The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines

Banerjee, Hirendra Nath; Vaughan, Deirdre; Boston, Ava; Thorne, Gabriel; Payne, Gloria; Sampson, Josiah; Manglik, Vinod; Olczak, Pola; Powell, Brent V.; Winstead, Angela; Shaw, Roosevelt; Mandal, Santosh K.

doi:10.4172/1948-5956.1000512

Cited by 6 publications

(4 citation statements)

References 14 publications

(18 reference statements)

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“…The selective cytotoxicity has also been shown for hypoxia cells [17]. [20]. For the best compound, RAC6, the cell death was nearly 70% in cancer cells and nearly 20% in normal cells.…”

Section: The Cytotoxic Effects Are Highly Selective For the Cancer Cellsmentioning

confidence: 81%

The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers

Collery¹,

Veena

Harikrishnan

et al. 2019

Invest New Drugs

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The rhenium(I)-diselenoether complex (Re-diSe) is a rhenium tricarbonyl-based drug chelated by a diselenoether ligand. In this work, we compared its inhibitory effects on the hormone-independent MDA-MB231cancer line and other different cancer cell lines after an exposure time of 72 h by MTT assays. The sensitivity of MDA-MB231 was in the same range than the hormone dependent MCF-7 breast cancer, the PC-3 prostate and HT-29 colon cancer cells, while the A549 lung and the HeLa uterine cancer cells were less sensitive. We compared the inhibitory effects of Re-diSe and of its diselenide ligand (di-Se) on MDAMB231 and a normal HEK-293 human embryonic cell line, after 72 h and 120 h of exposure. The cytotoxicity was also studied by flow cytometry using ethidium bromide assays, as well as the effects on the ROS production by DFCA-test, while the levels of TGF-β1, VEGF-A, IGF-1 were addressed by ELISA tests. The dose required to inhibit 50% of the proliferation (IC50) ofMDAMB231 breast cancer cells decreased with the time of exposure to 120 h, while the free ligand (di-Se) was found poorly active, demonstrating the important role of Re in this Re-diSe combination. The cytotoxic effects of Re-diSe were highly selective for cancer cells, with a significant increase of the number of dead cancer cells at 5 μM for an exposure time of 120 h, while normal cells were not affected. A remarkable and significant decrease of the production of ROS together with a decrease of VEGF-A, TGF-β1, and IGF-1 by the cancer cells were also observed when cancer cells were exposed to Re-diSe.

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“…The selective cytotoxicity has also been shown for hypoxia cells [17]. [20]. For the best compound, RAC6, the cell death was nearly 70% in cancer cells and nearly 20% in normal cells.…”

Section: The Cytotoxic Effects Are Highly Selective For the Cancer Cellsmentioning

confidence: 81%

The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers

Collery¹,

Veena

Harikrishnan

et al. 2019

Invest New Drugs

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“…Our preliminary findings could help in solving tumor associated macrophages formation and therapeutic interventions in the future, however more research needs to be done in elucidating the core canonical pathways involved and detailed studies of cellular mechanisms in formation of TAMs and novel drugs like Rhenium ligands in preventing TAM formation and rescue. [16]…”

Section: Discussionmentioning

confidence: 99%

Differential expression of efferocytosis and phagocytosis associated genes in tumor associated macrophages exposed to African American patient derived prostate cancer microenvironment

Banerjee

Krauss

Worthington

et al. 2019

JST

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Macrophages are the first line of defense in the cellular environment in response to any antigenic or foreign invasion. Since cancer cells express antigenic molecules and create a tumor microenvironment quite different from the normal cellular environment, macrophages will attack this cancer cells as foreign Invaders. However, the cancer cells adept their ability to suppress macrophage activity by secreting compounds/proteins through unknown mechanisms and train these macrophages to aid in tumorigenesis. These macrophages are commonly known as tumor associated macrophages (TAM). In this study, our goal was to find out key regulatory molecules involved in this conversion of cancer-fighting macrophages to cancer friendly macrophages. We used African American(AA) patient derived established human prostate cancer cells along with the human derived macrophages followed by Affymetrix cDNA microarray analysis. Microarray analysis of the PCa cell exposed macrophages revealed appreciable decrease in mRNA expression of several genes associated with phagocytosis process. Aberrant expression of several noncoding RNAs that control the expression of such phagocytosis associated molecules were also evident. Increased expression of oncogenic miR such as, miR-148, 615, 515, 130, 139 and markedly decreased expression of tumor suppressive miR’s MiR-3130, let7c,101,103, 383 were noted. Further, TARGET SCAN analysis demonstrated these differential expression of non-coding RNA’s causing down regulation of phagocytosis promoting genes elf5A, Meg3, Tubb5, Sparcl-1, Uch-1, Bsg(CD147), Ube2v, GULP, Stabilin 1 and Pamr1. There is an increase of RAP1GAP gene that causes concomitant decrease in the expression of tubulin genes that promote cytoskeletal assembly in forming phagosomes. In addition Ingenuity pathway analysis of the gene expression data also showed upregulation of antiphagocytic genes IL-10, CD 16, IL-18 and MMP-9. Some core canonical pathways showing physiology of cellular signaling obtained by data analyzed by the Ingenuity software is confirmed a very complex mechanism still to be deciphered involved in the biology of TAM formation by which the rogue cancer cells tame their enemies, the macrophages and actually make them their helper cells to survive and propagate in the tumor microenvironment and thus prepare for epithelial mesenchymal transition for future metastasis and cancer stem cell formation and progression.

