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Investigating the Anticancer Effects of Sulforaphane in an In Vitro Coculture Model of Prostate Cancer Cells with
Jane In den Birken1,2, Laura Rathjens1,2, Hannah Münch1,2
1Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
Abstract:
Sulforaphane (SFN) is a phytoderived compound abundant in cruciferous plants that possesses a broad spectrum of anticancer properties. We showed that SFN-induced caspase-mediated apoptosis in grade IV bone metastasis-derived androgen-insensitive PC-3 (IC50 = 4.2 μM), and lymph node metastasis-derived androgen-sensitive LNCaP (IC50 = 2.8 μM) prostate adenocarcinoma cells. SFN-mediated cardiotoxic side effects were tested in a preclinical in vitro model that enables the study simultaneously of the impact of drugs on cancer cell death and contractile properties of engineered heart tissues generated from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM EHT). Thereby, SFN exposure induced PC-3 cell death without affecting the contractile force of hiPSC-CM EHT. Interestingly, the irregular beating pattern of hiPSC-CM EHT observed in the presence of PC-3 coculture was normalized compared to vehicle treatment. Overall, this in vitro coculture model of hiPSC-CM EHT and cancer cells could facilitate the study of cardiotoxic cancer drug side-effects.
Insights
Sulforaphane (SFN) effectively induces cancer cell death in prostate adenocarcinoma models. This study demonstrates SFN
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- Sulforaphane (SFN), a natural compound from cruciferous vegetables, exhibits anticancer potential.
- Prostate cancer cells, including androgen-insensitive PC-3 and androgen-sensitive LNCaP, are targeted.
- Assessing drug-induced cardiotoxicity alongside anticancer effects is crucial for therapeutic development.
Purpose of the Study:
- To evaluate the efficacy of SFN in inducing apoptosis in prostate cancer cells.
- To investigate the cardiotoxic side effects of SFN using a human-induced pluripotent stem cell-derived cardiomyocyte engineered heart tissue (hiPSC-CM EHT) model.
- To explore the utility of a co-culture system for simultaneous assessment of anticancer activity and cardiotoxicity.
Main Methods:
- Utilized in vitro models to test SFN's impact on PC-3 and LNCaP prostate cancer cells.
- Employed a preclinical hiPSC-CM EHT model to assess SFN's effects on cardiomyocyte contractility.
- Established a co-culture system combining hiPSC-CM EHT with prostate cancer cells for integrated drug testing.
Main Results:
- SFN induced caspase-mediated apoptosis in both PC-3 (IC50 = 4.2 μM) and LNCaP (IC50 = 2.8 μM) cells.
- SFN treatment led to PC-3 cell death without compromising the contractile force of hiPSC-CM EHT.
- Co-culture with PC-3 cells normalized irregular hiPSC-CM EHT beating patterns compared to vehicle controls.
Conclusions:
- SFN demonstrates potent anticancer effects against prostate cancer cells in vitro.
- SFN exhibits a favorable safety profile regarding cardiotoxicity in the preclinical hiPSC-CM EHT model.
- The developed in vitro co-culture model is a valuable tool for evaluating cardiotoxic side effects of anticancer drugs.
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