Vitamin E and other antioxidants inhibit human prostate cancer cells through apoptosis
K Gunawardena1, D K Murray, A W Meikle
1Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132, USA.
Background:
Many human prostate cancer cells have escaped the apoptotic effects of natural regulators of cell growth such as transforming growth factor betal (TGF beta-1) and tumor necrosis factor (TNF).
Methods:
Prostate cancer cell growth was investigated by treating with antioxidants. DU-145 (androgen-unresponsive), LNCaP (androgen-responsive), and ALVA-101 (androgen moderately responsive) were grown in RPMI-1640 medium supplemented with bovine fetal calf serum and antibiotics, and were treated with various antioxidants for 1-7 days. Cell growth was then determined with the Cell Titer 96 AQ assay, and apoptosis was assessed by cell death detection ELISA, nuclear morphology, and TUNEL techniques.
Results:
Cells treated with or without (+/-)-alpha-tocopherol (vitamin E) for 1-7 days at concentrations from 0.078-2.5 microg/ml modestly affected cell growth compared to other antioxidants tested. Tocopherol produced a significant (P < 0.01) inhibition of ALVA-101 and LNCaP (10-24% of control; 0.078-2.5 microg/ml; at 6 days; n = 6). DU-145 cells were not growth-inhibited significantly. However, pyrrolidinedithiocarbamate (PDTC) produced a significant (P < 0.01, n = 6; 17-80% of control; 2.5-20 microg/ml; 1-7 days) inhibition of DU-145 and ALVA-101 cells. A significant (P < 0.01) and maximum inhibition of LNCaP cells occurred at all concentration of PDTC (2. 5-20 microg/ml). A third compound, diethyldithiocarbamic acid (DETC), incubated for 1-7 days, produced a significant dose response suppression of cell growth of DU-145 and ALVA-101 cells (P < 0.01; 14-88% of control; 1.25-80 microg/ml; n = 6). LNCaP cells were inhibited by DETC (P < 0.01; 28% of control; 1.25-80 microg/ml; n = 6). All three antioxidants tested stimulated apoptosis in actively dividing ALVA-101, DU-145, and LNCaP cells (P < 0.01; n = 6), but confluent cells were affected less. Testosterone had additive inhibitory effects when combined with PDTC in ALVA-101 cells; however, the other cell lines were not influenced.
Conclusions:
These results demonstrate that antioxidants modulate human prostate cancer cell proliferation by altering apoptosis in dividing cells, and this necrosis or apoptosis in confluent cells is not as effective.
Insights
Antioxidants like vitamin E, PDTC, and DETC inhibit prostate cancer cell growth by promoting apoptosis in dividing cells. Confluent cells showed less response to these antioxidant treatments.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Prostate cancer cells often evade natural apoptosis regulators like TGF-β1 and TNF.
- Understanding resistance mechanisms is crucial for developing new therapies.
Purpose of the Study:
- To investigate the effects of antioxidants on human prostate cancer cell proliferation and apoptosis.
- To compare the efficacy of different antioxidants across various prostate cancer cell lines.
Main Methods:
- Three human prostate cancer cell lines (DU-145, LNCaP, ALVA-101) were treated with antioxidants (+/-)-alpha-tocopherol, PDTC, and DETC.
- Cell growth was assessed using the Cell Titer 96 AQ assay.
- Apoptosis was evaluated through ELISA, nuclear morphology, and TUNEL assays.
Main Results:
- (+/-)-alpha-tocopherol showed modest growth inhibition in ALVA-101 and LNCaP cells.
- PDTC and DETC significantly inhibited growth in DU-145, ALVA-101, and LNCaP cells.
- All tested antioxidants stimulated apoptosis in actively dividing cells but had less effect on confluent cells.
Conclusions:
- Antioxidants modulate prostate cancer cell proliferation by inducing apoptosis in dividing cells.
- The effectiveness of antioxidant-induced apoptosis is dependent on cell proliferation status.
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