Casein kinase 2 inhibition attenuates androgen receptor function and cell proliferation in prostate cancer cells

Yao, Kai; Youn, Hyewon; Gao, Xiaoyan; Huang, Bi‐Jun; Zhou, Fangjian; Li, Benyi; Han, Hui

doi:10.1002/pros.22493

Cited by 22 publications

(22 citation statements)

References 29 publications

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“…1 Overexpression of CK2 and its elevated activity are closely related to many human cancers, including breast, 2 lung, 3 pancreas, 4 and prostate. 5 Recent studies also confirmed CK2 as a key target in leukemia, 6 and glioblastoma. 7 One of the most remarkable features of CK2 is the existence of several forms: (i) catalytic CK2α subunit and its isoforms CK2α' and CK2α", (ii) regulatory CK2β subunit, and (iii) heterotetramer composed of two catalytic subunits and two regulatory subunits.…”

Section: Introductionmentioning

confidence: 92%

Converting Potent Indeno[1,2-b]indole Inhibitors of Protein Kinase CK2 into Selective Inhibitors of the Breast Cancer Resistance Protein ABCG2

et al. 2014

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A series of indeno[1,2-b]indole-9,10-dione derivatives were synthesized as human casein kinase II (CK2) inhibitors. The most potent inhibitors contained a N(5)-isopropyl substituent on the C-ring. The same series of compounds was found to also inhibit the breast cancer resistance protein ABCG2 but with totally different structure-activity relationships: a N(5)-phenethyl substituent was critical, and additional hydrophobic substituents at position 7 or 8 of the D-ring or a methoxy at phenethyl position ortho or meta also contributed to inhibition. The best ABCG2 inhibitors, such as 4c, 4h, 4i, 4j, and 4k, behaved as very weak inhibitors of CK2, whereas the most potent CK2 inhibitors, such as 4a, 4p, and 4e, displayed limited interaction with ABCG2. It was therefore possible to convert, through suitable substitutions of the indeno[1,2-b]indole-9,10-dione scaffold, potent CK2 inhibitors into selective ABCG2 inhibitors and vice versa. In addition, some of the best ABCG2 inhibitors, which displayed a very low cytotoxicity, thus giving a high therapeutic ratio, and appeared not to be transported, constitute promising candidates for further investigations.

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Section: Introductionmentioning

confidence: 92%

Converting Potent Indeno[1,2-b]indole Inhibitors of Protein Kinase CK2 into Selective Inhibitors of the Breast Cancer Resistance Protein ABCG2

et al. 2014

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“…It is one of the most highly referenced substances used for cytotoxicity and viability assays; PubMed records list over 200 publications citing Alamar Blue (resazurin) and cancer research and over 1,000 publications in drug screening, development and discovery. Generally, its use has been applied to various aspects of monitoring cellular health [1,2], apoptosis, cell cycle function and control [3–8], test compound toxicology in medicine and in environmental risk assessments [9–13], cytotoxicity [14–16] and antimicrobial susceptibility testing [17,18]. It has also been used to assess various bacteria, yeast and fungal species and different cell types including, but not limited to fibroblasts [19], immortalized and cancer cell lines [9,20,21], mouse and human lymphocytes [1,22], primary neuronal cell culture [4], and various animal cell lines [23,24].…”

Section: Introductionmentioning

confidence: 99%

Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays

Rampersad

2012

Sensors

794

555

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Accurate prediction of the adverse effects of test compounds on living systems, detection of toxic thresholds, and expansion of experimental data sets to include multiple toxicity end-point analysis are required for any robust screening regime. Alamar Blue is an important redox indicator that is used to evaluate metabolic function and cellular health. The Alamar Blue bioassay has been utilized over the past 50 years to assess cell viability and cytotoxicity in a range of biological and environmental systems and in a number of cell types including bacteria, yeast, fungi, protozoa and cultured mammalian and piscine cells. It offers several advantages over other metabolic indicators and other cytotoxicity assays. However, as with any bioassay, suitability must be determined for each application and cell model. This review seeks to highlight many of the important considerations involved in assay use and design in addition to the potential pitfalls.

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“…In addition, the androgen-independent prostate cancer cell line PC-3 also displays relatively elevated CK2 activity compared to LNCaP prostate cells [19, 20]. In accordance with these observations, targeting CK2α with antisense RNA or inhibitors induces tumor shrinkage in a human prostate cancer xenograft model, suggesting the importance of CK2 in prostate tumorigenesis [3, 21, 22]. Although the importance of CK2 in tumor cell survival and growth is clear, the molecular mechanism by which CK2 is involved in prostate tumorigenesis has not been extensively investigated.…”

Section: Introductionmentioning

confidence: 79%

CK2-NCoR signaling cascade promotes prostate tumorigenesis

et al. 2013

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The aberrant expressions of casein kinase 2 (CK2) was found in prostate cancer patient and cell lines, but little is known of the detailed mechanisms implicated in prostate tumorigenesis. In this study, we report that both CK2 activity and CK2-mediated NCoR phosphorylation are significantly elevated in the androgen-independent prostate cancer cell line DU145 and PC-3 compared with RWPE1 and LNCaP cells. Increased phosphorylation inversely correlates with the mRNA level of the NCoR-regulated gene, interferon-γ-inducible protein 10 (IP-10). CK2 inhibition abrogated NCoR phosphorylation, IP-10 transcriptional repression, and the invasion activity of PC-3 cells. Inhibition of the CK2-NCoR network significantly reduced in vivo PC-3 cell tumorigenicity, likely due to transcriptional derepression of IP-10. Clinicopathological analyses revealed that increased CK2-mediated NCoR phosphorylation significantly correlates with poor survival among prostate cancer patients. These findings elucidate a CK2-modulated oncogenic cascade in prostate tumorigenesis.

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Casein kinase 2 inhibition attenuates androgen receptor function and cell proliferation in prostate cancer cells

Abstract: CK2 subunits α and α' are likely involved in AR signaling, and TBCA might be useful in the management of prostate cancers as a chemo-preventive agent in the future.

Cited by 22 publications

References 29 publications

Converting Potent Indeno[1,2-b]indole Inhibitors of Protein Kinase CK2 into Selective Inhibitors of the Breast Cancer Resistance Protein ABCG2

Converting Potent Indeno[1,2-b]indole Inhibitors of Protein Kinase CK2 into Selective Inhibitors of the Breast Cancer Resistance Protein ABCG2

Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays

CK2-NCoR signaling cascade promotes prostate tumorigenesis

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