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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Breast cancer suppression by aplysin is associated with inhibition of PI3K/AKT/FOXO3a pathway
Xinling Zhang1, Tingting Zhuang2, Zhengyan Liang1
1The Institute of Human Nutrition, Medical College of Qingdao University, Qingdao 266021, China.
Abstract:
Aplysin, a bromosesquiterpene isolated from Aplysia kurodai, was explored as a potential anti-breast cancer agent by us. However, the mechanisms underlying the anticarcinogenic effect of aplysin remain unclear. Here, aplysin was found to remarkably suppress tumor growth in vivo, inhibit cell proliferation and promote apoptosis in vitro. Additionally, we demonstrated that aplysin attained these effects in part by down-regulating PI3K/AKT/FOXO3a signaling pathway. Aplysin treatment inhibited the phosphorylation levels of AKT (Ser-473) and AKT-dependent phosphorylation of FOXO3a (Ser-253) in breast cancer cell lines and breast cancer tissues. The expression levels of FOXO3a-targeted genes were also destabilized by aplysin, cyclin D1 and Bcl-XL were declined; however, p21CIP1, p27KIP1, Bim, TRAIL and FasL were increased both in vivo and in vitro. Furthermore, activation of the PI3K/AKT signaling pathway by an activator and silencing of FOXO3a by shRNA protected the cells from aplysin mediated growth suppression and apoptosis. In summary, our findings revealed that aplysin could suppress breast cancer progression by inhibiting PI3K/AKT/FOXO3a pathway, thereby suggesting a potential role of aplysin as a chemoprevention drug for patients with breast cancer.
Insights
Aplysin, a compound from Aplysia kurodai, inhibits breast cancer growth by down-regulating the PI3K/AKT/FOXO3a pathway, promoting apoptosis and suggesting its potential as a chemoprevention drug.
Area of Science:
- Marine Natural Products
- Cancer Biology
- Molecular Pharmacology
Background:
- Aplysin, a bromosesquiterpene from Aplysia kurodai, shows potential anti-cancer properties.
- The precise mechanisms of aplysin's anti-cancer effects, particularly against breast cancer, are not fully understood.
Purpose of the Study:
- To investigate the anti-breast cancer mechanisms of aplysin.
- To explore the role of the PI3K/AKT/FOXO3a signaling pathway in aplysin's effects.
Main Methods:
- In vivo tumor growth suppression assays.
- In vitro cell proliferation and apoptosis assays.
- Western blot analysis to assess protein phosphorylation and expression levels of key pathway and apoptosis-related genes.
- Gene silencing using shRNA and pathway activation using an activator.
Main Results:
- Aplysin significantly suppressed tumor growth in vivo and inhibited proliferation while promoting apoptosis in vitro.
- Aplysin down-regulated the PI3K/AKT/FOXO3a pathway by reducing phosphorylation of AKT and FOXO3a.
- Aplysin altered the expression of FOXO3a target genes, decreasing cyclin D1 and Bcl-XL, and increasing p21CIP1, p27KIP1, Bim, TRAIL, and FasL.
- Pharmacological activation of PI3K/AKT or silencing of FOXO3a conferred resistance to aplysin's anti-cancer effects.
Conclusions:
- Aplysin suppresses breast cancer progression by inhibiting the PI3K/AKT/FOXO3a signaling pathway.
- These findings highlight aplysin's potential as a chemopreventive agent for breast cancer.
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