Synthesis of Quinoline Motif and Their Virtual HIV Protease Inhibition Analysis, Anti‐Proliferative Probing on HCT116 Cell Line

2019 ◽  
Vol 4 (25) ◽  
pp. 7627-7633
Author(s):  
P. Gopi ◽  
R. Lokesh ◽  
S. Sarveswari
1998 ◽  
Vol 18 (1) ◽  
pp. 303-313 ◽  
Author(s):  
Gillian M. Howell ◽  
Lisa E. Humphrey ◽  
Barry L. Ziober ◽  
Rana Awwad ◽  
Basker Periyasamy ◽  
...  

ABSTRACT Aberrant transcriptional regulation of transforming growth factor α (TGFα) appears to be an important contributor to the malignant phenotype and the growth factor independence with which malignancy is frequently associated. However, little is known about the molecular mechanisms responsible for dysregulation of TGFα expression in the malignant phenotype. In this paper, we report on TGFα promoter regulation in the highly malignant growth factor-independent cell line HCT116. The HCT116 cell line expresses TGFα and the epidermal growth factor receptor (EGFR) but is not growth inhibited by antibodies to EGFR or TGFα. However, constitutive expression of TGFα antisense RNA in the HCT116 cell line resulted in the isolation of clones with markedly reduced TGFα mRNA and which were dependent on exogenous growth factors for proliferation. We hypothesized that if TGFα autocrine activation is the major stimulator of TGFα expression in this cell line, TGFα promoter activity should be reduced in the antisense TGFα clones in the absence of exogenous growth factor. This was the case. Moreover, transcriptional activation of the TGFα promoter was restored in an antisense-TGFα-mRNA-expressing clone which had reverted to a growth factor-independent phenotype. Using this model system, we were able to identify a 25-bp element within the TGFα promoter which conferred TGFα autoregulation to the TGFα promoter in the HCT116 cell line. In the TGFα-antisense-RNA-expressing clones, this element was activated by exogenous EGF. This 25-bp sequence contained no consensus sequences of known transcription factors so that the TGFα or EGF regulatory element within this 25-bp sequence represents a unique element. Further characterization of this 25-bp DNA sequence by deletion analysis revealed that regulation of TGFα promoter activity by this sequence is complex, as both repressors and activators bind in this region, but the overall expression of the activators is pivotal in determining the level of response to EGF or TGFα stimulation. The specific nuclear proteins binding to this region are also regulated in an autocrine-TGFα-dependent fashion and by exogenous EGF in EGF-deprived TGFα antisense clone 33. This regulation is identical to that seen in the growth factor-dependent cell line FET, which requires exogenous EGF for optimal growth. Moreover, the time response of the stimulation oftrans-acting factor binding by EGF suggests that the effect is directly due to growth factor and not mediated by changes in growth state. We conclude that this element appears to represent the major positive regulator of TGFα expression in the growth factor-independent HCT116 cell line and may represent the major site of transcriptional dysregulation of TGFα promoter activity in the growth factor-independent phenotype.


2017 ◽  
Vol 29 (1) ◽  
Author(s):  
Eman Althubaiti ◽  
Abdulkader Shaikh Omar ◽  
Mohammed Almatry ◽  
Yasir Anwar ◽  
Soufyan ElAssouli

2017 ◽  
Vol 61 (1) ◽  
pp. 1400340 ◽  
Author(s):  
Yangping Ding ◽  
Bingcan Chen ◽  
Zili Gao ◽  
Huayi Suo ◽  
Hang Xiao

2019 ◽  
Vol 35 (1) ◽  
pp. 471-475
Author(s):  
Aryo Tedjo ◽  
Fadilah Fadilah ◽  
Kusmardi Kusmardi ◽  
Rafika Indah Paramita ◽  
Fadhilah Harmen ◽  
...  

2020 ◽  
Vol 29 (3) ◽  
pp. 361-367
Author(s):  
Sergiu Pasca ◽  
Calin Ionescu ◽  
David Andras ◽  
Dan Eniu ◽  
Mihai Andrei Muresan ◽  
...  

Background and Aims: Although colon cancer has a decreasing incidence trend in Europe, because of its still high frequency and not fully understood pathogenesis, this malignancy still remains a subject of intense research. The aim of this study was to investigate the role of microRNA-194 and microRNA-1228 in colon cancer proliferation. Methods: RNA was extracted from patients with colon cancer with or without advanced disease and microRNA expression levels were determined through qRT-PCR. Assays were performed on HCT116 cell line and included qRT-PCR, western blotting and cell counting. Results: We observed that both microRNAs 194 and 1228 were altered in patients with colon cancer compared with healthy individuals. We observed a lower expression of both microRNA-194 and microRNA-1228 in patients with advanced colon cancer. To validate their pathogenetic role we performed viability and invasion assays on HCT116 cell line transfected with mimics or inhibitors of the mentioned microRNAs, with observable changes in viability and invasion. Furthermore, to determine the altered signaling induced by these microRNAs, we performed western blotting for phospho S6 on HCT116 cells transfected with mimic and inhibitor of the above-mentioned microRNAs with observable differences. Conclusion: In the current study we have shown that both microRNA-194 and microRNA-1228 alteration was correlated with the presence of advanced colon cancer, a fact that was further validated in vitro through an invasion assay. Moreover, we have also shown that their effect might be mediated through phospho S6 expression.


Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 343 ◽  
Author(s):  
Orlando ◽  
Ferrante ◽  
Zengin ◽  
Sinan ◽  
Bene ◽  
...  

Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae) has a long history of use by folk populations for the management of multiple human ailments. Based on the published literature, there has been no attempt to conduct a comparative assessment of the biological activity and the phytochemical profiles of the leaves and stem bark of A. leiocarpus extracted using methanol, ethyl acetate, and water. By high-performance liquid chromatography with electrospray ionization mass spectrometric detection (HPLC-ESI-MSn) analysis, quinic, shikimic, gallic, and protocatechuic acids were tentatively identified from all the extracts, while chlorogenic, caffeic, ferulic, and dodecanedioic acids were only characterised from the leaves extracts. Additionally, a pharmacological study was carried out to evaluate potential protective effects that are induced by the extracts in rat colon and colon cancer HCT116 cell line. In general, the methanol and water extracts of A. leiocarpus leaves and stem bark showed potent radical scavenging and reducing properties. It was noted that the stem bark extracts were more potent antioxidants as compared to the leaves extracts. The methanol extract of A. leiocarpus leaves showed the highest acetyl (4.68 mg galantamine equivalent/g) and butyryl (4.0 mg galantamine equivalent/g) cholinesterase inhibition. Among ethyl acetate extracts, the pharmacological investigation suggested stem bark ethyl acetate extracts to be the most promising. This extract revealed ability to protect rat colon from lipopolysaccharide-induced oxidative stress, without exerting promoting effects on HCT116 cell line viability and migration. As a conclusion, A. leiocarpus represents a potential source of bioactive compounds in the development of novel therapeutic agents.


2017 ◽  
Vol 16 (2) ◽  
pp. 371 ◽  
Author(s):  
Jintana Tragulpakseerojn ◽  
Naoto Yamaguchi ◽  
Perayot Pamonsinlapatham ◽  
Penpun Wetwitayaklung ◽  
Tatsuro Yoneyama ◽  
...  

2013 ◽  
Vol 72 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Lucio Tentori ◽  
Alessia Muzi ◽  
Annalisa Susanna Dorio ◽  
Susanna Dolci ◽  
Federica Campolo ◽  
...  

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