scholarly journals Pemodelan Farmakofor untuk Identifikasi Inhibitor Heat Shock Proteins-90 (HSP-90)

2020 ◽  
Author(s):  
Muhammad Arba
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Heat Shock ◽  
Binding Energy ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Operating Characteristics ◽  
Hydrogen Bond Donor ◽  
Shock Proteins ◽  
Hsp 90

Heat shock proteins-90 (HSP-90) is a protein that plays an important role in the life cycle of normal and cancer cells for their self protection from thermal stress, oxidative damage, and cell hypoxia. Inhibition of HSP90 is one way to suppress the growth of cancer cells. In this study, pharmacophore modeling and molecular docking were conducted to identify hit compounds as inhibitors of HSP-90. The pharmacophore feature consists of three hydrogen bond acceptors, one hydrogen bond donor and one hydrophobic feature with Area Under Curve of Receiver Operating Characteristics (AUC-ROC) is 0.5 and the Goodness of Hit (GH) value is 0.752. Screening in the ZINC database generated 1,500 hit compounds, were subjected to molecular docking to determine their binding energy and interactions with HSP-90. The range of binding energy (E) of all hit compounds is -5.68 to -12.24 kcal/mol and there are four best hit compounds namely lig_543, lig_527, lig_1337 and lig_337, when compared to native ligands (PU2, E=-8.25 kkal/mol) based on the binding energy and orientation, which indicate their potential as new HSP-90 inhibitors.

scholarly journals Pemodelan Farmakofor untuk Identifikasi Inhibitor Heat Shock Proteins-90 (HSP-90)

2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Muhammad Arba ◽  
Arfan ◽  
Ayu Trisnawati ◽  
Desi Kurniawati
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Heat Shock ◽  
Binding Energy ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Operating Characteristics ◽  
Hydrogen Bond Donor ◽  
Shock Proteins ◽  
Hsp 90

Heat shock proteins-90 (HSP-90) is a protein that plays an important role in the life cycle of normal and cancer cells for their self protection from thermal stress, oxidative damage, and cell hypoxia. Inhibition of HSP90 is one way to suppress the growth of cancer cells. In this study, pharmacophore modeling and molecular docking were conducted to identify hit compounds as inhibitors of HSP-90. The pharmacophore feature consists of three hydrogen bond acceptors, one hydrogen bond donor and one hydrophobic feature with Area Under Curve of Receiver Operating Characteristics (AUCROC) is 0.5 and the Goodness of Hit (GH) value is 0.752. Screening in the ZINC database generated 1,500 hit compounds, were subjected to molecular docking to determine their binding energy and interactions with HSP-90. The range of binding energy (E) of all hit compounds is -5.68 to -12.24 kcal/mol and there are four best hit compounds namely lig_543, lig_527, lig_1337 and lig_337, when compared to native ligands (PU2, E=-8.25 kkal/mol) based on the binding energy and orientation, which indicate their potential as new HSP-90 inhibitors.     

scholarly journals Hsps responsible for apoptosis induction failure in cervical cancer cells upon osthole and tamoxifen treatment

2019 ◽  
Vol 73 ◽  
pp. 563-571
Author(s):  
Joanna Jakubowicz-Gil ◽  
Roman Paduch ◽  
Krystyna Skalicka-Woźniak ◽  
Joanna Sumorek-Wiadro ◽  
Adrian Zając ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cell Lines ◽  
Tamoxifen Treatment ◽  
Hpv 16 ◽  
Cervical Cancer Cells ◽  
Shock Proteins ◽  
Human Cervical Cancer

Aim: The aim of the present study was to investigate the efficacy of osthole (7-metoxy-8-isopenthenocoumarin) alone and combined with tamoxifen (TAM) in the elimination of human cervical cancer cells via programmed death. The involvement of heat shock proteins, i.e. well-known molecular chaperones, will be investigated. Material/Methods: Three human cervical cancer cell lines, infected with human papilloma virus (HPV), i.e. HeLa (HPV 18), SiHa (HPV 16), and CaSki (HPV 16 and 18), were used in the experiments. After osthole and TAM treatment, cells stained with fluorochromes were analyzed microscopically according to apoptotic, autophagic, and necrotic morphology. Hsp27, Hsp72, and Hsp90 levels were analyzed by immunoblotting. Transfection with specific siRNA was used for blocking of Hsp expression. Results: In the HeLa, CaSki, and SiHa cell lines, osthole and TAM applied alone had no significant effect on cell death induction. This was correlated with an overexpression of heat shock proteins 27, 72, and 90. In the case of a combination of both drugs, the level of apoptosis was elevated only in SiHa cells. Preincubation with osthole followed by TAM addition as well as simultaneous incubation with both drugs was the most effective. This was correlated with the inhibition of Hsp27, Hsp72, and Hsp90 expression. Blocking of Hsp expression with specific siRNA increased the sensitivity of the studied cell lines to the induction of apoptosis, but not to autophagy or necrosis. Conclusions: Our results indicated that the elimination of heat shock proteins from cervical cancer cells sensitized them to initiation of apoptosis after osthole and tamoxifen treatment.

scholarly journals Epigenetic Alterations of Heat Shock Proteins (HSPs) in Cancer

