TRAIL and triptolide: an effective combination that induces apoptosis in pancreatic cancer cells
Daniel Borja-Cacho1, Yumi Yokoyama, Rohit K Chugh
1Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA.
Introduction:
An emerging therapy in oncology is the induction of apoptotic cell death through anti-death receptor therapy. However, pancreatic cancer is resistant to apoptosis including anti-death receptor therapy. We have previously described how triptolide decreases resistance to apoptosis in pancreatic cancer cells in vitro and in vivo. We hypothesized that triptolide decreases tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance in pancreatic cancer cells. The aim of this study was to evaluate the effects that combined therapy with TRAIL and triptolide have on different parameters of apoptosis.
Methods:
Four different pancreatic cancer cell lines were exposed to triptolide, TRAIL, or a combination of both drugs. We assessed the effects that combined therapy with TRAIL and triptolide has on cell viability, apoptosis, caspase-3 and caspase-9 activities, and poly(ADP)-ribose polymerase cleavage.
Results:
Pancreatic cancer cells were resistant to TRAIL therapy; however, combined therapy with triptolide and TRAIL significantly decreased the cell viability in all the cell lines and increased apoptotic cell death as a result of caspase-3 and caspase-9 activation.
Conclusions:
Pancreatic cancer is highly resistant to anti-death receptor therapy, but combined therapy with TRAIL and triptolide is an effective therapy that induces apoptotic cell death in pancreatic cancer cells.
Insights
Triptolide enhances anti-death receptor therapy by overcoming resistance in pancreatic cancer. Combined treatment with triptolide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively induces cancer cell death.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Pancreatic cancer exhibits resistance to apoptosis, a key mechanism targeted by emerging anti-death receptor therapies.
- Triptolide has demonstrated potential in reducing apoptosis resistance in pancreatic cancer cells.
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a critical component of anti-death receptor therapy.
Purpose of the Study:
- To investigate the efficacy of combining triptolide with TRAIL in overcoming pancreatic cancer's resistance to apoptosis.
- To evaluate the impact of this combination therapy on various apoptosis-related parameters.
Main Methods:
- Four pancreatic cancer cell lines were treated with triptolide, TRAIL, or a combination of both.
- Assessed were cell viability, apoptosis induction, caspase-3 and caspase-9 activation, and poly(ADP)-ribose polymerase cleavage.
Main Results:
- Pancreatic cancer cells showed resistance to TRAIL monotherapy.
- Combined triptolide and TRAIL therapy significantly reduced cell viability across all tested cell lines.
- The combination treatment markedly increased apoptotic cell death, evidenced by enhanced caspase-3 and caspase-9 activities.
Conclusions:
- Pancreatic cancer's inherent resistance to anti-death receptor therapy can be overcome.
- Combined therapy using triptolide and TRAIL represents a promising strategy for inducing apoptotic cell death in pancreatic cancer.
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