Pharmacological Development of Target-Specific Delocalized Lipophilic Cation-Functionalized Carboranes for Cancer Therapy

Tseligka, Eirini D.; Rova, Aikaterini; Amanatiadou, Elsa P.; Calabrese, Giuseppe; Tsibouklis, John; Fatouros, Dimitrios G.; Vizirianakis, Ioannis S.

doi:10.1007/s11095-016-1930-4

Cited by 20 publications

(28 citation statements)

References 46 publications

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“…Similarly, RT-qPCR analysis was performed with MCF-7 and MRC-5 cultures exposed to VDS58; however, no alterations in gene expression levels were recorded between treated and untreated cells (data not shown). Notably, within the panel of genes analyzed in MRC-5 cells, only CDK2, CDK6, BAD, BAX and BCL2 appeared to have been amplified by RT-qPCR, as also reported in our recent study (22).…”

Section: Assessment Of Vds58 Cytotoxicity Profile In Varioussupporting

confidence: 87%

“…. The previously established cancer U-87 MG, MCF-7, murine erythroleukemia FLC clone 745 (MEL-745) and K562 cell lines, and a normal MRC-5 cell line, were obtained, stored and used in a routine manner (22,23) in the Laboratory of Pharmacology, School of Pharmacy, Aristotle University of Thessaloniki (Greece) (<25 passages were applied). The murine erythroleukemia MEL-745 cells were obtained from Dr C. Friend (Division of Cytology, The Sloan-Kettering Institute for Cancer Research, New York, NY, USA) (24) and were cultured as described by our previous study (25).…”

Section: Synthesis Of Natural Sesquiterpenoids and Analogsmentioning

confidence: 99%

“…RNA isolation from U-87 MG and K562 cells, and the two-step RT-qPCR analysis (kit KK4602; Kapa Biosystems, Wilmington, MA, USA) were performed as previously described (22). The following primer sequences were used to amplify the indicated genes: β-actin (ACTB) forward, 5'-ttgctgacaggatgcagaag-3' and reverse, 5'-tgatccacatctgctggaag-3'; BCL2 associated X apoptosis regulator (BAX) forward, 5'-tctgacggcaacttcaactg-3' and reverse, 5'-gaggaagtccaatgtccagc-3'; BCL2 apoptosis regulator (BCL2) forward, 5'-acttcgccgagatgtcca-3' and reverse, 5'-caaagaaggcc acaatcctc-3'; CDKN1 forward, 5'-gagcgatggaacttcgactt-3' and reverse, 5'-gtgggaaggtagagcttggg-3'; CASP9 forward, 5'-tcgaagc caaccctagaaaa-3' and reverse, 5'-cctccagaaccaatgtccac-3'; BAD forward, 5'-cagatcccagagtttgagcc-3' and reverse, 5'-ctgctcctgctg gtgactg-3'; CASP3 forward, 5'-ggttcatccagtcgctttgt-3' and reverse, 5'-aattctgttgccacctttcg-3'; CDK4 forward, 5'-accagatggcactta caccc-3' and reverse, 5'-ccacagaagagaggctttcg-3'; CDK2 forward, 5'-ttgtcaagctgctggatgtc-3' and reverse, 5'-tgatgaggggaagagga atg-3'; CDK6 forward, 5'-tgcacagtgtcacgaacaga-3' and reverse, 5'-acctcggagaagctgaaaca-3'; cyclin D1 (CCND1) forward, 5'-ctgc gaagtggaaaccatc-3' and reverse, 5'-ttgaagtaggacaccgaggg-3'; CASP8 forward, 5'-gatgacatgaacctgctgga-3' and reverse, 5'-cag gctcttgttgatttggg-3'; MYC forward, 5'-aggagaatgtcaagaggcga-3' and reverse, 5'-ggccttttcattgttttcca-3'; catenin β1 (CTNNB1) forward, 5'-gctgggaccttgcataacctt-3' and reverse, 5'-attttcac cagggcaggaatg-3'; RB transcriptional corepressor 1 (RB1) forward, 5'-tgtcagagagagagcttggt-3' and reverse, 5'-ctcatctaggtcaactgctgc-3'; and transforming growth factor β1 (TGFB1) forward, 5'-actgcg gatctctgtgtcattg-3' and reverse, 5'-acagtagtgttccccactggtc-3' .…”

