27 were up-regulated, while the expressions of CDK1 and Cyclin B1 were down-regulated. Erianin also induced apoptosis via the mitochondrial pathway, with the up-regulation of the expression of Cyto C, PARP, Bax, active form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were down-regulated by erianin. After co-incubation with SC79, the cell inhibition rate of erianin was decreased, which further confirmed that the attenuated PI3K/Akt pathway was relevant to the pro-apoptotic effect of erianin.
Conclusions:
Erianin can inhibit the proliferation of TNBC cells and induce cell cycle arrest and apoptosis, which may ascribe to the abolish the activation of the PI3K/Akt pathway.
Insights
Erianin effectively inhibits triple-negative breast cancer (TNBC) cell proliferation by inducing cell cycle arrest and apoptosis. This anticancer effect is linked to the downregulation of the PI3K/Akt pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype with frequent PI3K/AKT pathway dysregulation.
- Erianin is investigated for its potential anticancer effects on TNBC.
Purpose of the Study:
- To investigate the anticancer effects of erianin on TNBC cells.
- To elucidate the underlying molecular mechanisms, including PI3K/AKT pathway involvement.
Main Methods:
- MTT assays and DAPI staining assessed proliferation and nuclear morphology.
- Flow cytometry analyzed cell cycle and apoptosis.
- Western blotting detected key proteins in cell cycle, apoptosis, and PI3K/AKT pathways.
- PI3K agonist SC79 was used to confirm pathway involvement.
Main Results:
- Erianin inhibited TNBC cell proliferation (IC50: 70.96-78.58 nM).
- Erianin induced G2/M cell cycle arrest and apoptosis via the mitochondrial pathway.
- Erianin downregulated p-PI3K and p-Akt, with effects reversed by SC79.
Conclusions:
- Erianin exhibits significant antiproliferative and pro-apoptotic effects on TNBC cells.
- The observed effects are mediated by the inhibition of the PI3K/Akt pathway.
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