459 Validation of a cell panel for preclinical evaluation of antitumor efficacy and toxicity of anticancer agents

Poly(A) polymerase (PAP; EC 2.7.7.19) catalyzes mRNA polyadenylation. Its activity and isoform levels vary during cell cycle transformation and apoptosis. It has become widely accepted that cell death after DNA damage by anticancer agents is primarily the result of apoptosis and that cells able to evade apoptosis will be resistant to cell killing. The therapeutic agents interferon (IFN), 5-fluorouracil (5-FU) and tamoxifen (Tam) with different mechanisms of action mediate both partial dephosphorylation and inactivation of PAP, detected by immunoblotting analysis and PAP enzyme assay, respectively. We examined the apoptotic tendencies of HeLa and WISH cell lines caused by one of the drugs used, 5-FU. The trend in the cells examined, observed by DAPI and/or DNA fragmentation assay, was found to be accompanied by and reversibly related to PAP activity levels and PAP lower mobility phosphorylated forms of 106 and 100 kDa isoforms. Moreover, a cell type-modulated, differential response of HeLa (chemosensitive cells) versus WISH (drug-resistant diploid cells) has been revealed. This finding yields information on the possible use of PAP as a tumor marker involved in cell commitment and/or induction of apoptosis and may help to improve our understanding of tumor cell sensitivity to anticancer agents.

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Biodiversity as a source of new pharmacophores: A new theory of memory III

Pure and Applied Chemistry ◽

10.1351/pac200577010075 ◽

2005 ◽

Vol 77 (1) ◽

pp. 75-81 ◽

Cited By ~ 6

Author(s):

◽

M. Iqbal Choudhary

Keyword(s):

Natural Products ◽

Anticancer Agents ◽

Neurological Disorders ◽

In Vitro Bioassay ◽

Natural Sources ◽

Chemical Basis ◽

Antioxidant Agents ◽

A Cell ◽

The Brain

Several classes of natural products with significant inhibitory activity against target enzymes involved in several diseases have been identified. Spectrophotometer and high-throughput assays were used to assess the inhibition of prolyl endopeptidase (PEP), which led us to some novel inhibitors having potential as anticancer agents. Inhibition of cholinesterase enzymes has led to the discovery of new inhibitors with potential for use in Alzheimer’s disease and other neurological disorders. We have also discovered several potent antioxidant agents from natural sources by using a battery of antioxidant assays. Anti-inflammatory activity of a number of natural products was assayed through a cell-based in vitro bioassay. This article also contains a section on a slightly different topic of chemical basis of memory as presented during the lecture. The theory of the chemical basis of memory based on hydrogen bonding in the brain is further elaborated.

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Use of Yeast Chemigenomics and COXEN Informatics in Preclinical Evaluation of Anticancer Agents

Neoplasia ◽

10.1593/neo.101214 ◽

2011 ◽

Vol 13 (1) ◽

pp. 72-IN19 ◽

Cited By ~ 26

Author(s):

Steven C. Smith ◽

Dmytro M. Havaleshko ◽

Kihyuck Moon ◽

Alexander S. Baras ◽

Jae Lee ◽

...

Keyword(s):

Anticancer Agents ◽

Preclinical Evaluation

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Targeting the Mitotic Catastrophe Signaling Pathway in Cancer

Mediators of Inflammation ◽

10.1155/2015/146282 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 70

Author(s):

Margaret M. Mc Gee

Keyword(s):

Molecular Mechanism ◽

Cell Fate ◽

Anticancer Agents ◽

Therapeutic Benefit ◽

Mitotic Catastrophe ◽

Patient Response ◽

Therapeutic Advantage ◽

Prevention And Treatment ◽

A Cell ◽

Bona Fide

Mitotic catastrophe, as defined in 2012 by the International Nomenclature Committee on Cell Death, is abona fideintrinsic oncosuppressive mechanism that senses mitotic failure and responds by driving a cell to an irreversible antiproliferative fate of death or senescence. Thus, failed mitotic catastrophe can promote the unrestrained growth of defective cells, thereby representing a major gateway to tumour development. Furthermore, the activation of mitotic catastrophe offers significant therapeutic advantage which has been exploited in the action of conventional and targeted anticancer agents. Yet, despite its importance in tumour prevention and treatment, the molecular mechanism of mitotic catastrophe is not well understood. A better understanding of the signals that determine cell fate following failed or defective mitosis will reveal new opportunities to selectively target and enhance the programme for therapeutic benefit and reveal biomarkers to predict patient response. This review is focused on the molecular mechanism of mitotic catastrophe induction and signalling and highlights current strategies to exploit the process in cancer therapy.

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Enhanced antitumor efficacy of telomerase-selective oncolytic adenoviral agent OBP-401 with docetaxel: Preclinical evaluation of chemovirotherapy

International Journal of Cancer ◽

10.1002/ijc.21846 ◽

2006 ◽

Vol 119 (2) ◽

pp. 432-440 ◽

Cited By ~ 56

Author(s):

Toshiya Fujiwara ◽

Shunsuke Kagawa ◽

Hiroyuki Kishimoto ◽

Yoshikatsu Endo ◽

Masayoshi Hioki ◽

...

Keyword(s):

Antitumor Efficacy ◽

Preclinical Evaluation

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Exploratory data analytic techniques to evaluate anticancer agents screened in a cell culture panel

Journal of Biopharmaceutical Statistics ◽

10.1080/10543409208835029 ◽

1992 ◽

Vol 2 (1) ◽

pp. 31-48 ◽

Cited By ~ 13

Author(s):

Louis Hodes ◽

Kenneth Paull ◽

Antonis Koutsoukos ◽

Lawrence Rubinstein

Keyword(s):

Cell Culture ◽

Anticancer Agents ◽

A Cell ◽

Exploratory Data ◽

Data Analytic

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A Cell-Based Radioligand Binding Assay for Farnesyl: Protein Transferase Inhibitors

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057103256153 ◽

2003 ◽

Vol 8 (4) ◽

pp. 430-438 ◽

Cited By ~ 1

Author(s):

Robert B. Lobell ◽

Joseph P. Davide ◽

Nancy E. Kohl ◽

H. Donald Burns ◽

Wai-Si Eng ◽

...

Keyword(s):

Anticancer Agents ◽

Drug Targets ◽

Radioligand Binding ◽

Specific Binding ◽

Intact Cells ◽

C Terminus ◽

A Cell ◽

Ras Oncoprotein ◽

Displacement Assays ◽

In Cells

Farnesyl:protein transferase (FPTase) catalyzes the covalent addition of the isoprenyl moiety of farnesylpyrophosphate to the C-terminus of the Ras oncoprotein and other cellular proteins. Inhibitors of FPTase (FTIs) have been developed as potential anticancer agents, and several compounds have been evaluated in clinical trials. To facilitate the identification of cell-active FTIs with high potency, the authors developed a method that uses a radiolabeled FTI that serves as a ligand in competitive displacement assays. Using high-affinity [3H]-labeled or [125I]-labeled FTI radioligands, they show that specific binding to FPTase can be detected in intact cells. Binding of these labeled FTI radioligands can be competed with a variety of structurally diverse FTIs, and the authors show that inhibition of FTI radioligand binding correlates well with inhibition of FPTase substrate prenylation in cells. This method provides a rapid and quantitative means of assessing FTI potency in cells and is useful for guiding the discovery of potent, novel inhibitors of FPTase. Similar methods could be employed in the optimization of inhibitors for other intracellular drug targets.

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