Apoptotic pathway induced by diallyl trisulfide in pancreatic cancer cells
Hong-Bing Ma1, Shan Huang1, Xiao-Ran Yin1
1Hong-Bing Ma, Shan Huang, Xiao-Ran Yin, Yang Zhang, Department of Radiotherapy of Tumor Hospital, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
Aim:
To investigate the effects of diallyl trisulfide (DATS), a garlic-derived organosulfur compound, in pancreatic cancer cells.
Methods:
Human pancreatic cancer cells with wild-type p53 gene (Capan-2) and normal pancreatic epithelial cells (H6C7) were cultured in RPMI1640. DATS was prepared at a concentration of 100 μmol/L. Cell viability was determined via the methyl thiazolyl tetrazolium assay. Apoptotic cells were detected by TUNEL assay. Cell cycle analysis was performed using flow cytometry. Protein expression was determined by Western blot. Bax and Bcl-2 expression was detected by immunofluorescence. Apoptosis genes and cell cycle were assessed by quantitative real-time polymerase chain reaction.
Results:
DATS suppressed the viability of cultured human pancreatic cancer cells (Capan-2) by increasing the proportion of cells in the G2/M phase and induced apoptotic cell death. Western blot analysis indicated that DATS enhanced the expression of Fas, p21, p53 and cyclin B1, but downregulated the expression of Akt, cyclin D1, MDM2 and Bcl-2. DATS induced cell cycle inhibition which was correlated with elevated levels of cyclin B1 and p21, and reduced levels of cyclin D1 in Capan-2 cells and H6C7 cells. DATS-induced apoptosis was markedly elevated in Capan-2 cells compared with H6C7 cells, and this was correlated with elevated levels of cyclin B1 and p53, and reduced levels of Bcl-2. DATS-induced apoptosis was correlated with down-regulation of Bcl-2, Akt and cyclin D1 protein levels, and up-regulation of Bax, Fas, p53 and cyclin B protein levels in Capan-2 cells.
Conclusion:
DATS induces apoptosis of pancreatic cancer cells (Capan-2) and non-tumorigenic pancreatic ductal epithelial cells (H6C7).
Insights
Diallyl trisulfide (DATS), a compound from garlic, effectively suppresses pancreatic cancer cell viability and triggers apoptosis. This study reveals DATS
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Pancreatic cancer remains a significant health challenge with limited effective treatments.
- Organosulfur compounds, like diallyl trisulfide (DATS) found in garlic, show potential anti-cancer properties.
- Understanding DATS' mechanisms in pancreatic cancer is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the anti-cancer effects of diallyl trisulfide (DATS) on human pancreatic cancer cells.
- To elucidate the molecular mechanisms underlying DATS-induced apoptosis and cell cycle arrest in pancreatic cancer.
- To compare the effects of DATS on cancer cells versus normal pancreatic epithelial cells.
Main Methods:
- Human pancreatic cancer cells (Capan-2) and normal pancreatic epithelial cells (H6C7) were cultured.
- Cell viability was assessed using the methyl thiazolyl tetrazolium assay.
- Apoptosis, cell cycle, and protein expression (Western blot, immunofluorescence, qPCR) were analyzed.
Main Results:
- DATS significantly suppressed pancreatic cancer cell viability and induced apoptosis, particularly in Capan-2 cells.
- DATS caused cell cycle arrest at the G2/M phase, correlating with altered cyclin B1, p21, and cyclin D1 levels.
- DATS modulated key apoptosis-related proteins, including upregulation of Fas, p53, and Bax, and downregulation of Bcl-2 and Akt.
Conclusions:
- Diallyl trisulfide (DATS) demonstrates potent apoptosis-inducing effects on pancreatic cancer cells.
- DATS affects both cancer and normal pancreatic cells, with a more pronounced apoptotic effect on cancer cells.
- DATS-mediated cell cycle inhibition and apoptosis involve the modulation of critical cell cycle and apoptosis regulatory proteins.
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