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An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Sulforaphane Combined with Vitamin D Induces Cytotoxicity Mediated by Oxidative Stress, DNA Damage, Autophagy, and
Katiuska Tuttis1, Ana Rita Thomazela Machado2, Patrick Wellington da Silva Santos2
1Department of Genetics, Ribeirão Preto School of Medicine, University of São Paulo-USP, Ribeirão Preto 14049-900, SP, Brazil.
Abstract:
Prostate cancer ranks second in incidence worldwide. To date, there are no available therapies to effectively treat advanced and metastatic prostate cancer. Sulforaphane and vitamin D alone are promising anticancer agents in vitro and in vivo, but their low bioavailability has limited their effects in clinical trials. The present study examined whether sulforaphane combined with vitamin D at clinically relevant concentrations improved the cytotoxicity of the compounds alone towards DU145 and PC-3 human prostate tumor cells. To assess the anticancer activity of this combination, we analyzed cell viability (MTT assay), oxidative stress (CM-H2DCFDA), autophagy (fluorescence), DNA damage (comet assay), and protein expression (Western blot). The sulforaphane-vitamin D combination (i) decreased cell viability, induced oxidative stress, DNA damage, and autophagy, upregulated BAX, CASP8, CASP3, JNK, and NRF2 expression, and downregulated BCL2 expression in DU145 cells; and (ii) decreased cell viability, increased autophagy and oxidative stress, upregulated BAX and NRF2 expression, and downregulated JNK, CASP8, and BCL2 expression in PC-3 cells. Therefore, sulforaphane and vitamin D in combination have a potential application in prostate cancer therapy, and act to modulate the JNK/MAPK signaling pathway.
Insights
Combining sulforaphane and vitamin D shows promise for treating advanced prostate cancer by enhancing cell death and modulating key cellular pathways. This combination therapy may overcome limitations of individual treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer is a leading global cancer with limited treatment options for advanced stages.
- Sulforaphane and vitamin D exhibit anticancer properties but suffer from low bioavailability.
- Existing therapies for metastatic prostate cancer are insufficient.
Purpose of the Study:
- To investigate the combined effect of sulforaphane and vitamin D on prostate cancer cells.
- To evaluate if the combination enhances cytotoxicity compared to individual agents.
- To explore the underlying molecular mechanisms of the combined treatment.
Main Methods:
- Cell viability was assessed using the MTT assay.
- Oxidative stress was measured with CM-H2DCFDA.
- Autophagy and DNA damage were analyzed via fluorescence and comet assays, respectively.
- Protein expression was determined using Western blot analysis.
Main Results:
- The combination significantly decreased cell viability in DU145 and PC-3 cells.
- It induced oxidative stress, DNA damage, and autophagy in DU145 cells.
- Upregulation of BAX, CASP3, CASP8, and NRF2, and downregulation of BCL2 were observed in DU145 cells.
- In PC-3 cells, the combination increased autophagy and oxidative stress, upregulated BAX and NRF2, and downregulated JNK, CASP8, and BCL2.
Conclusions:
- Sulforaphane and vitamin D in combination demonstrate potential as a prostate cancer therapy.
- The synergistic effect involves modulation of the JNK/MAPK signaling pathway.
- This combination may offer a novel therapeutic strategy for advanced prostate cancer.
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