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Sesamol induced apoptotic effect in lung adenocarcinoma cells through both intrinsic and extrinsic pathways
Boondaree Siriwarin1, Natthida Weerapreeyakul2
1Graduate School, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, 40002, Thailand.
Abstract:
Sesamol is a phenolic lignan found in sesame seeds (Sesamum indicum L.) and sesame oil. The anticancer effects and molecular mechanisms underlying its apoptosis-inducing effect were investigated in human lung adenocarcinoma (SK-LU-1) cells. Sesamol inhibited SK-LU-1 cell growth with an IC50 value of 2.7 mM and exhibited less toxicity toward normal Vero cells after 48 h of treatment (Selective index = 3). Apoptotic bodies-the hallmark of apoptosis-were observed in sesamol-treated SK-LU-1 cells, stained with DAPI. Sesamol increased the activity of caspase 8, 9, and 3/7, indicating that apoptotic cell death occurred through both extrinsic and intrinsic pathways. Sesamol caused the loss of mitochondrial transmembrane potential signifying intrinsic apoptosis induction. Decreasing Bid expression revealed crosstalk between the intrinsic and extrinsic apoptotic pathways; demonstrating clearly that sesamol induces apoptosis through both pathways in human lung adenocarcinoma (SK-LU-1) cells.
Insights
Sesamol, a compound from sesame seeds, effectively inhibits lung adenocarcinoma cell growth by inducing apoptosis through both extrinsic and intrinsic pathways, with minimal toxicity to normal cells.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- Sesamol is a natural phenolic lignan derived from sesame seeds (Sesamum indicum L.) and sesame oil.
- Lung adenocarcinoma is a significant subtype of non-small cell lung cancer.
- Understanding the molecular mechanisms of natural compounds for cancer therapy is crucial.
Purpose of the Study:
- To investigate the anticancer effects of sesamol on human lung adenocarcinoma (SK-LU-1) cells.
- To elucidate the molecular mechanisms by which sesamol induces apoptosis.
- To assess the selectivity of sesamol towards cancer cells compared to normal cells.
Main Methods:
- Cell viability assays were performed to determine the IC50 value of sesamol.
- DAPI staining was used to visualize apoptotic bodies.
- Caspase activity assays (caspase 8, 9, and 3/7) were conducted.
- Mitochondrial transmembrane potential was measured.
- Bid protein expression was analyzed.
Main Results:
- Sesamol inhibited SK-LU-1 cell growth with an IC50 of 2.7 mM.
- A selective index of 3 indicated lower toxicity to normal Vero cells.
- Apoptotic bodies were observed in sesamol-treated cells.
- Sesamol upregulated caspase activity and decreased mitochondrial potential, confirming apoptosis induction via extrinsic and intrinsic pathways.
- Decreased Bid expression demonstrated crosstalk between apoptotic pathways.
Conclusions:
- Sesamol exhibits significant anticancer effects against human lung adenocarcinoma cells.
- Apoptosis is the primary mechanism of sesamol-induced cell death.
- Sesamol triggers apoptosis through coordinated activation of both extrinsic and intrinsic pathways.
- Sesamol demonstrates potential as a therapeutic agent for lung adenocarcinoma due to its efficacy and selectivity.
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Apoptosis
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
