Investigating the Anticancer Effects of Sulforaphane in an In Vitro Coculture Model of Prostate Cancer Cells with Engineered Heart Tissue
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.
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