Section: Rna Extraction and Reverse Transcription-quantitative Polymementioning

confidence: 99%

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Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

et al. 2018

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The present study aimed to assess the pharmacological anticancer profile of three natural and five synthetic sesquiterpenes developed by total chemical synthesis. To this end, their properties at the cellular and molecular level were evaluated in a panel of normal and cancer cell lines. The results obtained by performing cytotoxicity assays and gene expression analysis by reverse transcription-quantitative polymerase chain reaction showed that: i) Among the sesquiterpene derivatives analyzed, VDS58 exhibited a notable anticancer profile within attached (U-87 MG and MCF-7) and suspension (K562 and MEL-745) cancer cell cultures; however, U-87 MG cells were able to recover their proliferation capacity rapidly after 48 h of exposure; ii) gene expression profiling of U-87 MG cells, in contrast to K562 cells, showed a transient induction of cyclin-dependent kinase inhibitor 1A (CDKN1) expression; iii) the expression levels of transforming growth factor β1 (TGFB1) increased after 12 h of exposure of U-87 MG cells to VDS58 and were maintained at this level throughout the treatment period; iv) in K562 cells exposed to VDS58, TGFB1 expression levels were upregulated for 48 h and decrease afterwards; and v) the re-addition of VDS58 in U-87 MG cultures pretreated with VDS58 resulted in a notable increase in the expression of caspases (CASP3 and CASP9), BCL2‑associated agonist of cell death (BAD), cyclin D1, CDK6, CDKN1, MYC proto-oncogene bHLH transcription factor (MYC), TGFB1 and tumor suppressor protein p53. This upregulation persisted only for 24 h for the majority of genes, as afterwards, only the expression of TGFB1 and MYC was maintained at high levels. Through bioinformatic pathway analysis of RNA-Seq data of parental U-87 MG and K562 cells, substantial variation was reported in the expression profiles of the genes involved in the regulation of the cell cycle. This was associated with the differential pharmacological profiles observed in the same cells exposed to VDS58. Overall, the data presented in this study provide novel insights into the molecular mechanisms of action of sesquiterpene derivatives by dysregulating the expression levels of genes associated with the cell cycle of cancer cells.

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Section: Assessment Of Vds58 Cytotoxicity Profile In Varioussupporting

confidence: 87%

Section: Synthesis Of Natural Sesquiterpenoids and Analogsmentioning

confidence: 99%

Section: Rna Extraction and Reverse Transcription-quantitative Polymementioning

confidence: 99%

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Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

et al. 2018

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“… 6 – 8 Owing to the capability of recently developed BNCT agents to target cancer cells, including CSCs, both efficiently and selectively, the clinical use of these agents may be characterized by low incidence drug resistance profiles. 9 , 10 …”

Section: Introductionmentioning

confidence: 99%

Boron-containing delocalised lipophilic cations for the selective targeting of cancer cells

et al. 2017

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“…Alternatively, ionic boronated structure may have an inherent affinity for cancer cells. To further explore these findings, Tseligka axis [132].…”

Section: Delocalized Lipophilic Cationsmentioning

confidence: 99%

Towards carborane-functionalised structures for the treatment of brain cancer

Calabrese

Daou

Barbu

et al. 2018

Drug Discovery Today

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Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness. Here, we review progress in the molecular design of recently investigated carborane derivatives in light of the widely accepted performance requirements for effective BNCT.

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Pharmacological Development of Target-Specific Delocalized Lipophilic Cation-Functionalized Carboranes for Cancer Therapy

Cited by 20 publications

References 46 publications

Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

Uncovering the pharmacological response of novel sesquiterpene derivatives that differentially alter gene expression and modulate the cell cycle in cancer cells

Boron-containing delocalised lipophilic cations for the selective targeting of cancer cells

Towards carborane-functionalised structures for the treatment of brain cancer

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