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Published on: September 15, 2023
[Myrislignan Induces Apoptosis in Gastric Cancer Cell Line Through PI3K/AKT Signaling Pathway]
Yong-Jun Zhou1, Yong-Yue Pan2, Li-Jun Yang2
1Chengdu Lezhu Biotechnology Ltd., Chengdu 610041, China.
Objective:
To investigate the effect of myrislignan (MYR) on the apoptosis of gastric cancer cell line and its relationship with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.
Methods:
The gastric cells (SGC-7901) were treated with MYR at different concentrations, i.e., 0, 25, 50, 100, and 200 μmol/L, for 48 h and 72 h and the effect of MYR on the proliferation of SGC-7901 cells was measured by CCK-8 assay. Then, SGC-7901 cells were treated with different concentrations of MYR at 50, 100, and 200 μmol/L for 48 h. Meanwhile, a normal control group and a dimethyl sulfoxide (DMSO) solvent control group (0.1% DMSO) were established. Flow cytometry was used to determine the apoptosis rate of SGC-7901 cells. The protein expression levels of PI3K, AKT, Bcl-2-associated X protein (BAX), cysteine-dependent aspartate-specifc protease-3 (Caspase-3), and Caspase-9 were determined by Western blot. Then, PI3K activator (20 μmol/mL) was used to treat SGC-7901 cells for 48 h in 4 groups, the control group, 0.1% DMSO group, MYR group, and MYR+PI3K activator group, and the effect on MYR's induction of apoptosis and regulation of the protein expression levels of PI3K, AKT, BAX, Caspase-3, and Caspase-9 in SGC-7901 cells.
Results:
Compared with the control group, MYR at 50, 100 and 200 μmol/L inhibited the proliferation of gastric cancer cells, increased the apoptosis rate, down-regulated the protein expression levels of PI3K and AKT, and up-regulated the protein expression levels of BAX, Caspase-3, and Caspase-9 in a dose-dependent manner ( P<0.05). However, PI3K activator attenuated MYR-induced apoptosis in gastric cancer cells and MYR's regulation of PI3K, AKT, BAX, Caspase-3, and Caspase-9 protein expression ( P<0.05).
Conclusion:
MYR induces the expression of BAX, Caspase-3, and Caspase-9 proteins by inhibiting the PI3K/AKT signaling pathway, thereby promoting the apoptosis of gastric cancer cells.
Insights
Myrislignan (MYR) inhibits gastric cancer cell proliferation and promotes apoptosis by down-regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. This mechanism involves increasing BAX, Caspase-3, and Caspase-9 protein expression.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Gastric cancer remains a significant global health challenge.
- Identifying novel therapeutic agents targeting cancer cell apoptosis is crucial.
- The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway is frequently dysregulated in cancer.
Purpose:
- To investigate the anti-cancer effects of myrislignan (MYR) on gastric cancer cells.
- To elucidate the role of the PI3K/AKT signaling pathway in MYR-induced apoptosis.
- To determine the impact of MYR on key apoptosis-related proteins.
Summary:
- Myrislignan (MYR) significantly inhibited gastric cancer cell (SGC-7901) proliferation and induced apoptosis in a dose-dependent manner.
- MYR treatment led to the down-regulation of PI3K and AKT protein expression.
- Concurrently, MYR up-regulated the expression of pro-apoptotic proteins BAX, Caspase-3, and Caspase-9.
Impact:
- Myrislignan demonstrates potential as a therapeutic agent for gastric cancer.
- The findings highlight the PI3K/AKT pathway as a key target for MYR's anti-cancer activity.
- This research provides a molecular basis for the use of MYR in gastric cancer treatment.
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