2019 ◽  
Vol 20 (19) ◽  
pp. 4758 ◽  
Author(s):  
Hyun Ban ◽  
Tae-Su Han ◽  
Keun Hur ◽  
Hyun-Soo Cho
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cytotoxic Agents ◽  
Epigenetic Alterations ◽  
Regulatory Processes ◽  
Physiological Processes ◽  
Epigenetic Modifiers ◽  
Epigenetic Machinery ◽  
Shock Proteins

Heat shock proteins (HSPs) are associated with various physiological processes (protein refolding and degradation) involved in the responses to cellular stress, such as cytotoxic agents, high temperature, and hypoxia. HSPs are overexpressed in cancer cells and play roles in their apoptosis, invasion, proliferation, angiogenesis, and metastasis. The regulation or translational modification of HSPs is recognized as a therapeutic target for the development of anticancer drugs. Among the regulatory processes associated with HSP expression, the epigenetic machinery (miRNAs, histone modification, and DNA methylation) has key functions in cancer. Moreover, various epigenetic modifiers of HSP expression have also been reported as therapeutic targets and diagnostic markers of cancer. Thus, in this review, we describe the epigenetic alterations of HSP expression in cancer cells and suggest that HSPs be clinically applied as diagnostic and therapeutic markers in cancer therapy via controlled epigenetic modifiers.

Calcium Phosphate Powder for Cancer Vaccination

2007 ◽  
Vol 361-363 ◽  
pp. 1207-1210 ◽  
Author(s):  
Patrick Frayssinet ◽  
Daniel Ciocca ◽  
Nicole Rouquet
Keyword(s):  
T Cells ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cancer Tissue ◽  
Phosphate Powder ◽  
Cancer Vaccination ◽  
Shock Proteins ◽  
Antigen Presenting ◽  
Proteins And Peptides

Cancer cells synthesize abnormal proteins and peptides which are associated to heat shock proteins being overproduced by these cells due to the stress induced by the particular biology of cancer tissue. We have purified on hydroxylapatite powder heat shock proteins using the HAparticles as purification bed, vectors for the proteins and vaccination adjuvant. The powder make possible that the purified HSPs and their associated peptides are transfected to the antigen presenting cells and presented to the T cells for the destruction of the cancer cells bearing the antigens.

scholarly journals Consequences of Atrial or Ventricular Tachypacing on the Heat Shock Proteins (HSP) level of Expression and Phosphorylation

2020 ◽  
Vol 12 (2) ◽  
Author(s):  
Matthew Shorofsky ◽  
Ange Maguy ◽  
Stanley Nattel
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Canine Model ◽  
Right Atrial ◽  
Expression Levels ◽  
Significant Difference ◽  
Canine Models ◽  
Shock Proteins ◽  
Hsp 90

Background - Uncontrolled atrial fibrillation (AF) results in complex changes in the cardiomyocyte electrical and contractile functioning that promote atrial remodeling and the continuation of AF. Recently there has been a growing interest in understanding the role of heat shock proteins (HSPs), which are cytoprotective molecular chaperones, in the pathophysiology of AF. Several groups have examined HSP expression in patients with AF but have yielded mixed results. To allow for  better consistency and reproducibility between subjects, we utilized canine models to reproduce AF- promoting conditions to better investigate the role of HSPs in the pathophysiology of AF. Methods - AF  promoting conditions were simulated in canine models with fifteen adult mongrel dogs (20.6 to 36.0 kg) divided into three groups: (1) Control (n=5), (2) two week ventricular tachypacing (VTP) induced congestive heart failure (CHF) (n=5), and (3) one week atrial tachypacying (ATP) (n=5). Quick frozen right atrial free wall tissue samples were used for protein isolation and were analyzed via Western  blotting with data was expressed as a relative ratio and were analyzed using a two-tailed, unpaired t- test and significance was set at p < 0.05. The expression levels of HSP 90, 70, and 25 were studied along  with the phosphorylation status of HSP27 at serine-78. Results - We first examined the effects of the ATP and CHF heart models on the expression of a select group of HSPs via Western Blot. We found that there was no significant difference in levels of expression of HSP 90, 70, or 25 when either ATP or CHF models were compared to control canines. The phosphorylation status of HSP27 was significantly decreased in the CHF canine model when compared to control (p < 0.0111) and it tended towards a decrease in the ATP canine model when compared to control (p=0.0923). Conclusion - This study showed that even though the expression levels of HSPs may remain constant, there are protein phosphorylation and dephosphorylation events that occur in AF that may have important consequences in its pathophysiology. It is therefore necessary to investigate the full scale of HSP modifications during AF and AF-promoting conditions.

Targeting Heat Shock Proteins on Cancer Cells:  Selection, Characterization, and Cell-Penetrating Properties of a Peptidic GRP78 Ligand†

Biochemistry ◽  
2006 ◽  
Vol 45 (31) ◽  
pp. 9434-9444 ◽  
Author(s):  
Youngsoo Kim ◽  
Antonietta M. Lillo ◽  
Sebastian C. J. Steiniger ◽  
Ying Liu ◽  
Carlo Ballatore ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Cell Penetrating ◽  
Shock Proteins
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