Real-time Detection of Gene Expression in Cancer Cells Using Molecular Beacon Imaging: New Strategies for Cancer Research

Peng, Xianghong; Cao, Zehong; Xia, Jianguo; Carlson, Grant W.; Lewis, Melinda M.; Wood, William C.; Yang, Lily

doi:10.1158/0008-5472.can-04-3196

Cited by 163 publications

(120 citation statements)

References 23 publications

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“…The ability of deguelin to block both survivin and XIAP expression provides a great opportunity for sensitizing human cancer cells to chemotherapy. Previous studies, including ours, revealed that treatment of human cancer cells with many of the drugs used in chemotherapy today induced up-regulation of survivin expression (Ikeguchi et al, 2002;Ling et al, 2004;Peng et al, 2005, Ling, 2004. However, the undesirable effect of increasing the level of survivin has been shown to prevent the downstream apoptotic response and decrease drug sensitivity (Tamm et al, 1998).…”

Section: Deguelin Treatment Counteracts Chemotherapy Drug-induced Up-mentioning

confidence: 82%

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Down-Regulation of Inhibitor of Apoptosis Proteins by Deguelin Selectively Induces Apoptosis in Breast Cancer Cells

Peng

Karna²,

O’Regan³

et al. 2007

Molecular Pharmacology

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The identification of differentially regulated apoptotic signals in normal and tumor cells allows the development of cancer cellselective therapies. Increasing evidence shows that the inhibitor of apoptosis (IAP) proteins survivin and XIAP are highly expressed in tumor cells but are absent or have very low levels of expression in normal adult tissues. We found that inhibiting AKT activity with 10 to 100 nM deguelin, a small molecule derived from natural products, markedly reduced the levels of both survivin and XIAP, inducing apoptosis in human breast cancer cells but not in normal cells. It is noteworthy that we detected an elevated level of cleaved poly(ADP-ribose) polymerase, a signature of caspase activation, without a significant increase in caspase activity in deguelin-treated cancer cells. Our results suggest that severe down-regulation of the IAPs by deguelin releases their inhibitory activity over pre-existing active caspases present in cancer cells, inducing apoptosis without the need for further caspase activation. Because normal cells have very low levels of p-AKT, XIAP, survivin, and preexisting caspase activity, deguelin had little effect on those cells. In addition, we found that combining deguelin with chemotherapy drugs enhanced drug-induced apoptosis selectively in human tumor cells, which suggests that deguelin has great potential for chemosensitization and could represent a new therapeutic agent for treatment of breast cancer.The development of mechanisms that give resistance to apoptosis confers both a high survival ability and a low drug sensitivity to human cancer cells (Deveraux and Reed, 1999;Reed, 1999). To develop cancer-specific therapeutic approaches, it is important to identify the molecular targets in the apoptotic pathway that are differentially regulated in normal and tumor cells. It is well known that a balance of pro-and anti-apoptotic factors determines whether a cell survives or undergoes apoptosis (Igney and Krammer, 2002;Yang et al., 2003). In tumor cells, apoptosis can be induced either by activation of molecules upstream of apoptosis signaling or by inhibition of antiapoptotic factors (Mesri et al., 2001;Reed, 2001). A previous study of ours shows that although direct activation of caspase 3 is able to induce apoptosis, normal cells still seem to be more sensitive to caspase 3-induced activation of apoptosis than human tumor cells are (Yang et al., 2003). The presence in cancer cells, but not normal cells, of high levels of antiapoptotic factors, such as the inhibitor of apoptosis (IAP) proteins may confer this insensitivity to apoptosis induction by caspase 3 activation in tumor cells. Members of the IAP family of proteins contain one or more conserved regions termed baculoviral IAP repeat (BIR) N-terminal domains and a C-terminal RING domain (Deveraux and Reed, 1999;Reed, 1999). The BIR domain of these IAP binds to active caspases to block their activity, whereas the RING domain acts as an ubiquitin ligase to facilitate proteasomal degradation of caspases (Listo...

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Section: Deguelin Treatment Counteracts Chemotherapy Drug-induced Up-mentioning

confidence: 82%

“…We and others have observed that human cancer cells further up-regulate survivin expression after chemotherapy drug treatment (Ikeguchi et al, 2002;Ling et al, 2004;Peng et al, 2005). These increases may prevent the downstream apoptotic response and decrease (to varying degrees) the sensitivity of the cells to these agents.…”

Section: Downloaded Frommentioning

confidence: 88%

Down-Regulation of Inhibitor of Apoptosis Proteins by Deguelin Selectively Induces Apoptosis in Breast Cancer Cells

Peng

Karna²,

O’Regan³

et al. 2007

Molecular Pharmacology

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“…Using nanotechnology the determination of survivin will be easier and its use in cancer research and cancer treatment will meet the requirements for real time [12]. The oligonucleotide molecular beacons encoded for survivin mRNA have been proposed for the indirect detection of survivin expression [15]. Despite such advancements, a broad application of biomarkers in clinical practice is hampered by lack of specificity and generalizability to the population.…”

Section: Clinical Utility Of Biomarkers In Cancermentioning

confidence: 99%

Some aspects of cancer biomarkers and their clinical application in solid tumors – revisited

Isaac¹,

Elayoubi²,

A³

et al. 2017

J Cancer Res Ther.

