Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055

Dueregger, Andrea; Guggenberger, Fabian; Barthelmes, Jan; Stecher, G.; Schuh, Markus; Intelmann, Daniel; Abel, G.; Haunschild, Jutta; Klocker, Helmut; Ramoner, Reinhold; Sampson, Natalie

doi:10.1016/j.phymed.2013.07.009

Cited by 13 publications

(10 citation statements)

References 21 publications

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“…The human telomerase reverse transcriptase‐immortalized benign prostate epithelial cell line EP156T has been described previously . Cells were maintained according to the distributor's instructions at 37°C in a humidified atmosphere with 5% CO 2 , as described . For production of lentiviral particles, HEK293‐T cells were maintained in DMEM containing 2 mM L ‐glutamine, 100 units/mL penicillin, 0.1 mg/mL streptomycin and 10% (w/v) fetal bovine serum (heat inactivated).…”

Section: Methodsmentioning

confidence: 99%

ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

Höll

Kozieł

Schäfer

et al. 2015

Molecular Carcinogenesis

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Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of male cancer death in Western nations. Thus, new treatment modalities are urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other tissues. However, the identity of the Nox enzyme(s) involved in prostate carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue samples and benign and malignant prostate epithelial cell lines identified Nox5 as an abundantly expressed Nox isoform. Consistently, immunohistochemical staining of a human PCa tissue microarray revealed distinct Nox5 expression in epithelial cells of benign and malignant prostatic glands. shRNA‐mediated knockdown of Nox5 impaired proliferation of Nox5‐expressing (PC‐3, LNCaP) but not Nox5‐negative (DU145) PCa cell lines. Similar effects were observed upon ROS ablation via the antioxidant N‐acetylcysteine confirming ROS as the mediators. In addition, Nox5 silencing increased apoptosis of PC‐3 cells. Concomitantly, protein kinase C zeta (PKCζ) protein levels and c‐Jun N‐terminal kinase (JNK) phosphorylation were reduced. Moreover, the effect of Nox5 knockdown on PC‐3 cell proliferation could be mimicked by pharmacological inhibition of JNK. Collectively, these data indicate that Nox5 is expressed at functionally relevant levels in the human prostate and clinical PCa. Moreover, findings herein suggest that Nox5‐derived ROS and subsequent depletion of PKCζ and JNK inactivation play a critical role in modulating intracellular signaling cascades involved in the proliferation and survival of PCa cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc.

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Section: Methodsmentioning

confidence: 99%

ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

Höll

Kozieł

Schäfer

et al. 2015

Molecular Carcinogenesis

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“…Cells were seeded into 96 well plates over night before addition of the substances at indicated concentrations. Cell viability was assessed after 72 h by WST-1 assay (Roche, Basel, Switzerland) as described in detail previously [ 27 ].…”

Section: Methodsmentioning

confidence: 99%

Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate

et al. 2015

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Tumor cells adapt via metabolic reprogramming to meet elevated energy demands due to continuous proliferation, for example by switching to alternative energy sources. Nutrients such as glucose, fatty acids, ketone bodies and amino acids may be utilized as preferred substrates to fulfill increased energy requirements. In this study we investigated the metabolic characteristics of benign and cancer cells of the prostate with respect to their utilization of medium chain (MCTs) and long chain triglycerides (LCTs) under standard and glucose-starved culture conditions by assessing cell viability, glycolytic activity, mitochondrial respiration, the expression of genes encoding key metabolic enzymes as well as mitochondrial mass and mtDNA content. We report that BE prostate cells (RWPE-1) have a higher competence to utilize fatty acids as energy source than PCa cells (LNCaP, ABL, PC3) as shown not only by increased cell viability upon fatty acid supplementation but also by an increased ß-oxidation of fatty acids, although the base-line respiration was 2-fold higher in prostate cancer cells. Moreover, BE RWPE-1 cells were found to compensate for glucose starvation in the presence of fatty acids. Of notice, these findings were confirmed in vivo by showing that PCa tissue has a lower capacity in oxidizing fatty acids than benign prostate. Collectively, these metabolic differences between benign and prostate cancer cells and especially their differential utilization of fatty acids could be exploited to establish novel diagnostic and therapeutic strategies.

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“…There is a lack of scientific evidence regarding its proposed estrogenic activity. However, it was recently shown to attenuate nucleoside uptake into cells and thus may have an impact on tumor treatment by nucleoside analogs [ 118 ]. One may speculate that its modulation of adenosine signaling may be beneficial for CV side effects of ADT [ 119 ], but this has yet to be investigated.…”

Section: Dietary Supplementsmentioning

confidence: 99%

The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

et al. 2014

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Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.

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Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055

Cited by 13 publications

References 21 publications

ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

Differential Utilization of Dietary Fatty Acids in Benign and Malignant Cells of the Prostate

The Use of Dietary Supplements to Alleviate Androgen Deprivation Therapy Side Effects during Prostate Cancer Treatment

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