Chemopreventive potential of linalool in targeting lung cancer biomarkers: An in silico & in vitro investigation

2021 ◽  
Vol 21 ◽  
Author(s):  
Jyoti Singh ◽  
Abha Meena
Keyword(s):  
Lung Cancer ◽  
Antibacterial Properties ◽  
Binding Pocket ◽  
Receptor Interaction ◽  
Docking Analysis ◽  
Lung Cancer Diagnosis ◽  
Lung Adenocarcinoma Cell Line ◽  
In Vitro Investigation ◽  
Drug Receptor

Background: Phytochemicals are used to treat lung cancer in contemporary and traditional medicine. The limitations of known chemotherapeutic drugs such as non-specificity, resistance, and toxicity restrict their use for lung cancer treatment. Therefore, the search for target-specific novel entities is required continuously. Objective: Linalool, a monoterpene alcohol that possesses antiviral, anti-inflammatory, and antibacterial properties, is present in sweet basil, laurel, jasmine, rosewood and lavender. Previous reports revealed its anticancer potential against colon, breast and liver cancer. In this study, linalool's efficacy in targeting biomarkers associated with different lung cancer stages has been investigated Methods: The insilico molecular docking analysis was used to explore drug receptor interaction, and further, linalools cytotoxicity potential was evaluated on lung adenocarcinoma cell line (A549). The toxicity profiling of linalool was done by ADMET analysis. Results: In results Linalool revealed an excellent binding affinity with the selected targets. It showed the highest interaction with BRAF with binding energy -5.6 kcal/mol. Furthermore, it successfully interacts within the binding pocket of BRAF, similar to its inhibitor (Sorafenib). In MTT analysis, linalool significantly reduces the percent viability (IC30 474.94 ± 43.12, 379.33 ± 49.5, and 183.77 ± 66.7 µM in A549 cell lines for 24, 48, and 72 h respectively. Conclusion: These results concluded that linalool possesses chemopreventive potential against lung cancer by interacting or modulating selected biomarkers associated with a lung cancer diagnosis, progression, and proliferation.

scholarly journals Somatostatin and dopamine receptor interaction in prostate and lung cancer cell lines

2010 ◽  
Vol 207 (3) ◽  
pp. 309-317 ◽  
Author(s):  
M Arvigo ◽  
F Gatto ◽  
M Ruscica ◽  
P Ameri ◽  
E Dozio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Membrane Receptors ◽  
Receptor Interaction ◽  
Inhibition Of Proliferation ◽  
Receptor Interactions

Somatostatin analogues inhibit in vitro cell proliferation via specific membrane receptors (SSTRs). Recent studies on transfected cell lines have shown a ligand-induced formation of receptor dimers. The aim of this study is 1) to evaluate the role of specific ligands in modulating receptor interactions in the androgen-dependent prostate cancer cell line, LNCaP, and in the non-small cell lung cancer line, Calu-6, by co-immunoprecipitation and immunoblot; and 2) to correlate the antiproliferative effect of these compounds with their ability in modulating receptor interactions. In LNCaP, we have demonstrated the constitutive presence of sstr1/sstr2, sstr2/sstr5, sstr5/dopamine (DA) type 2 receptor (D2R), and sstr2/D2R dimers. BIM-23704 (sstr1- and sstr2-preferential compound) increased the co-immunoprecipitation of sstr1/sstr2 and significantly inhibited proliferation (−30.98%). BIM-23244 (sstr2–sstr5 selective agonist) significantly increased the co-immunoprecipitation of sstr2/sstr5, and induced a −41.36% inhibition of proliferation. BIM-23A760, a new somatostatin/DA chimeric agonist with a high affinity for sstr2 and D2R and a moderate affinity for sstr5, significantly increased the sstr5/D2R and sstr2/D2R complexes and was the most powerful in inhibiting proliferation (−42.30%). The chimeric compound was also the most efficient in modulating receptor interaction in Calu-6, increasing the co-immunoprecipitation of D2R/sstr5 and inhibiting cell proliferation (−30.54%). However, behind BIM-23A760, BIM-53097 (D2R-preferential compound) also significantly inhibited Calu-6 proliferation (−17.71%), suggesting a key role for D2R in receptor cross talk and in controlling cell growth. Indeed, activation of monomeric receptors did not affect receptor co-immunoprecipitation, whereas cell proliferation was significantly inhibited when the receptors were synergistically activated. In conclusion, our data show a dynamic ligand-induced somatostatin and DA receptor interaction, which may be crucial for the antiproliferative effects of the new analogues.

