c-Abl-independent p73 stabilization during gemcitabine- or 4′-thio-β-<scp>d</scp>-arabinofuranosylcytosine–induced apoptosis in wild-type and p53-null colorectal cancer cells

Thottassery, Jaideep V.; Westbrook, Louise; Someya, Hitoshi; Parker, William B.

doi:10.1158/1535-7163.mct-05-0409

Cited by 22 publications

(14 citation statements)

References 57 publications

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“…These results support the use of TaraC over araC because at clinically achievable drug concentrations its accumulation in tumors is sustained (Parker et al, 2000) and independent of the drug administration schedule (Waud et al, 2003). In addition, recent studies (Thottassery et al, 2006) have shown that TaraC, but not araC, is a potent inducer of apoptosis by stabilization of p73 in both p53-positive and p53-negative cells, providing evidence favoring use of TaraC in treatment of tumors.…”

Section: Discussionmentioning

confidence: 99%

The Role of Human Nucleoside Transporters in Cellular Uptake of 4′-Thio-β-d-arabinofuranosylcytosine and β-d-Arabinosylcytosine

Clarke¹,

Damaraju²,

Zhang³

et al. 2006

Mol Pharmacol

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combinant transporters (produced in yeast) for a panel of cytosine-containing nucleosides yielded results that were consistent with the observed low-permeant activities of TaraC and araC for hENT1/2 and negligible permeant activities for hCNT1/ 2/3. During prolonged drug exposures of CEM cells with hENT1 activity, araC was more cytotoxic than TaraC, whereas coexposures with nitrobenzylthioinosine (to pharmacologically block hENT1) yielded identical cytotoxicities for araC and TaraC. The introduction by gene transfer of hENT2 and hCNT1 activities, respectively, into nucleoside transport-defective CEM cells increased sensitivity to both drugs moderately and slightly. These results demonstrated that nucleoside transport capacity (primarily via hENT1, to a lesser extent by hENT2 and possibly by hCNT1) is a determinant of pharmacological activity of both drugs.

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Section: Discussionmentioning

confidence: 99%

The Role of Human Nucleoside Transporters in Cellular Uptake of 4′-Thio-β-d-arabinofuranosylcytosine and β-d-Arabinosylcytosine

Clarke¹,

Damaraju²,

Zhang³

et al. 2006

Mol Pharmacol

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“…We also reported that AURKA over-expression suppresses TAp73 in p53 deficient cancer cells (37). TAp73, a p53 family, member has significant homology with p53 and plays an essential role in apoptosis induced by cytotoxic agents (38). The tumor suppressor proteins p53 and p73 can activate genetic programs that halt cell proliferation transiently (G1 and G2 cell cycle arrest) or permanently (senescence) or eliminate the cell altogether (apoptosis).…”

Section: Aurka's Role In Tumor Developmentmentioning

confidence: 99%

Aurora Kinase Inhibitors - Rising Stars in Cancer Therapeutics?

Dar

Goff

Majid

et al. 2010

Molecular Cancer Therapeutics

225

220

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Standard therapeutic approaches of cytotoxics and radiation in cancer are not only highly toxic, but also of limited efficacy in treatment of a significant number of cancer patients. The molecular analysis of the cancer genomes have shown a remarkable complexity and pointed to key genomic and epigenomic alterations in cancer. These discoveries are paving the way for targeted therapy approaches. However, although there are a large number of potential targets, only a few can regulate key cellular functions and intersect multiple signaling networks. The Aurora kinase family members (A, B, and C) are a collection of highly related and conserved serine-threonine kinases that fulfill these criteria, being key regulators of mitosis and multiple signaling pathways. Alterations in Aurora kinase signaling are associated with mitotic errors and have been closely linked to chromosomal aneuploidy in cancer cells. Several studies have shown amplification and/or overexpression of Aurora kinase A and B in hematologic malignancies and solid tumors. Over the past several years, Aurora kinases have become attractive targets. Several ongoing clinical trials and bench-based research are assessing the unique therapeutic potential of Aurora-based targeted therapy.Mol Cancer Ther; 9(2); 268-78. ©2010 AACR.

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“…Similar to p53, activated p73 mediates a cellular response to radio- and chemotherapy, including γ-irradiation and treatment with cisplatin, doxorubicin, camptothecin, etoposide, bleomycin, mitoxantrone, taxol, and the cytosine analogues gemcitabine, Ara-C and T-ara-C (Agami et al, 1999; Costanzo et al, 2002; Gong et al, 1999; Lin et al, 2004; Müller et al, 2005; Müller et al, 2006; Thottassery et al, 2006; Vayssade et al, 2005; Yuan et al, 1999). TAp73 is regulated on both transcriptional and post-translational levels following cellular stress.…”

Section: P73 and P63 In Anti-cancer Therapymentioning

confidence: 99%

Therapeutic prospects for p73 and p63: Rising from the shadow of p53

Vilgelm

El–Rifai

Zaika

2008

Drug Resistance Updates

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The p53 protein family consists of three transcription factors: p53, p63, and p73. These proteins share significant structural and functional similarities and each has unique biological functions as well. Although the role of p53 in cellular stress is extensively studied, many questions remain about p63 and p73. In this review we summarize current data on functional interactions within the p53 family, their regulation and roles in response to genotoxic stress. We also discuss significance of p73 and p63 for cancer therapy and outline novel approaches in development of therapeutic drugs that specifically target the p53 family.

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c-Abl-independent p73 stabilization during gemcitabine- or 4′-thio-β-d-arabinofuranosylcytosine–induced apoptosis in wild-type and p53-null colorectal cancer cells

Abstract: Nucleoside anticancer drugs like gemcitabine (2V -deoxy-2V

Cited by 22 publications

References 57 publications

The Role of Human Nucleoside Transporters in Cellular Uptake of 4′-Thio-β-d-arabinofuranosylcytosine and β-d-Arabinosylcytosine

The Role of Human Nucleoside Transporters in Cellular Uptake of 4′-Thio-β-d-arabinofuranosylcytosine and β-d-Arabinosylcytosine

Aurora Kinase Inhibitors - Rising Stars in Cancer Therapeutics?

Therapeutic prospects for p73 and p63: Rising from the shadow of p53

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