Erkitinib, a novel EGFR tyrosine kinase inhibitor screened using a ProteoChip system from a phytochemical library

Kim, Eung-Yoon; Choi, Youngjin; Park, Chan-Won; Kang, In‐Cheol

doi:10.1016/j.bbrc.2009.08.141

Cited by 9 publications

(4 citation statements)

References 19 publications

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“…EGFR tyrosine kinase inhibition has been previously described to block proliferation 30 and induce toxicity 31 in HeLa cells. To characterize the effects of EGFR tyrosine kinase inhibition using erlotinib, we treated HeLa cells with increasing concentrations of this molecule.…”

Section: Resultsmentioning

confidence: 99%

Autophagy inhibition cooperates with erlotinib to induce glioblastoma cell death

Eimer¹,

Belaud‐Rotureau²,

Airiau³

et al. 2011

Cancer Biology & Therapy

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Gliomas are the most common malignant primary brain tumors in adults. The median survival never exceeds 12 months, owing to inherent resistance to both radio and chemotherapies. Epidermal Growth Factor Receptor (EGFR) is amplified, overexpressed, and/or mutated in glioblastomas (GBM), making it a rational for therapy. Erlotinib, an EGFR kinase inhibitor is strongly associated with clinical response in several cancers. Inhibition of cell proliferation and induction of apoptosis by erlotinib were investigated in U87-MG and DBTRG-05MG, two human glioblastoma cell lines. The expression of several apoptosis-related proteins was investigated in these cell lines and in tumoral tissue from glioblastomas. Both cell lines expressed wild-type EGFR but were deficient for PTEN. Erlotinib induced a marked accumulation of the BIM protein, but the activation of caspase-3 machinery was missing, regardless of the decrease in XIAP. Moreover, in U87-MG, erlotinib promoted accumulation of αB-crystallin a small heat shock protein capable to impair caspase activation. DBTRG-05MG was found deficient for procaspase 3 and constitutively overexpressed αB-crystallin. Similarly, deficiencies in PTEN and procaspase 3 were constantly found in samples from glioblastoma samples, while αB-crystallin expression was inconsistent. In cell lines, high concentrations of erlotinib induced cell death through a caspase independent process and an autophagic process was evidenced in U87-MG. Inhibition of autophagy induced a marked increase in the death-inducing activity of erlotinib. These results confirm that glioblastoma cell lines exhibit several anti-apoptotic mechanisms, and underline that EGFR targeted therapy must be associated to other inhibitors to achieve an antitumoral effect.

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Section: Resultsmentioning

confidence: 99%

Autophagy inhibition cooperates with erlotinib to induce glioblastoma cell death

Eimer¹,

Belaud‐Rotureau²,

Airiau³

et al. 2011

Cancer Biology & Therapy

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“…Phytochemical binds to the PfRIO-2 kinase with specificity Phytochemicals are natural products with proven therapeutic potentials against leishmania, fungal diseases, malaria and cancer [19,20]. Isolation of phytochemicals for drug development depends on the abundance of phytochemicals as well as their distribution in plant species.…”

Section: Resultsmentioning

confidence: 99%

Identification and screening of antimalarial phytochemical reservoir from northeastern Indian plants to develop PfRIO-2 kinase inhibitor

Nag

Prasad

Trivedi

2012

Eur Food Res Technol

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Every year, malaria caused by Plasmodium falciparum leads to 1 million deaths. Disease condition is alarming due to acquired resistance in parasite against antimalarial drugs in circulation. It brings the necessity to design novel inhibitors against newly identified drug targets. RIO-2 kinase regulates ribosome biogenesis and represents a promising drug target. Northeastern region of India is a biodiversity hub with a rich source of medicinal plants. Medicinal plants represent a source of phytochemical library to be screened to develop an inhibitor against the PfRIO-2 kinase. In current report, we selected plants with known antimalarial activity and performed in silico screening with phytochemicals against PfRIO-2 as a target. The majority of antimalarial phytochemicals docked very well into the ATP binding pocket of the PfRIO-2 kinase. A competition assay with substrate ATP indicates that a total of 5 phytochemicals, rutin, bebeerines, isochondrodendrine, nimbin and punicalagin, share similar interactions with protein residues within the ATP binding pocket and have potential to inhibit ATP binding. A significant relationship was found between docking energy and experimentally determined antimalarial values of rutin, bebeerines, isochondrodendrine, nimbin and punicalagin (R 2 = 0.91, p \ 0.001). Docking and virtual screening has identified lead phytochemicals, namely rutin, bebeerines, isochondrodendrine, nimbin and punicalagin, as a potent PfRIO-2 inhibitor, but cannot replace experimental verification. We are hopeful that the current study will help to understand the antimalarial action of the phytochemicals and design effective chemotherapy against malaria.

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“…Among the reasons, minute sample quantities coupled with the analytical detection limits have thwarted the efforts to identify which signaling pathways, as well as which genes or protein components are being targeted by these bioactive phytochemicals. The recent advances in proteomic techniques (MALDI TOF-TOF, proteoChip, capillary gel electrophoresis) have overcome some of these challenges and eased the target identifications in these phytochemical-mediated actions (Kim et al, 2009;Lu et al, 2011). Through the combinatorial applications of comparative proteomic and other biotechnology techniques, researchers are able to investigate the cellular protein expression profiles, upon exposure to phytochemicals (Figure 1).…”

Section: Scope Of Reviewmentioning

confidence: 98%

Phytochemical-mediated Protein Expression Profiling and the Potential Applications in Therapeutic Drug Target Identifications

Wong

Tan

Chai

2015

Critical Reviews in Food Science and Nutrition

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Many phytochemicals derived from edible medicinal plants have been investigated intensively for their various bioactivities. However, the detailed mechanism and their corresponding molecular targets frequently remain elusive. In this review, we present a summary of the research works done on phytochemical-mediated molecular targets, identified via proteomic approach. Concurrently, we also highlighted some pharmaceutical drugs which could be traced back to their origins in phytochemicals. For ease of presentation, these identified protein targets were categorized into two important healthcare-related fields, namely anti-bacterial and anti-cancer research. Through this review, we hope to highlight the usefulness of comparative proteomic as a powerful tool in phytochemical-mediated protein target identifications. Likewise, we wish to inspire further investigations on some of these protein targets identified over the last few years. With contributions from all researchers, the accumulative efforts could eventually lead to the discovery of some target-specific, low-toxicity therapeutic agents.

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Erkitinib, a novel EGFR tyrosine kinase inhibitor screened using a ProteoChip system from a phytochemical library

Cited by 9 publications

References 19 publications

Autophagy inhibition cooperates with erlotinib to induce glioblastoma cell death

Autophagy inhibition cooperates with erlotinib to induce glioblastoma cell death

Identification and screening of antimalarial phytochemical reservoir from northeastern Indian plants to develop PfRIO-2 kinase inhibitor

Phytochemical-mediated Protein Expression Profiling and the Potential Applications in Therapeutic Drug Target Identifications

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