Myotropic actions of angiotensin and noradrenaline in strips of rabbit aortae

1977 ◽  
Vol 55 (5) ◽  
pp. 1056-1069 ◽  
Author(s):  
J. St-Louis ◽  
D. Regoli ◽  
J. Barabé ◽  
W. K. Park
Keyword(s):  
Late Phase ◽  
Active Form ◽  
Rabbit Aorta ◽  
Residual Effects ◽  
Receptor Interaction ◽  
Wide Range ◽  
High Concentrations ◽  
Drug Receptor ◽  
Time Required

The myotropic effects of angiotensin II (ATII), some analogues and fragments of ATII, and noradrenaline (NA) have been studied in rabbit aorta strips, in vitro. Contractions elicited by NA consist of an initial rapid and of a slow late phase, while ATII produces a slow and gradual increase of tension, especially at low concentrations. A good correlation has been shown to exist between the time required to increase tension by 50% and the concentration of ATII or the pD2 values of various angiotensins. These results suggest that the pattern of the contractions produced by NA and ATII is influenced by the different diffusion rates of the two agents. Aortic strips contracted by NA maintain a stable plateau of contraction for more than 20 min, while tension in those stimulated by maximal concentrations of ATII fades. This fade persists in the presence of indomethacin, of high concentrations of extracellular Ca2+, and does not depend on the metabolism of the peptide.Extracellular Ca2+ plays an important role in the stimulation or rabbit aorta strips by ATII and NA, but does not effect the binding of ATII to its specific receptors over a wide range of concentrations, and reduces slightly the binding of NA. The ratio of maximum response (ATII–NA) is influenced by external Ca2+ and corresponds to 0.54 in the presence of low Ca2+ (0.01 mM), and to 0.86 in the presence of 2.5 mM Ca2+. Both agonists maintain a fraction of their myotropic effect in tissues exposed to Ca2+-free medium for short periods (10−20 min) but are almost inactive after 60 min of Ca2+ deprivation. It is concluded that a fraction of the myotropic effect of both NA and ATII is independent of external Ca2+. Readdition of Ca2+ (1.5 mM) at the peak of the residual effects obtained in absence of Ca2+ restores full control response to both agents. When the same intervention is repeated at different times after washout of the drug only the strips treated with ATII show a progressively decreasing contractile response. This indicates that ATII remains in the active form in the proximity of the receptors for several minutes after washing, while NA does not.The administration of the antagonists (8-Gly-ATII for ATII and phentolamine for NA) or the removal of external Ca2+ while maintaining the infusion of the two stimulants is followed by relaxations more rapid than that produced by the washout of ATII, but not of NA. A good correlation has been shown to exist between the rates of the relaxations induced by 8-Gly-ATII and the pD2 values of various angiotensins.The results suggest that the major difference between the actions of ATII and NA in rabbit aortae resides in the duration of the drug−receptor interaction. The drug−receptor complex of the peptide appears to be more stable than that of the catecholamine and this may explain the higher (with respect to NA) affinity of ATII for its aortic receptors.

scholarly journals Dysregulation of ferroptosis may involve in the development of non-small cell lung cancer in Xuanwei area

2020 ◽  
Author(s):  
Zhang Yang ◽  
Guangjian Li ◽  
Jiapeng Yang ◽  
Guangqiang Zhao ◽  
Zhenghai Shen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Indoor Air Pollution ◽  
Protein Profiling ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Differentially Expressed Proteins ◽  
Tandem Mass Tag ◽  
Differential Proteins ◽  
Local Residents

Abstract Background The Xuanwei area of Yunnan Province, China is one of the regions with the highest incidence of lung cancer in the world. Local residents use bituminous coal as fuel for cooking and heating, which causes serious indoor air pollution. After the local government carried out furnace and stove reform work, the high incidence of lung cancer in residents continued. We herein wonder if there are specific mechanisms at protein level for the development of lung cancer in the area. Methods We investigated the changes of protein profiling in tumor of the patients from Xuanwei area. Tandem Mass Tag (TMT) were employed to screen the differential proteins between carcinoma and para-carcinoma tissues. Results We identified a total of 422 differentially-expressed proteins, among which 162 proteins were significantly upregulated and 260 were downregulated compared to para-carcinoma tissues. Many of the differentially-expressed proteins were related to ECM-receptor interaction, focal adhesion, PI3K/AKT pathway and ferroptosis. Further experiments on the two differential proteins, TXN2 and HP, showed that the change of their expressions could make the lung cancer cell lines more resistant to erastin or RSL-induced ferroptosis in vitro, and promote the growth of tumor in nude mice. Conclusion This study revealed that aberrant regulation of ferroptosis may involve in the development of lung cancer in Xuanwei area.

In vitro investigation of Varizella zoster virus as an oncolytic virus in glioblastoma therapy

2008 ◽  
Vol 35 (S 01) ◽  
Author(s):  
H Leske ◽  
A Baiker ◽  
C Schichor ◽  
J.C Tonn ◽  
R Goldbrunner ◽  
...  
Keyword(s):  
Oncolytic Virus ◽  
In Vitro Investigation ◽  
Varizella Zoster Virus

Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

2017 ◽  
Vol 9 (5) ◽  
Author(s):  
Jaynthy C. ◽  
N. Premjanu ◽  
Abhinav Srivastava
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
In Silico ◽  
Computational Study ◽  
Regulation Mechanism ◽  
Down Regulation ◽  
Fruit Extract ◽  
In Vitro Techniques ◽  
Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

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