scholarly journals Xenobiotic response elements (XRE) from human CYP1A1 gene enhance the hTERT promoter activity

2019 ◽  
Vol 485 (5) ◽  
pp. 634-637
Author(s):  
M. V. Shepelev ◽  
S. V. Kalinichenko ◽  
E. K. Saakian ◽  
I. V. Korobko
Keyword(s):  
Transcriptional Activation ◽  
Specific Activity ◽  
Gene Promoter ◽  
Human Lung Cancer ◽  
Htert Promoter ◽  
Cyp1a1 Gene ◽  
Human Lung Cancer Cells ◽  
Hybrid Promoter ◽  
Normal Human ◽  
Xenobiotic Response

A hybrid 6XRE-hTERT promoter consisting of the hTERT tumor-specific promoter and six copies of the XRE element from the CYP1A1 human gene promoter was created. Using a human lung cancer cells as a model, we showed that XRE elements in the hybrid promoter greatly increase the activity of the hTERT promoter and ensure the reporter gene transcriptional activation in response to the treatment of the cells with the AhR ligand benzo(a)pyrene. However, similar effects were also observed in normal human bronchial epithelial cells HBEpC, which indicates the loss of the tumor-specific activity by the 6XRE-hTERT hybrid promoter. XRE elements can be used for nonspecific transcription enhancement but are unsuitable for the creation of tumor-specific promoters with enhanced activity.

A Novel Hybrid Promoter ARE-hTERT for Cancer Gene Therapy

Acta Naturae ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 66-73
Author(s):  
S. V. Kalinichenko ◽  
M. V. Shepelev ◽  
P. N. Vikhreva ◽  
I. V. Korobko
Keyword(s):  
Gene Therapy ◽  
Cancer Cells ◽  
Cytosine Deaminase ◽  
Chimeric Protein ◽  
Gene Promoter ◽  
Cancer Gene Therapy ◽  
Cancer Gene ◽  
Htert Promoter ◽  
Hybrid Promoter

describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the human GCLM gene promoter. The hybrid promoter retains the tumor specificity of the basal hTERT promoter but is characterized by an enhanced transcriptional activity in cancer cells with abnormal activation of the Nrf2 transcription factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein induced a more pronounced death of cancer cells either upon treatment with 5-fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as compared to the hTERT promoter. The developed hybrid promoter can be considered a better alternative to the hTERT promoter in cancer gene therapy schemes.

scholarly journals Cell-specific activity of the modulator region in the human cytomegalovirus major immediate-early gene

1989 ◽  
Vol 9 (3) ◽  
pp. 1342-1345
Author(s):  
H Lubon ◽  
P Ghazal ◽  
L Hennighausen ◽  
C Reynolds-Kohler ◽  
C Lockshin ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Specific Activity ◽  
Gene Promoter ◽  
Early Gene ◽  
Immediate Early ◽  
Upstream Region ◽  
Early Promoter ◽  
Major Immediate Early Promoter

In this paper we demonstrate that modulator sequences upstream of the enhancer of the major immediate-early promoter of human cytomegalovirus exert a differential effect on the level of transcription in a variety of cells and that this region has the capacity to interact with specific nuclear protein. Depending on the cell type, these modulator sequences increased or decreased transcriptional activation from the IE1 gene promoter-enhancer. The cell lines identified in this report should be useful to study the molecular mechanism of cell-specific transcriptional repression and activation exerted by the major immediate-early promoter upstream region.

Xenobiotic Response Elements (XREs) from Human CYP1A1 Gene Enhance the hTERT Promoter Activity

2019 ◽  
Vol 485 (1) ◽  
pp. 150-152
Author(s):  
M. V. Shepelev ◽  
S. V. Kalinichenko ◽  
E. K. Saakian ◽  
I. V. Korobko
Keyword(s):  
Promoter Activity ◽  
Htert Promoter ◽  
Response Elements ◽  
Cyp1a1 Gene ◽  
Xenobiotic Response

scholarly journals Cell-specific activity of the modulator region in the human cytomegalovirus major immediate-early gene.

1989 ◽  
Vol 9 (3) ◽  
pp. 1342-1345 ◽  
Author(s):  
H Lubon ◽  
P Ghazal ◽  
L Hennighausen ◽  
C Reynolds-Kohler ◽  
C Lockshin ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Transcriptional Activation ◽  
Transcriptional Repression ◽  
Specific Activity ◽  
Gene Promoter ◽  
Early Gene ◽  
Immediate Early ◽  
Upstream Region ◽  
Early Promoter ◽  
Major Immediate Early Promoter

In this paper we demonstrate that modulator sequences upstream of the enhancer of the major immediate-early promoter of human cytomegalovirus exert a differential effect on the level of transcription in a variety of cells and that this region has the capacity to interact with specific nuclear protein. Depending on the cell type, these modulator sequences increased or decreased transcriptional activation from the IE1 gene promoter-enhancer. The cell lines identified in this report should be useful to study the molecular mechanism of cell-specific transcriptional repression and activation exerted by the major immediate-early promoter upstream region.

scholarly journals Targeted Gold Nanohybrids Functionalized with Folate-Hydrophobic-Quaternized Pullulan Delivering Camptothecin for Enhancing Hydrophobic Anticancer Drug Efficacy

Polymers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 2670
Author(s):  
Sakchai Laksee ◽  
Chamaiporn Supachettapun ◽  
Nongnuj Muangsin ◽  
Pattra Lertsarawut ◽  
Thitirat Rattanawongwiboon ◽  
...  
Keyword(s):  
Human Lung ◽  
Folate Receptor ◽  
Drug Efficacy ◽  
New Combination ◽  
Human Lung Cancer ◽  
Apoptosis Pathway ◽  
Human Lung Cells ◽  
Human Lung Cancer Cells ◽  
Normal Human ◽  
Average Size

This study presented a green, facile and efficient approach for a new combination of targeted gold nanohybrids functionalized with folate-hydrophobic-quaternized pullulan delivering hydrophobic camptothecin (CPT-GNHs@FHQ-PUL) to enhance the efficacy, selectivity, and safety of these systems. New formulations of spherical CPT-GNHs@FHQ-PUL obtained by bio-inspired strategy were fully characterized by TEM, EDS, DLS, zeta-potential, UV-vis, XRD, and ATR-FTIR analyses, showing a homogeneous particles size with an average size of approximately 10.97 ± 2.29 nm. CPT was successfully loaded on multifunctional GNHs@FHQ-PUL via intermolecular interactions. Moreover, pH-responsive CPT release from newly formulated-CPT-GNHs@FHQ-PUL exhibited a faster release rate under acidic conditions. The intelligent CPT-GNHs@FHQ-PUL (IC50 = 6.2 μM) displayed a 2.82-time higher cytotoxicity against human lung cancer cells (Chago-k1) than CPT alone (IC50 = 2.2 μM), while simultaneously exhibiting less toxicity toward normal human lung cells (Wi-38). These systems also showed specific uptake by folate receptor-mediated endocytosis, exhibited excellent anticancer activity, induced the death of cells by increasing apoptosis pathway (13.97%), and arrested the cell cycle at the G0-G1 phase. The results of this study showed that the delivery of CPT by smart GNHs@FHQ-PUL systems proved to be a promising strategy for increasing its chemotherapeutic effects.

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