Daphnoretin Arrests the Cell Cycle and Induces Apoptosis in Human Breast Cancer Cells

Abstract

Emerging evidence has shown that daphnoretin, one of the main active ingredients of Daphne giraldii Nitsche, processes antitumor activities in several tumor cells (e.g., colon cancer, lung cancer, cervical cancer, and osteosarcoma). However, the antitumor effect and its mechanism in breast cancer are unexplored. In this study, our data indicated that daphnoretin obviously suppressed the proliferation of breast cancer MCF-7 and MDA-MB-231 cells. Further studies showed that daphnoretin remarkably increased the p21 level, decreased cyclin E and CDK2 levels, and then arrested the cell cycle at the S phase. Moreover, daphnoretin obviously lowered the BCL-2 level and raised the levels of BAX and cleaved caspase-9 and -3, leading to cell apoptosis. Furthermore, daphnoretin remarkably decreased the ratio of p-PI3K/PI3K and p-AKT/AKT in breast cancer cells. Collectively, these findings demonstrated that daphnoretin could suppress breast cancer cell proliferation through cell cycle arrest and inducing apoptosis, which is related to the PI3K/AKT pathway.

Identification of an Alepterolic Acid Derivative as a Potent Anti‐Breast‐Cancer Agent via Inhibition of the Akt/p70S6K Signaling Pathway

“…It is well documented that activation of Akt induced by the survival factors can suppress apoptosis by phosphorylation [46] . Accumulating evidence suggests that cell proliferation, survival, invasion, migration, apoptosis, glucose metabolism and DNA repair are closely related to the aberrant activation of the phosphatidylinositol 3‐kinase (PI3 K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling [47] . Akt is the key regulator in this pathway, activated Akt can phosphorylate the proapoptotic proteins in the Bcl‐2 family to inhibit their function.…”

HER2 low expression breast cancer subtyping and their correlation with prognosis and immune landscape based on the histone modification related genes

“…In BRCA 4T1 cells, the cells were arrested in the S phase because of the percentage of cells in S phase increased and cells in G1/G0 phase decreased after treating with resveratrol 33 . Daphnoretin could remarkably increase the p21 level and decrease cyclin E and CDK2 levels, and then arrest the cell cycle at the S phase in BRCA 34 . The CDCD20 down-regulation combined with radiation could restrain proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of hepatoma cells with p53 mutated Hep3B decreased with increasing irradiation dose 35 .…”

The crosstalk between microbiota and metabolites in AP mice: an analysis based on metagenomics and untargeted metabolomics

“…Interestingly, the inactivation of Pta-ackA signaling significantly increased the rate of glucose consumption, inhibited bacterial growth, and resulted in the death of Staphylococcus aureus , suggesting that the Pta-ackA pathway is critical to bacterial survival ( Sadykov et al., 2013 ). Several studies have shown that daphnoretin (coumarins and derivatives) has significant anti-inflammatory and antitumor effects ( Gu and He, 2012 ; Yu et al., 2019 ; Xie et al., 2022 ). Daphnoretin can suppress IL-1β-induced chondrocyte apoptosis by inhibiting endoplasmic reticulum stress and NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and suppressing osteoarthritis ( Zhou and Wang, 2022 ).…”

“…Several studies have shown that daphnoretin (coumarins and derivatives) has significant anti-inflammatory and antitumor effects (Gu and He, 2012;Yu et al, 2019;Xie et al, 2022). Daphnoretin can suppress IL-1b-induced chondrocyte apoptosis by inhibiting endoplasmic reticulum stress and NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) inflammasome activation and suppressing osteoarthritis (Zhou and Wang, 2022).…”