Effect of the mycotoxin deoxynivalenol in combinational therapy with TRAIL on prostate cancer cells
Dominika Ewa Habrowska-Górczyńska1, Karolina Kowalska1, Kinga Anna Urbanek1
1Department of Cell Cultures and Genomic Analysis, Medical University of Lodz, Zeligowskiego 7/9, Lodz 90-752, Poland.
Abstract:
Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is reported as a promising anti-cancer therapeutic target. Unfortunately, prostate cancer cells (PCa) are partially resistant to TRAIL-induced apoptosis limiting its therapeutic potential. The existing body of knowledge suggests that naturally produced compounds, such as mycotoxin deoxynivalenol (DON), might potentially sensitize cells to TRAIL treatment and improve the efficiency of therapy. Previously, we observed that DON induces oxidative stress and apoptosis in PCa cell lines. Thus we addressed here whether DON can sensitize PCa cells to TRAIL-induced apoptosis. Our data demonstrates that three out of four tested PCa cell lines pretreated with DON increased TRAIL-induced apoptosis detected with flow cytometry. This effect was associated with oxidative stress (LNCaP and DU-145 cell line) and elevated DNA damage (DU-145, LNCaP, and 22Rv1 cell lines). Next, in the animal model we inoculated PC tumor to SCKID mice followed by administration of DON intraperitoneally and/or TRIAL intravenously. During 21 days monitoring of tumor growth, the animals received 7 doses of DON, TRAIL, DON+TRAIL or control injections. No significant reduction in tumor mass was observed after combinational treatment of TRAIL and DON compared to 1 μg/kg of body weight DON treatment alone, which itself decreased the tumor growth. However, despite the lack of the TRAIL + DON effect, DON itself inducing apoptosis is an interesting compound worth investigating in the context of other combination therapies.
Insights
Deoxynivalenol (DON) may sensitize prostate cancer cells to TRAIL-induced apoptosis, but combination therapy showed no significant tumor reduction in mice. DON alone decreased tumor growth, warranting further investigation.
Area of Science:
- Oncology
- Molecular Biology
- Toxicology
Background:
- Prostate cancer (PCa) exhibits partial resistance to Tumor Necrosis Factor-Related Apoptosis-Induced Ligand (TRAIL)-induced apoptosis, limiting its therapeutic efficacy.
- Naturally occurring compounds, like the mycotoxin deoxynivalenol (DON), are being explored for their potential to sensitize cancer cells to apoptosis.
- Previous studies indicated DON induces oxidative stress and apoptosis in PCa cell lines.
Purpose of the Study:
- To investigate whether deoxynivalenol (DON) can sensitize prostate cancer (PCa) cells to TRAIL-induced apoptosis.
- To evaluate the combined effect of DON and TRAIL on PCa tumor growth in an in vivo animal model.
Main Methods:
- In vitro: Pretreatment of four PCa cell lines with DON followed by TRAIL, assessing apoptosis via flow cytometry.
- In vitro: Measurement of oxidative stress and DNA damage markers.
- In vivo: Xenograft model in SCID mice, administering DON and/or TRAIL, monitoring tumor growth over 21 days.
Main Results:
- DON pretreatment enhanced TRAIL-induced apoptosis in three out of four PCa cell lines.
- This sensitization was linked to increased oxidative stress and DNA damage in specific cell lines.
- In vivo, DON alone (1 μg/kg) significantly reduced tumor growth; however, the combination of DON and TRAIL did not show a greater effect than DON alone.
Conclusions:
- Deoxynivalenol (DON) demonstrates potential in sensitizing prostate cancer cells to TRAIL-induced apoptosis in vitro.
- While DON alone exhibited anti-tumor effects in vivo, the combination with TRAIL was not superior.
- DON's ability to induce apoptosis warrants further research for potential therapeutic applications, possibly in different combination strategies.
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