scholarly journals In Silico Docking of Phaleria Macrocarpa Bark Compounds Through Inflammation Pathway and its Cytotoxic Activities Against HCT116 Cell Line

2019 ◽  
Vol 35 (1) ◽  
pp. 471-475
Author(s):  
Aryo Tedjo ◽  
Fadilah Fadilah ◽  
Kusmardi Kusmardi ◽  
Rafika Indah Paramita ◽  
Fadhilah Harmen ◽  
...  
Keyword(s):  
Cell Line ◽  
In Silico ◽  
Hct116 Cell ◽  
Cytotoxic Activities ◽  
Hct116 Cell Line ◽  
In Silico Docking ◽  
Phaleria Macrocarpa

Design, Synthesis, In vitro and In silico Evaluation of New Hydrazonebased Antitumor Agents as Potent Akt Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1380-1392
Author(s):  
Emine Merve Güngör ◽  
Mehlika Dilek Altıntop ◽  
Belgin Sever ◽  
Gülşen Akalın Çiftçi
Keyword(s):  
Cell Line ◽  
Anticancer Agents ◽  
In Silico ◽  
Antitumor Agents ◽  
Colorimetric Assay ◽  
Fibroblast Cell ◽  
Lipinski’S Rule ◽  
In Silico Docking ◽  
Embryonic Fibroblast

Background: Akt is overexpressed or activated in a variety of human cancers, including gliomas, lung, breast, ovarian, gastric and pancreatic carcinomas. Akt inhibition leads to the induction of apoptosis and inhibition of tumor growth and therefore extensive efforts have been devoted to the discovery of potent antitumor drugs targeting Akt. Objectives: The objective of this work was to identify potent anticancer agents targeting Akt. Methods: New hydrazone derivatives were synthesized and investigated for their cytotoxic effects on 5RP7 H-ras oncogene transformed rat embryonic fibroblast and L929 mouse embryonic fibroblast cell lines. Besides, the apoptotic effects of the most active compounds on 5RP7 cell line were evaluated using flow cytometry. Their Akt inhibitory effects were also investigated using a colorimetric assay. In silico docking and Absorption, Distribution, Metabolism and Excretion (ADME) studies were also performed using Schrödinger’s Maestro molecular modeling package. Results and Discussion: Compounds 3a, 3d, 3g and 3j were found to be effective on 5RP7 cells (with IC50 values of <0.97, <0.97, 1.13±0.06 and <0.97 μg/mL, respectively) when compared with cisplatin (IC50= 1.87±0.15 μg/mL). It was determined that these four compounds significantly induced apoptosis in 5RP7 cell line. Among them, N'-benzylidene-2-[(4-(4-methoxyphenyl)pyrimidin- 2-yl)thio]acetohydrazide (3g) significantly inhibited Akt (IC50= 0.5±0.08 μg/mL) when compared with GSK690693 (IC50= 0.6±0.05 μg/mL). Docking studies suggested that compound 3g showed good affinity to the active site of Akt (PDB code: 2JDO). According to in silico ADME studies, the compound also complies with Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 3g stands out as a potential orally bioavailable cytotoxic agent and apoptosis inducer targeting Akt.

scholarly journals Regulation of Transforming Growth Factor α Expression in a Growth Factor-Independent Cell Line

1998 ◽  
Vol 18 (1) ◽  
pp. 303-313 ◽  
Author(s):  
Gillian M. Howell ◽  
Lisa E. Humphrey ◽  
Barry L. Ziober ◽  
Rana Awwad ◽  
Basker Periyasamy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Line ◽  
Antisense Rna ◽  
Promoter Activity ◽  
Transforming Growth Factor ◽  
Hct116 Cell ◽  
Malignant Phenotype ◽  
Hct116 Cell Line ◽  
Transforming Growth Factor Α ◽  
Factor Α

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.

Assessment of the Anticancer and Antigenotoxic potential of Costus speciosus extract against HCT116 cell line

2017 ◽  
Vol 29 (1) ◽  
Author(s):  
Eman Althubaiti ◽  
Abdulkader Shaikh Omar ◽  
Mohammed Almatry ◽  
Yasir Anwar ◽  
Soufyan ElAssouli
Keyword(s):  
Cell Line ◽  
Hct116 Cell ◽  
Hct116 Cell Line ◽  
Costus Speciosus

scholarly journals Pre-treated theaflavin-3,3′-digallate has a higher inhibitory effect on the HCT116 cell line

2017 ◽  
Vol 61 (1) ◽  
pp. 1400340 ◽  
Author(s):  
Yangping Ding ◽  
Bingcan Chen ◽  
Zili Gao ◽  
Huayi Suo ◽  
Hang Xiao
Keyword(s):  
Cell Line ◽  
Hct116 Cell ◽  
Inhibitory Effect ◽  
Hct116 Cell Line

scholarly journals Circulating microRNA-194 and microRNA-1228 Could Predict Colon Cancer Proliferation via Phospho S6 Modulation

2020 ◽  
Vol 29 (3) ◽  
pp. 361-367
Author(s):  
Sergiu Pasca ◽  
Calin Ionescu ◽  
David Andras ◽  
Dan Eniu ◽  
Mihai Andrei Muresan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Western Blotting ◽  
Hct116 Cell ◽  
Cell Counting ◽  
Circulating Microrna ◽  
Cancer Proliferation ◽  
Hct116 Cell Line ◽  
Qrt Pcr ◽  
Advanced Colon Cancer

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.

scholarly journals Qualitative Chemical Characterization and Multidirectional Biological Investigation of Leaves and Bark Extracts of Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae)

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 343 ◽  
Author(s):  
Orlando ◽  
Ferrante ◽  
Zengin ◽  
Sinan ◽  
Bene ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Cell Line ◽  
Hct116 Cell ◽  
Stem Bark ◽  
Rat Colon ◽  
Cholinesterase Inhibition ◽  
Ionization Mass ◽  
Hct116 Cell Line ◽  
Anogeissus Leiocarpus ◽  
Ethyl Acetate Extracts

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.

scholarly journals Anti-proliferative effect of Moringa oleifera Lam (Moringaceae) leaf extract on human colon cancer HCT116 cell line

2017 ◽  
Vol 16 (2) ◽  
pp. 371 ◽  
Author(s):  
Jintana Tragulpakseerojn ◽  
Naoto Yamaguchi ◽  
Perayot Pamonsinlapatham ◽  
Penpun Wetwitayaklung ◽  
Tatsuro Yoneyama ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Leaf Extract ◽  
Moringa Oleifera ◽  
Hct116 Cell ◽  
Human Colon ◽  
Human Colon Cancer ◽  
Hct116 Cell Line ◽  
Proliferative Effect ◽  
Moringa Oleifera Lam

scholarly journals MSH3 expression does not influence the sensitivity of colon cancer HCT116 cell line to oxaliplatin and poly(ADP-ribose) polymerase (PARP) inhibitor as monotherapy or in combination

2013 ◽  
Vol 72 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Lucio Tentori ◽  
Alessia Muzi ◽  
Annalisa Susanna Dorio ◽  
Susanna Dolci ◽  
Federica Campolo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Parp Inhibitor ◽  
Hct116 Cell ◽  
Hct116 Cell Line
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