Erianin induces triple-negative breast cancer cells apoptosis by activating PI3K/Akt pathway

Abstract

Background: Triple-negative breast cancer (TNBC) is a refractory subtype of breast cancer, 25-30% of which have dysregulation in the PI3K/AKT pathway. This study investigated the anti-cancer effect of erianin on triple-negative breast cancer 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 anti-proliferation 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 nM and 78.58 nM, respectively. Erianin could cause cell cycle arrest at the G2/M phase, and the expressions of p21, p27 were upregulated, while the expressions of CDK1 and Cyclin B1 were downregulated. Erianin also induced apoptosis via the mitochondrial pathway, with the upregulation of the expression of Cyto C, PARP, Bax, activity form of Caspase-3, and Caspase-9. Furthermore, p-PI3K and p-Akt expression were downregulated 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.

Anticancer Activity of Erianin: Cancer-Specific Target Prediction Based on Network Pharmacology

“…Actually, erianin has been reported to be able to downregulate the phosphorylation of JAK2 and STAT3 in 2LL cells, and thus inhibit the expression of several inflammatory mediators, such as COX-2 (cyclooxygenase-2), HIF-1α, and IL-6 (interleukin-6) ( Su et al, 2017 ). Moreover, PIK3CA, as one of most important regulatory molecules involved in PI3K–AKT and MAPK signaling pathways, has been frequently identified as a target of erianin in various cancers ( Yang et al, 2020a ; Wang et al, 2021 ; Xu et al, 2021 ; Zhang et al, 2021a ). According to KEGG pathway analysis, KIT, ERBB2, FLT3, PIK3CA, and RET are enriched in central carbon metabolism in cancer, while ABL1, CHEK2, and CCND1 are highly related to the cell cycle process, both of which are relatively less explored.…”

The natural product erianin induces melanoma apoptosis through targeting the GSK3α-NF-κB pathway

“…Erianin could also cause irreparable DNA damage and deregulate mitotic regulators in hepatocellular carcinoma [7] . Moreover, erianin inhibited breast cancer, gastric cancer and oral squamous cell carcinoma through different mechanisms [6,19,22] . However, the roles of erianin in melanoma progression remain unclear.…”

Promoting Apoptosis, a Promising Way to Treat Breast Cancer With Natural Products: A Comprehensive Review

“…In 2019, Yeh et al (2019) reported that flavopereirine can induce apoptosis in MDA-MB-231cells by inhibiting the AKT/p38/ERK pathway. In 2021, Xu et al (2021) reported that erianin can induce TNBC cell apoptosis, which may be ascribed to the inhibition of the PI3K/AKT pathway. mTOR is one of the downstream members of the PI3K/AKT signaling pathway and is directly regulated by AKT.…”