Daphnoretin Arrests the Cell Cycle and Induces Apoptosis in Human Breast Cancer Cells
Qi Xie1, Xinmei Fan2, Yonghong Han3
1Jiangsu College of Nursing, 9 Science and Technology Avenue, Huaian, 223005, Jiangsu China.
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.
Insights
Daphnoretin, from Daphne giraldii, inhibits breast cancer cell growth by halting the cell cycle and triggering apoptosis. This natural compound impacts key proteins and the PI3K/AKT pathway, offering potential therapeutic strategies.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Daphnoretin, a compound from Daphne giraldii, exhibits antitumor properties in various cancer types.
- The specific mechanisms of daphnoretin's action in breast cancer remain largely uninvestigated.
Purpose of the Study:
- To explore the antitumor effects of daphnoretin on human breast cancer cells.
- To elucidate the molecular mechanisms underlying daphnoretin's anti-breast cancer activity.
Main Methods:
- Cell proliferation assays using MCF-7 and MDA-MB-231 breast cancer cell lines.
- Cell cycle analysis and apoptosis assays (Western blotting for apoptosis-related proteins and cell cycle regulators).
- Investigation of the phosphoinositide 3-kinase/AKT (PI3K/AKT) signaling pathway.
Main Results:
- Daphnoretin significantly suppressed the proliferation of MCF-7 and MDA-MB-231 cells.
- Daphnoretin induced S-phase cell cycle arrest by modulating p21, cyclin E, and CDK2 levels.
- Daphnoretin promoted apoptosis by altering BCL-2, BAX, and caspase levels, and inhibited the PI3K/AKT pathway.
Conclusions:
- Daphnoretin exhibits significant anti-breast cancer effects by inducing cell cycle arrest and apoptosis.
- The PI3K/AKT pathway is involved in the mechanism of daphnoretin's anti-cancer activity in breast cancer cells.
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