Regulation of MDK expression in human cancer cells modulates sensitivities to various anticancer drugs: MDK overexpression confers to a multi-drug resistance

Kang, Hio Chung; Kim, Il-Jin; Park, Hyewon; Jang, Sang-Geun; Ahn, Se Jin; Yoon, Sang Nam; Chang, Hee-Jin; Yoo, Byong Chul; Park, Jae-Gahb

doi:10.1016/j.canlet.2006.03.017

Cited by 45 publications

(35 citation statements)

References 20 publications

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“…It is a heparin-binding growth factor involved in cancer development, the promotion of cell growth and survival, angiogenesis and anti-apoptosis (35). Notably, over-expression of MDK has been demonstrated to be associated with resistance to different chemotherapeutic agents, including fluorouracil, doxorubicin, cisplatin and adriamycin (36,37). Therefore, acquired upregulation of MDK in CML cells may contribute to cyclophosphamide resistance.…”

Section: Discussionmentioning

confidence: 99%

Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia

Xiao

Deng

Yue

2017

Molecular Medicine Reports

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Drug resistance is an obstacle in the treatment of chronic myelogenous leukemia (CML), and is a common reason for treatment failure or disease progression. However, the underlying mechanisms of cyclophosphamide resistance remain poorly defined. In the present study, microarray data concerning cyclophosphamide-sensitive and -resistant chronic myelogenous leukemia cell lines were analyzed. A total of 258 differentially-expressed genes (DEGs) were identified between these two groups, from which 139 DEGs were upregulated and 119 were downregulated. Several candidate genes that were associated with cyclophosphamide resistance were also identified. These DEGs were subsequently classified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis. A total of 487 biological processes and 17 KEGG pathways were revealed to be enriched. Furthermore, an interaction network was established to identify the core genes that regulated cyclophosphamide resistance. Signal transducer and activator of transcription 5A (STAT5A), FYN proto-oncogene, Src family tyrosine kinase and spleen associated tyrosine kinase were revealed to be the hub genes in multiple enriched biological processes and signaling pathways, indicating that these were involved in mediating cyclophosphamide sensitivity in CML cells. The expression levels of 5 DEGs were also confirmed in two human CML cell lines (K-562 and KU812) by reverse transcription-quantitative polymerase chain reaction. Furthermore, selective knockdown of STAT5A and S100 calcium binding protein A4 (S100A4) recovered cyclophosphamide sensitivity in K-562 cells, suggesting their involvement in drug resistance. The present study identified several potential genes and pathways contributing to cyclophosphamide resistance, and confirmed the involvement of STAT5A and S100A4 in drug resistance. These results enable improved understanding of the mechanisms underlying drug resistance in CML cells.

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Section: Discussionmentioning

confidence: 99%

Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia

Xiao

Deng

Yue

2017

Molecular Medicine Reports

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“…[43] The anticancer drug cisplatin did not show any PDT effect and its IC 50 value is significantly higher than that of Photofrin ® in red light for HeLa cells. [44] Figure 7. Cytotoxicity of compound 1 in human cervical HeLa cancer cells upon incubation for 4 h in the dark followed by irradiation by visible light (400 to 700 nm) as determined by MTT assay.…”

Section: Photocytotoxicity Studymentioning

confidence: 98%

DNA Photocleavage and Cytotoxic Properties of Ferrocene Conjugates

et al. 2011

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“…Complex 4 gave lower IC 50 value than cisplatin (IC 50 = 70 μm) and showed similar PDT effect as is known for Photofrin ® (IC 50 = 2.57 μm) ( Table 2). [66,67] The photocytotoxic property of complex 4 makes it a potential candidate for further study to augment its PDT activity. The effectiveness of 2 and 4 towards showing reduced cell viability was assessed from the statistical analysis.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Terpyridine Oxovanadium(IV) Complexes of Phenanthroline Bases for Cellular Imaging and Photocytotoxicity in HeLa Cells

et al. 2011

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Oxovanadium(IV) complexes [VO(N‐N‐N)(N‐N)](NO3)2 (1–4) of (4′‐phenyl)‐2,2′:6′,2″‐terpyridine (ph‐tpy in 1 and 2) or (4′‐pyrenyl)‐2,2′:6′,2″‐terpyridine (py‐tpy in 3 and 4) having N‐N as 1,10‐phenanthroline (phen in 1 and 3) or dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz in 2 and 4) are prepared and characterized. The crystal structure of 1 has VO2+ group in VN5O coordination geometry. The terpyridine ligand coordinates in a meridional binding mode. The phen ligand displays a chelating mode of binding with an N‐donor site trans to the vanadyl oxo group. The complexes show a d‐d band in the range of 710–770 nm in aqueous DMF (4:1 v/v). The complexes exhibit an irreversible VIV/VIII redox response near –1.0 V vs. SCE in aqueous DMF/0.1 M KCl. The complexes bind to CT DNA giving Kb values within 3.5 × 105 to 1.2 × 106 M–1. The complexes show poor chemical nuclease activity in dark. Complexes 2–4 show photonuclease activity in UV‐A light of 365 nm forming 1O2 and ·OH. Complex 4 shows DNA photocleavage activity at near‐IR light of 785 nm forming ·OH radicals. Complexes 2 and 4 show significant photocytotoxicity in HeLa cancer cells. Uptake of the complexes in HeLa cells, studied by fluorescence imaging, show predominantly cytosolic localization inside the cells.

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Regulation of MDK expression in human cancer cells modulates sensitivities to various anticancer drugs: MDK overexpression confers to a multi-drug resistance

Cited by 45 publications

References 20 publications

Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia

Investigating critical genes and gene interaction networks that mediate cyclophosphamide sensitivity in chronic myelogenous leukemia

DNA Photocleavage and Cytotoxic Properties of Ferrocene Conjugates

Terpyridine Oxovanadium(IV) Complexes of Phenanthroline Bases for Cellular Imaging and Photocytotoxicity in HeLa Cells

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