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Diallyl trisulfide induces osteosarcoma cell apoptosis through reactive oxygen species-mediated downregulation of the
Hongliang Wang1, Na Sun2, Xin Li1
1Department of Orthopedics, Qilu Hospital, Shandong University, Ji'nan, Shandong 250012, P.R. China.
Abstract:
Diallyl trisulfide (DATS) is a natural organosulfur compound isolated from garlic, and has been reported to possess anticancer activities. However, the cancer growth inhibitory effects and molecular mechanisms in human osteosarcoma cells have not been well studied. The present study demonstrated that DATS significantly reduced cell viability in a dose- and time-dependent manner in MG63 and MNNG/HOS cells. DATS-induced G0/G1 phase arrest was found to correlate with a decrease in cyclin D1 in concomitance with an increase in p21 and p27. DATS induced a marked increase in reactive oxygen species (ROS) levels and collapse of mitochondrial membrane potential (Δψm) in the osteosarcoma cells. DATS induced apoptosis in the MG63 and MNNG/HOS cells via inhibition of the PI3K/Akt signaling pathway and through the mitochondrial apoptotic pathway. The efficiency of DATS basically approached the efficacy of LY294002, a specific PI3K inhibitor. However, N-acetylcysteine (NAC), a general ROS scavenger, completely blocked the DATS-induced ROS increase, inhibition of the PI3K/Akt pathway and cell apoptosis. Overall, DATS has the potential to be developed as a new anticancer drug. The mechanisms of action involve the ROS-mediated downregulation of the PI3K/Akt pathway.
Insights
Diallyl trisulfide (DATS), a garlic compound, effectively inhibits osteosarcoma cell growth by inducing apoptosis. Its anticancer effects are mediated by reactive oxygen species (ROS) and the PI3K/Akt pathway.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Diallyl trisulfide (DATS) is a natural organosulfur compound found in garlic with reported anticancer properties.
- The specific mechanisms of DATS in human osteosarcoma cells remain underexplored.
Purpose of the Study:
- To investigate the anticancer effects of DATS on human osteosarcoma cells.
- To elucidate the molecular mechanisms underlying DATS-induced cell death.
Main Methods:
- Cell viability assays in MG63 and MNNG/HOS osteosarcoma cell lines.
- Flow cytometry to assess cell cycle phase distribution and mitochondrial membrane potential.
- Measurement of reactive oxygen species (ROS) levels.
- Western blotting to analyze key proteins in cell signaling pathways.
- Inhibition studies using N-acetylcysteine (NAC) and LY294002.
Main Results:
- DATS significantly reduced osteosarcoma cell viability in a dose- and time-dependent manner.
- DATS induced G0/G1 cell cycle arrest, increased ROS production, and decreased mitochondrial membrane potential.
- Apoptosis was induced via inhibition of the PI3K/Akt pathway, and this was found to be ROS-dependent.
- N-acetylcysteine (NAC) treatment blocked DATS-induced ROS, PI3K/Akt inhibition, and apoptosis.
Conclusions:
- DATS exhibits potent anticancer activity against human osteosarcoma cells.
- The mechanism involves ROS-mediated downregulation of the PI3K/Akt pathway, leading to apoptosis.
- DATS shows potential as a novel therapeutic agent for osteosarcoma.
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