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Induction of apoptosis by dopamine in human oral tumor cell lines
H Terasaka1, A Tamura, F Takayama
1Department of Oral Diagnosis, Meikai University School of Dentistry, Saitama, Japan.
Abstract:
Dopamine dose-dependently reduced the viable cell number of both human salivary gland tumor HSG and oral squamous cell carcinoma HSC-2, HSC-4, and NA cells. CoCl2 significantly reduced both the cytotoxic activity and radical intensity of dopamine (determined by ESR spectroscopy). Dopamine produced DNA fragments (demonstrated by TUNEL method) and induced degradation of cytokeratin by activated caspase in HSG cells (detected by an immunocytochemical method, using a specific M30 monoclonal antibody). FACS analysis demonstrated that dopamine induced DNA fragmentation, a biochemical hallmark of apoptosis, in human promyelocytic leukemia HL-60 cells. The addition of catalase did not prevent the apoptosis-inducing activity of dopamine, reducing the possibility of the involvement of H2O2 for dopamine-induced apoptosis. Dopamine transiently induced p38 mitogen-activated protein kinase (MAP kinase) phosphorylation. However, an inhibitor of p38 MAP kinase phosphorylation, SB203680, failed to inhibit the dopamine-induced apoptosis. These data suggest that p38 phosphorylation at an early stage may not be a causative event for apoptosis.
Insights
Dopamine reduces cancer cell viability and triggers apoptosis in various human cancer cells. This study investigates dopamine
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Dopamine, a neurotransmitter, has shown potential anti-cancer properties.
- Understanding the mechanisms of dopamine's cytotoxic effects is crucial for therapeutic development.
Purpose of the Study:
- To investigate the cytotoxic effects of dopamine on human cancer cells.
- To elucidate the molecular mechanisms underlying dopamine-induced cell death, including apoptosis.
Main Methods:
- Cell viability assays on human salivary gland tumor (HSG) and oral squamous cell carcinoma (HSC-2, HSC-4, NA) cells.
- EPR spectroscopy to assess dopamine's radical intensity.
- TUNEL assay and immunocytochemistry (M30 antibody) to detect DNA fragmentation and caspase activation.
- Flow cytometry (FACS) analysis for apoptosis detection in HL-60 cells.
- Western blotting and kinase inhibitor studies to examine p38 MAP kinase involvement.
Main Results:
- Dopamine dose-dependently decreased viable cell numbers in HSG, HSC-2, HSC-4, and NA cells.
- Cobalt chloride (CoCl2) reduced dopamine's cytotoxic activity and radical intensity.
- Dopamine induced DNA fragmentation and activated caspase-mediated cytokeratin degradation in HSG cells.
- FACS analysis confirmed dopamine-induced apoptosis in HL-60 cells.
- Catalase did not inhibit dopamine-induced apoptosis, suggesting hydrogen peroxide (H2O2) is not involved.
- Dopamine transiently induced p38 MAP kinase phosphorylation, but a specific inhibitor (SB203680) did not block apoptosis.
Conclusions:
- Dopamine exhibits dose-dependent cytotoxic effects and induces apoptosis in multiple human cancer cell lines.
- The p38 MAP kinase pathway does not appear to be a primary mediator of dopamine-induced apoptosis.
- Further research is needed to fully understand the signaling pathways involved in dopamine's anti-cancer effects.