6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells

Zhang, Xiaowei; Castanotto, Daniela; Nam, Sangkil; Horne, David; Stein, C. A.

doi:10.1016/j.ymthe.2016.10.017

Cited by 31 publications

(20 citation statements)

References 61 publications

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“…58 Recently, the kinase inhibitor 6-bromoindirubine-3′-monoxime decreased AR expression in prostate cancer cells via inhibition of both GSK-3α and GSK-3β. 59 The recruitment in a phase 1 study evaluating lithium, a known inhibitor of GSK-3 and its effect on localized prostate cancer, was completed with no published data as yet 60 (NCT02198859).…”

Section: Gsk-3β Role In Specific Cancersmentioning

confidence: 99%

Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses

Şahin

Eturi

Souza

et al. 2019

Cancer Biology & Therapy

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As a kinase at the crossroads of numerous metabolic and cell growth signaling pathways, glycogen synthase kinase-3 beta (GSK-3β) is a highly desirable therapeutic target in cancer. Despite its involvement in pathways associated with the pathogenesis of several malignancies, no selective GSK-3β inhibitor has been approved for the treatment of cancer. The regulatory role of GSK-3β in apoptosis, cell cycle, DNA repair, tumor growth, invasion, and metastasis reflects the therapeutic relevance of this target and provides the rationale for drug combinations. Emerging data on GSK-3β as a mediator of anticancer immune response also highlight the potential clinical applications of novel selective GSK-3β inhibitors that are entering clinical studies. This manuscript reviews the preclinical and early clinical results with GSK-3β inhibitors and delineates the developmental therapeutics landscape for this potentially important target in cancer therapy.

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Section: Gsk-3β Role In Specific Cancersmentioning

confidence: 99%

Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses

Şahin

Eturi

Souza

et al. 2019

Cancer Biology & Therapy

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“…BIO is a glycogen synthase kinase 3 (GSK-3) inhibitor and has neuroprotective and regenerative effects [43]. Zhang et al found that BIO significantly improves the targeting of antisense oligonucleotides (ASOs) in both the cell cytoplasm and the nucleus [44]. Furthermore, BIO enhances ASO function and represses AR expression through the inhibition of the two main GSK-3 isoforms: GSK-3 α and GSK-3 β activity [44].…”

Section: Resultsmentioning

confidence: 99%

“…Zhang et al found that BIO significantly improves the targeting of antisense oligonucleotides (ASOs) in both the cell cytoplasm and the nucleus [44]. Furthermore, BIO enhances ASO function and represses AR expression through the inhibition of the two main GSK-3 isoforms: GSK-3 α and GSK-3 β activity [44]. However, Kohler et al suggested that low-dose BIO induced increased neovascularization, secondary to VEGF, a process that was accompanied by a partial dedifferentiation of endothelial cells via β -catenin [45].…”

Section: Resultsmentioning

confidence: 99%

Competing Endogenous RNA and Coexpression Network Analysis for Identification of Potential Biomarkers and Therapeutics in association with Metastasis Risk and Progression of Prostate Cancer

Pang

Zhao

Wang

et al. 2019

Oxidative Medicine and Cellular Longevity

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Prostate cancer (PCa) is the most frequently diagnosed malignant neoplasm in men. Despite the high incidence, the underlying pathogenic mechanisms of PCa are still largely unknown, which limits the therapeutic options and leads to poor prognosis. Herein, based on the expression profiles from The Cancer Genome Atlas (TCGA) database, we investigated the interactions between long noncoding RNA (lncRNA) and mRNA by constructing a competing endogenous RNA network. Several competing endogenous RNAs could participate in the tumorigenesis of PCa. Six lncRNA signatures were identified as potential candidates associated with stage progression by the Kolmogorov-Smirnov test. In addition, 32 signatures from the coexpression network had potential diagnostic value for PCa lymphatic metastasis using machine learning algorithms. By targeting the coexpression network, the antifungal compound econazole was screened out for PCa treatment. Econazole could induce growth restraint, arrest the cell cycle, lead to apoptosis, inhibit migration, invasion, and adhesion in PC3 and DU145 cell lines, and inhibit the growth of prostate xenografts in nude mice. This systematic characterization of lncRNAs, microRNAs, and mRNAs in the risk of metastasis and progression of PCa will aid in the identification of candidate prognostic biomarkers and potential therapeutic drugs.

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“…A recent study has shown that the efficiency of oligonucleotide delivery in the absence of carriers can be improved by a small molecule, 6-bromo-indirubin-3’-oxime (6BIO). Five-fold less AR-target antisense oligonucleotide was required to achieve 50% reduction of AR protein expression in the presence of 6BIO compared with AR-target antisense oligonucleotide alone 16. The augmenting effect of 6BIO may be caused by its glycogen synthase kinase-3 (GSK-3)α/β inhibition activity.…”

Section: Concomitant Targeting Of the Ar Pathwaymentioning

confidence: 99%

Current opinion and mechanistic interpretation of combination therapy for castration-resistant prostate cancer

Qiu

2019

Asian J Androl

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Recent advances in genomics technology have led to the massive discovery of new drug targets for prostate cancer; however, none of the currently available therapeutics is curative. One of the greatest challenges is drug resistance. Combinations of therapies with distinct mechanisms of action represent a promising strategy that has received renewed attention in recent years. Combination therapies exert cancer killing functions through either concomitant targeting of multiple pro-cancer factors or more effective inhibition of a single pathway. Theoretically, the combination therapy can improve efficacy and efficiency compared with monotherapy. Although increasing numbers of drug combinations are currently being tested in clinical trials, the mechanisms by which these combinations can overcome drug resistance have yet to be fully understood. The purpose of this review is to summarize recent work on therapeutic combinations in the treatment of castration-resistant prostate cancer and discuss emerging mechanisms underlying drug resistance. In addition, we provide an overview of the current preclinical mechanistic studies on potential therapeutic combinations to overcome drug resistance.

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6BIO Enhances Oligonucleotide Activity in Cells: A Potential Combinatorial Anti-androgen Receptor Therapy in Prostate Cancer Cells

Cited by 31 publications

References 61 publications

Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses

Glycogen synthase kinase-3 beta inhibitors as novel cancer treatments and modulators of antitumor immune responses

Competing Endogenous RNA and Coexpression Network Analysis for Identification of Potential Biomarkers and Therapeutics in association with Metastasis Risk and Progression of Prostate Cancer

Current opinion and mechanistic interpretation of combination therapy for castration-resistant prostate cancer

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