The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. A critical factor contributing to its incidence and development is the presence of prostate cancer stem cells (PCSCs). Targeting PCSCs has become key in enhancing therapeutic and clinical outcomes of prostate cancer. Sulforaphane (SFN), a compound found in cruciferous vegetables, has shown effective antineoplastic activity in prostate cancer. Yet, its mechanisms of action in PCSCs remains unclear. In the present study, tumorsphere formation assay was used to isolate and enrich PCSCs from PC-3 cells. Our results found that SFN effectively reduced the activity of PCSCs, including the ability of tumorsphere formation, the number of CD133 positive cells, and the expression of PCSCs markers. Moreover, the data showed that SFN inhibited PCSCs through downregulating the activation of Wnt/β-catenin and hedgehog signaling pathways in PCSCs. Furthermore, the verification experiments showed that the activators of Wnt/β-catenin (LiCl) and hedgehog (purmorphamine) attenuated the effects of SFN on PCSCs, including the expression of stem cell markers, cell proliferation and apoptosis. Meanwhile, suppression of β-catenin or Smoothened enhanced the effects of SFN on PCSCs. In addition, molecular docking further indicated that SFN inhibited Wnt/β-catenin and hedgehog pathways by directly targeting β-catenin and Smoothened. Taken together, our results demonstrated that SFN targeted PCSCs through Wnt/β-catenin and hedgehog pathways to inhibit stemness and proliferation and induce apoptosis. Findings from this study could provide new insights into SFN as a dietary supplement or adjunct to chemotherapy.
Keywords: Cancer stem cells; Hedgehog; Prostate cancer; Sulforaphane; Wnt/β-catenin.
Copyright © 2024 Elsevier Inc. All rights reserved.