Comparison of in vitro effects of the pure antiandrogens OH-flutamide, casodex, and nilutamide on androgen-sensitive parameters

Simard, Jacques; Singh, S. M.; Labrie, Fernand

doi:10.1016/s0090-4295(97)00029-0

Cited by 37 publications

(29 citation statements)

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“…In contrast, hormonal therapies promote tumor regression either by reducing the amount of androgens available to the tumor cells or by binding the AR to antagonize the cellular actions of androgens. 2 However, a more modern view of the endocrine response pathways retains the concept that androgens acting through ARs are central to the development of PCa, but also recognizes that it is naive to consider AR signaling as being isolated from the rest of the signals governing the cancer cell biology. Indeed, an increasing number of elements within the PCa phenotype, notably peptide growth factors, have been recognized as factors able to modify AR signaling.…”

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confidence: 99%

“…Hormonal therapy usually decreases the volume of primary and metastatic lesions by inducing apoptosis. 2 It is thought that tumor cells eventually circumvent the need for steroid hormones, allowing them to continue to grow and progress despite therapy. In fact, after this initial response, the tumors recur in an AI form that shows only a limited response to additional androgen withdrawal [5][6][7] and are partially resistant to cure by chemotherapy.…”

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confidence: 99%

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Retracted: Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro

Festuccia

Gravina

Angelucci

et al. 2005

Intl Journal of Cancer

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Progression from an androgen-dependent to an androgen-independent state often occurs in patients with prostate cancer (PCa) who undergo hormonal therapy. We have investigated whether inhibition of the epidermal growth factor receptor (EGFR) signaling pathway affects the antitumor effect of a nonsteroidal antiandrogen. Gefitinib (Iressa), an EGFR tyrosine kinase inhibitor, and bicalutamide (Casodex), a nonsteroidal antiandrogen [androgen receptor (AR) antagonist], were administered alone and in combination to AR-positive human PCa cell lines. FACS analysis showed lower EGFR expression levels on AR-positive cells (LNCaP, CWR22, CWR22R 2152 and AR-transfected DU145 cell lines) compared with AR-negative cells (DU145, PC3 and TSUPr1). Moreover, in AR-transfected DU145 cells, chronic treatment with bicalutamide increased EGFR expression to levels similar to androgen-independent DU145 cells. All AR-positive PCa cell lines were sensitive to gefitinib (IC 50 = 0.1-0.6 mM), whereas higher concentrations of bicalutamide were needed to reduce AR-positive PCa cell line proliferation (IC 50 = 0.8-2.0 mM). Low doses of gefitinib increased the antitumor effects of bicalutamide by strongly reducing the IC 50 of bicalutamide (approximately 10-fold). Similarly, bicalutamide increased the antiproliferative effects of gefitinib by reducing the IC 50 of gefitinib (approximately 5-fold). Taken together, our data suggest that in androgen-dependent cell lines, addition of gefitinib in combination with bicalutamide results in concurrent dual inhibition of AR and EGFR/HER2 pathways. This causes a significant delay in the onset of EGFRdriven androgen independence. ' 2005 Wiley-Liss, Inc. Key words: prostate cancer; hormonal therapy; EGFR; androgenindependent tumorsIn industrialized countries, prostate cancer (PCa) is the most frequently occurring malignancy in men, representing the second highest cause of cancer-related death. PCa usually begins as an androgen-sensitive, androgen-dependent (AD), nonmetastatic cancer, which without intervention may follow a gradual transition into a highly metastatic and then androgen-insensitive (AI) variety. The androgen receptor (AR) is a nuclear receptor that cooperates with multiple proteins to exert its biologic function. Upon binding to the ligand testosterone/5 -dihydrotestosterone (DHT), the AR can bind to the androgen response element (ARE) on the 5 0 promoter of target genes, resulting in the modulation of cell growth. Until relatively recent times, endocrine response pathways in PCa were described solely in terms of the intracellular pathways used by the androgens and the subsequent destructive effects exerted on AR signaling by antihormonal treatments. 1 It is widely accepted that androgens promote tumor growth by binding to ARs and acting as nuclear transcription factors that regulate the expression of genes involved in cell proliferation and survival mechanisms. In contrast, hormonal therapies promote tumor regression either by reducing the amount of androgens available to the tumor cells or...

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confidence: 99%

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confidence: 99%

Retracted: Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro

Festuccia

Gravina

Angelucci

et al. 2005

Intl Journal of Cancer

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“…Flutamide is converted in vivo to the more potent OHF by hepatic hydroxylation (156). While OHF is considered a pure AR antagonist in most tissues of the reproductive system, its effect on bone may be more ambiguous.…”

Section: Effects Of the Anti-androgen Hydroxyflutamide (Ohf) On Bone mentioning

confidence: 99%

Androgen effects on bone metabolism: recent progress and controversies

Hofbauer

Khosla

1999

European Journal of Endocrinology

120

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Androgens have beneficial effects on skeletal development and maintenance in women and men. The detection and functional characterization of androgen receptors in bone cells has implicated bone tissue as a potential target tissue for androgens. Gonadal and adrenal androgens directly regulate various aspects of osteoblastic lineage cells, including proliferation, differentiation, mineralization, and gene expression. These effects may differ depending on the stage of differentiation, the number of androgen receptors, and other inherent characteristics (species, site, cell biology) of the osteoblastic cell system. In addition, recent studies have suggested that some of the anabolic and anti-resorptive effects of androgens on bone may be mediated by regulation of autocrine and paracrine factors in the bone microenvironment, including transforming growth factor-b, insulin-like growth factors (and their binding proteins), and interleukin-6. This review summarizes the recent progress made in our knowledge of androgen receptor action, local androgen metabolism in bone, and direct and indirect effects of gonadal and adrenal androgens as well as androgen receptor antagonists on bone cells.

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“…Bicalutamide is a member of the non steroidal anti-androgen class of drugs [25]. This molecule, with respect to other anti-androgens as cyproterone acetate, has the advantage of higher potency and selective antagonistic properties [26]. We elected the dose of 25 mg/day which seem to be the lower effective dose.…”

Section: Methodsmentioning

confidence: 99%

Combined treatment with bicalutamide and anastrozole in a young boy with peripheral precocious puberty due to McCune-Albright Syndrome

et al. 2012

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Comparison of in vitro effects of the pure antiandrogens OH-flutamide, casodex, and nilutamide on androgen-sensitive parameters

Cited by 37 publications

References 10 publications

Retracted: Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro

Retracted: Additive antitumor effects of the epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib (Iressa), and the nonsteroidal antiandrogen, bicalutamide (Casodex), in prostate cancer cells in vitro

Androgen effects on bone metabolism: recent progress and controversies

Combined treatment with bicalutamide and anastrozole in a young boy with peripheral precocious puberty due to McCune-Albright Syndrome

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