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Cancer biomarkers can be used for a variety of purposes related to screening, prediction, stratification, detection, diagnosis, prognosis, treatment design, and monitoring of a therapeutic response. One of the most important characteristics of a given biomarker includes ease of collection allowing for a non-invasive approach and frequent sampling. Such samples may be obtained from serum or plasma, sputum, bronchoalveolar lavage, saliva, nipple discharge, pleural, or peritoneal effusions. Validation of different biomarkers is considered a mandatory method for useful evaluation. In this review, we highlight the clinical applicability of some cancer biomarkers, as well as future approaches for their development and collection, which may help guide clinicians and researchers. The role of liquid biopsies will also be summarized. Further studies using liquid biopsies are needed to elucidate the significance of various sources of biomarkers suitable for clinical application.

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“…This important attribute could potentially be taken advantage of to highlight the orchestration between various gene expression patterns in living cells. In fact, several groups have already demonstrated the feasibility of simultaneously imaging multiple genes in single living cells with molecular beacons [69,70]. To further reduce background signal, especially that due to degradation of beacons by endonucleases in living cells, a novel dual FRET-molecular beacons approach was developed; it utilizes a pair of molecular beacons each labeled with a donor and acceptor fluorophore as illustrated in Figure 3B [65,66].…”

Section: Molecular Beaconsmentioning

confidence: 99%

Engineering imaging probes and molecular machines for nanomedicine

Tong

Cradick

et al. 2012

Sci. China Life Sci.

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Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, life sciences and medicine; it is expected to produce major breakthroughs in medical diagnostics and therapeutics. Due to the size-compatibility of nano-scale structures and devices with proteins and nucleic acids, the design, synthesis and application of nanoprobes, nanocarriers and nanomachines provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention. Recent advances in nanomedicine include the development of functional nanoparticle based molecular imaging probes, nano-structured materials as drug/gene carriers for in vivo delivery, and engineered molecular machines for treating single-gene disorders. This review focuses on the development of molecular imaging probes and engineered nucleases for nanomedicine, including quantum dot bioconjugates, quantum dot-fluorescent protein FRET probes, molecular beacons, magnetic and gold nanoparticle based imaging contrast agents, and the design and validation of zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) for gene targeting. The challenges in translating nanomedicine approaches to clinical applications are discussed. Nanomedicine is an emerging field that integrates nanotechnology, biomolecular engineering, biology, and medicine [1]. It focuses on the development of engineered nano-scale (1100 nm) materials, structures and devices for better diagnostics and highly specific medical intervention in curing disease or repairing damaged tissues. As a basis for nanomedicine, nanotechnology is the science, engineering, and technology related to the understanding and control of matter at the nano-scale, and the development of materials, devices, and systems that have novel properties and functions due to their nano-scale dimensions or components. Nanotechnology also provides new abilities to measure, control and manipulate matter (including soft matter) at the nano-scale what was unthinkable with conventional tools. Owing to the size-compatibility of nano-scale structures with proteins and nucleic acids in living cells, nanomedicine approaches have the potential to provide unprecedented opportunities for achieving a better control of biological processes, and drastic improvements in disease detection, therapy, and prevention, thus revolutionizing medicine. Over the last ten years or so, significant efforts have been made in the US, China, Europe and elsewhere to develop nanomedicine. For example, the US National Institutes of Health has developed a nanomedicine centers network, and invested a significant amount of research funding to nanomedicine development. Just in FY 2009 (Oct. 1, 2008Sept. 30, 2009, the total NIH funding in nanotechnology/ nanoscience projects was more than 410 million US dollars. SPECIAL TOPIC

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Real-time Detection of Gene Expression in Cancer Cells Using Molecular Beacon Imaging: New Strategies for Cancer Research

Cited by 163 publications

References 23 publications

Down-Regulation of Inhibitor of Apoptosis Proteins by Deguelin Selectively Induces Apoptosis in Breast Cancer Cells

Down-Regulation of Inhibitor of Apoptosis Proteins by Deguelin Selectively Induces Apoptosis in Breast Cancer Cells

Some aspects of cancer biomarkers and their clinical application in solid tumors – revisited

Engineering imaging probes and molecular machines for nanomedicine

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