Inhibition of steryl sulfatase activity in LNCaP human prostate cancer cells

Selcer, Kyle W.; Kabler, Heidi; Sarap, Jennifer L; Xiao, Zili; Li, Pui-Kai

doi:10.1016/s0039-128x(02)00030-2

Cited by 37 publications

(28 citation statements)

References 36 publications

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“…It was reported that DHEAS is hydrolyzed by STS in LNCaP cells [27] and the expression of STS is increased in prostate cancer cells, compared to non-malignant prostate tissues, as determined by immunohistochemical staining [28]. In the present study, expression of STS mRNA was detected in LNCaP cells, and this expression was not affected under androgen-depleted conditions ( Figure 1C).…”

Section: Contribution Of Oatp1a2 To Dheas-induced Cell Growth In Lncasupporting

confidence: 64%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

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The biological mechanisms underlying castration resistance of prostate cancer are not fully understood. In the present study, we examined the role of organic anion transporting polypeptides (OATPs) as importers of dehydroepiandrosterone sulfate (DHEAS) into cells to support growth under androgen-depleted conditions. Cell growth and mRNA expression of OATP genes were studied in human prostate cancer LNCaP and 22Rv1 cells under androgen-depleted conditions. The stimulatory effect of DHEAS on cell growth was investigated in LNCaP cells in which OATP1A2 had been silenced. Growth of both cell lines was stimulated by DHEAS and the effect was attenuated by STX64, an inhibitor of steroid sulfatase which can covert DHEAS to DHEA. OATP1A2 mRNA expression was increased most prominently among various genes tested in LNCaP cells grown in androgen-depleted medium. Similar results were obtained with 22Rv1 cells. Furthermore, the characteristics of

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Section: Contribution Of Oatp1a2 To Dheas-induced Cell Growth In Lncasupporting

confidence: 64%

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Arakawa

Nakanishi

Yanagihara

et al. 2012

Biochemical Pharmacology

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“…STS activity is present in prostatic tissue and in LNCaP cells, which were derived from prostatic cancer tissue [18,19]. In men with prostate cancer, castration results in only a 50% reduction in prostatic tissue concentrations of dihydrotestosterone [20].…”

Section: Sts Inhibitors In Prostate and Endometrial Cancersmentioning

confidence: 99%

Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer

et al. 2007

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Key Words. Breast cancer • Estrogen • Estrone sulfate • Steroid sulfatase • Sulfatase inhibitor LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Discuss the role of steroid sulfatase in regulating estrogen production in postmenopausal women.2. Describe the potential of steroid sulfatase inhibition in cancer therapy.3. Discuss a potential new endocrine therapy for patients progressing on aromatase.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACTInhibitors of steroid sulfatase are being developed as a novel therapy for hormone-dependent breast cancer in postmenopausal women. Data suggest that steroid sulfatase (STS) activity is much higher than aromatase activity in breast tumors and high levels of STS mRNA expression in tumors are associated with a poor prognosis. STS hydrolyzes steroid sulfates, such as estrone sulfate and dehydroepiandrosterone sulfate (DHEAS), to estrone and DHEA, which can be converted to steroids with potent estrogenic properties, that is, estradiol and androstenediol, respectively. Several potent irreversible STS inhibitors have now been identified, including STX64 (BN83495), a tricyclic sulfamate ester. This drug recently completed the first-ever trial of this new type of therapy in postmenopausal women with estrogen receptor-positive metastatic breast cancer. STX64, tested at 5-mg and 20-mg doses, was able to almost completely block STS activity in peripheral blood lymphocytes and tumor tissues. Inhibition of STS activity was associated with significant reductions in serum concentrations of androstenediol and estrogens. Unexpectedly, serum androstenedione concentrations also decreased by up to 86%, showing that this steroid, which is the main substrate for the aromatase in postmenopausal women, is derived mainly from the peripheral conversion of DHEAS. Of eight patients who completed therapy, five showed evidence of stable disease for up to 7.0 months. This new endocrine therapy offers considerable potential for the treatment of hormone-dependent breast cancer in postmenopausal women.

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“…Arylsulfamates have shown high potency as inhibitors of steroid sulfatase (STS) [7][8][9][10], an important therapeutic target for the treatment of hormone-sensitive diseases such as breast, endometrium and prostate cancers [11,12] in addition to acne and alopecia [13]. STS inhibitors could also have potential in the treatment of Alzheimer's disease through an increase in the level of dehydroepiandrosteronesulfate, a substrate of STS in the brain [14].…”

Section: Introductionmentioning

confidence: 99%

A Sequential Dual Cleavage of the Arylsulfamate Linker to Provide Both Sulfamate and Phenol Derivatives

Fournier¹,

Ciobanu²,

Poirier³

2015

ChemJMold

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Abstract. Tyramine sulfamate was linked to the trityl chloride resin and this polymeric solid support used to introduce two levels of molecular diversity by formation of peptide bonds. A dual cleavage strategy next generated in a sequential way (without resin split) two different types of compounds (phenol and arylsulfamate derivatives), which are therapeutically attractive types of compounds. Here, we used tyramine as a general scaffold, but other arylsulfamate derivatives could be judiciously used to extend the nature of synthesized compounds.

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Inhibition of steryl sulfatase activity in LNCaP human prostate cancer cells

Cited by 37 publications

References 36 publications

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Enhanced expression of organic anion transporting polypeptides (OATPs) in androgen receptor-positive prostate cancer cells: Possible role of OATP1A2 in adaptive cell growth under androgen-depleted conditions

Steroid Sulfatase: A New Target for the Endocrine Therapy of Breast Cancer

A Sequential Dual Cleavage of the Arylsulfamate Linker to Provide Both Sulfamate and Phenol Derivatives

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