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or c-Jun (Fig. 5). However, 3-DSC needs more evaluation in animal experiments. Overall, the results of the present study have identified 3-DSC as a natural compound that inhibits growth and induces apoptosis in colorectal cancer E 64 by directly targeting TOPK and its down-stream eﬀectors. This suggests that 3-DSC could be a useful che-motherapeutic agent against human colon cancers.
Conflict of interest
The authors declare that they have no conflicts of interest.
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Laboratory-Prostate cancer Cell-based evidence regarding the role of FSH in prostate cancer
NishtmanD1X Dizeyi, PhD2X.D.a,*, Dorota3X Trzybulska, PhD4X.D.a, YahiaD5X Al-Jebari, MD6X.Engb, IlpoD7X Huhtaniemi, PhD8X.D.c, YvonneD9X Lundberg Giwercman, PhD10X.D.a
a Department of Translational Medicine, Molecular Genetic Reproductive Medicine, Lund University, Malmo,€ Sweden
b Department of Translational Medicine,Molecular Reproductive Medicine, Lund University, Malmo,€ Sweden c Department of Surgery & Cancer, Imperial College, London, UK
Introduction: Conversion of androgen-responsive prostate cancer (CaP) to castration-resistant CaP is associated with an acceleration of the disease that often requires treatment modalities other than androgen deprivation therapy only. Recently, follicle-stimulating hormone (FSH) has been shown to play a role in CaP growth, and clinical data showed that high serum concentration of FSH in chemically castrated CaP patients was associated with a shorter time of progression to castration-resistant CaP. In this study, we sought to investigate if FSH could have direct effects on CaP cells, possibly through the androgen receptor and androgen receptor regulated genes, such as prostate-specific antigen (PSA).
Materials and methods: The human CaP cell lines PC-3, LNCaP and C4-2, and nonmalignant PNT1A cells, were utilized to investigate the effects of FSH. qPCR, Western blotting analysis, and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymetoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium assays were performed in order to analyze the FSH effects.
Results: The FSH receptor was present in all cell lines except PNT1A. FSH significantly increased PSA mRNA (P < 0.01) and protein (P < 0.03) levels in C4-2 cells in a dose-dependent manner. In LNCaP cells, FSH also increased PSA protein level, although to a lesser extent than in C4-2 cells, and the expression was reduced by the antiandrogen enzalutamide. In PC-3 cells, FSH was shown to increase their proliferation (P < 0.03) and b-catenin expression.
Conclusion: These findings demonstrate that FSH may have a direct effect in CaP in an androgen-depleted environment. However, further research is needed to understand the significance of direct FSH action in the maintenance of CaP growth at the different phases of transition from androgen dependence to androgen independence. 2018 Elsevier Inc. All rights reserved.
Keywords: Follicle-stimulating hormone receptor; Prostate-specific antigen; Signaling pathway; Castration-resistant prostate cancer
Androgen deprivation therapy (ADT) is the cornerstone in the treatment of metastatic prostate cancer (CaP). Ini-tially, tumors regress and prostate-specific antigen (PSA) level declines following ADT in the majority of patients. However, despite tumor regression, patients eventually invariably develop castration-resistant CaP (CRCaP) . The mechanisms suggested to relate to this state of disease