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“…For example, pentylcarbonato Re(CO) 3 compounds induced significant cytotoxic effects at the dose of 10 M for an exposure time of 48h in HTB-12 human astrocytoma brain cancer cells but not against CRL-2005 rat astrocyte normal brain cells [78]. Re(CO) 3 acetylsalicylato complexes showed a very selective cytotoxicity on HTB-12 human astrocytoma brain cancer cell lines and glioblastoma multiforme D54 cell lines versus rat normal brain astrocyte cells [77]. Similarly, (salicylaldehyde semicarbazone)Re(CO) 3 , that was found to react with DNA guanosine by proton transfer from the phenolic OH group to N7 of guanosine, selectively induced apoptosis against MOLT-4 cells versus normal human fibroblasts [141].…”

Section: Selectivity Of Rhenium Compounds For Cancer Cell Linesmentioning

confidence: 99%

“…The recently described series of (polypyridyl)Re(CO) 3 complexes bearing axial acetylsalicylato ligand were shown by DFT calculations to display a planar configuration. The UV titration of these complexes showed that their absorbance decreased with addition of DNA without any red shift suggesting that these complexes did not follow intercalation mechanism but were more likely to bind to the minor grooves of the DNA double helix [77]. On the other hand, the structurally similar Re(CO 3 ) pentylcarbonato complexes in which each Re atom was tethered to a nearly planar polypyridyl aromatic ligand, were found to bind through an intercalation mechanism as evidenced by X-ray structure determinations and DFT calculations [78].…”

Section: Dna Effects Of Re Complexesmentioning

confidence: 99%

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

Collery¹,

Desmaële

Veena

2019

CPD

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Background: Many rhenium (Re) complexes with potential anticancer properties have been synthesized in the recent years with the aim to overcome the clinical limitations of platinum agents. Re(I) tricarbonyl complexes are the most common but Re compounds with higher oxidation states have also been investigated, as well as hetero-metallic complexes and Re-loaded self-assembling devices. Many of these compounds display promising cytotoxic and phototoxic properties against malignant cells but all Re compounds are still at the stage of preclinical studies. Methods: The present review focused on the rhenium based cancer drugs that were in preclinical and clinical trials were examined critically. The detailed targeted interactions and experimental evidences of Re compounds reported by the patentable and non-patentable research findings used to write this review. Results: In the present review, we described the most recent and promising rhenium compounds focusing on their potential mechanism of action including, phototoxicity, DNA binding, mitochondrial effects, oxidative stress regulation or enzyme inhibition. Many ligands have been described that modulating the lipophilicity, the luminescent properties, the cellular uptake, the biodistribution, and the cytotoxicity, the pharmacological and toxicological profile. Conclusion: Re-based anticancer drugs can also be used in targeted therapies by coupling to a variety of biologically relevant targeting molecules. On the other hand, combination with conventional cytotoxic molecules, such as doxorubicin, allowed to take into profit the targeting properties of Re for example toward mitochondria. Through the example of the diseleno-Re complex, we showed that the main target could be the oxidative status, with a down-stream regulation of signaling pathways, and further on selective cell death of cancer cells versus normal cells.

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The Effects of Synthesized Rhenium Acetylsalicylate Compounds on Human Astrocytoma Cell Lines

Cited by 6 publications

References 14 publications

The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers

The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers

Differential expression of efferocytosis and phagocytosis associated genes in tumor associated macrophages exposed to African American patient derived prostate cancer microenvironment

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

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