Antiproliferative Activity of Cissus quadrangularis L. Extract against Human Cervical Cancer Cells: In Vitro and In Silico Analysis

2021 ◽  
Vol 21 ◽  
Author(s):  
Sahabjada Siddiqui ◽  
Qamar Zia ◽  
Mohd Abbas ◽  
Sushma Verma ◽  
Asif Jafri ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Viability ◽  
Hela Cells ◽  
In Silico ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Ros Generation ◽  
Dependent Manner ◽  
Cissus Quadrangularis ◽  
Silico Analysis

Background: Ce rvical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents. Objective: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. Methods: Cell viability was analyzed in HeLa cells at different concentrations (25-300 μg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK. Results: Cell viability of HeLa cells was reduced significantly (p ˂ 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski’s Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. Conclusion: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.

Assessment of epigenetic alterations and in silico analysis of mutation affecting PTEN expression among Indian cervical cancer patients

2019 ◽  
Vol 120 (9) ◽  
pp. 15851-15866 ◽  
Author(s):  
Afreen Naseem ◽  
Zafar Iqbal Bhat ◽  
Ponnusamy Kalaiarasan ◽  
Bhupender Kumar ◽  
Zubair Bin Hafeez ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Patients ◽  
In Silico ◽  
In Silico Analysis ◽  
Pten Expression ◽  
Epigenetic Alterations ◽  
Silico Analysis

scholarly journals Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Shoaib Shoaib ◽  
Saba Tufail ◽  
Mohammad Asif Sherwani ◽  
Nabiha Yusuf ◽  
Najmul Islam
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Therapeutic Potential ◽  
Ros Generation ◽  
Main Concern ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Phenethyl Isothiocyanate ◽  
Cervical Cancer Cells

The latest research shows that current chemotherapeutics are ineffective because of the development of resistance in cervical cancer cells, and hence, their scope of use is limited. The main concern of researchers at the moment is the discovery of safe and effective antiproliferative plant chemicals that can aid in the battle against cervical cancer. Previous studies have shown the possible anticancer potential of phenethyl isothiocyanate obtained from cruciferous plants for many cancers, which targets various signaling pathways to exercise chemopreventive and therapeutic effects. This provides the basis for studying phenethyl isothiocyanate's therapeutic potential against cervical cancer. In the present study, cervical cancer cells were treated with various doses of phenethyl isothiocyanate, alone and in combination with cisplatin. Phenethyl isothiocyanate alone was sufficient to cause nucleus condensation and fragmentation and induce apoptosis in cervical cancer cells, but evident synergistic effects were observed in combination with cisplatin. In addition, phenethyl isothiocyanate treatment increased the production of intracellular ROS in a dose-dependent manner in cervical cancer cells. Furthermore, investigation of phenethyl isothiocyanate induced mitochondrial reactive oxygen species production, and activation of caspases showed that phenethyl isothiocyanate significantly activated caspase-3.

scholarly journals Identification of HPV16 in suspected cases of cervical lesions and docking Study of its L1 protein with some natural inhibitors.

2020 ◽  
Author(s):  
Yusuf Lukman ◽  
Doro Aliyu Bala ◽  
Kabir Imam Malik ◽  
Abdulkadir Saidu ◽  
Abdulhadi Sale Kumurya ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
High Risk ◽  
Prevalence Rate ◽  
In Silico ◽  
In Silico Analysis ◽  
Low Grade ◽  
Cervical Lesions ◽  
Hpv 16 ◽  
L1 Protein ◽  
Silico Analysis

Abstract Background The Human papillomavirus (HPV) causes sexually transmitted diseases. Among several types of HPV variants, HPV 16 is listed as a high-risk group, the primary cervical cancer etiologic agent, which causes life-threatening disease among women worldwide. The presence of L1, E6 and E7 encoded oncoproteins are largely responsible for virulence and pathogenicity that leads to cervical lesions. This menace is required to be curbed by designing an anti-cancerous drugs. The protein receptor-inhibitor interaction adopted using in silico analysis is very important in drug designing. It was the objective of this study to identify HPV16 isolates from suspected cases of cervical cancer at SH Sokoto and SYMH Birnin Kebbi hospitals and also to identify potent HPV16’s L1 protein inhibitor using in silico analysis of Echinacoside, curcumin and Cichoric acid against the viral protein. Methods A total of 140 cervical smear samples consisting of 21 low grade squamous intraepithelial lesion, 6 high grade lesion and 117 negative pap smears were collected. The samples were subjected for molecular detection using PCR targeting E6 and L1 genes of the virus. Positive samples were sequenced using Sanger sequencing platform. All the sequencing data were analysed using bioedit software while data generated for the molecular prevalence was statistically analyzed using Chi-square. A comprehensive HPV L1 protein homology model was designed to predict the L1 protein interaction mechanism with natural inhibitory molecules using a structural drug design approach. AutoDock Vina was used to carry out the molecular docking. Results Out of the 140 samples, 24 samples were positive for the PCR representing 16.7% molecular prevalence rate. There is statistically significant association between cyto-diagnoses and presence of HPV16 ( P ˂0.05). The highest prevalence rate of 12(50% of positive sample) was recorded among women between 30-39 years old. Docking analysis showed that the Chicoric acid components of Echinacea purpurae have strong binding affinity to the L1 protein of the HPV. Conclusion This study provides data on HPV 16 epidemiology in northern Nigeria, High-risk type 16 HPV variant was identified and also provides novel evidence for consideration on certain interacting residues, when synthesizing Anti-HPV compounds in the wet lab.

scholarly journals Proapoptosis Effect of Root of Eurycoma longifolia (Pasak Bumi) on the Prostate Cancer: In Silico Analysis

2020 ◽  
Vol 20 ◽  
pp. 03003
Author(s):  
Eka Yudha Rahman ◽  
Mulyohadi Ali ◽  
Basuki Bambang Purnomo ◽  
Nia Kania
Keyword(s):  
Prostate Cancer ◽  
In Silico ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Data Bank ◽  
Active Ingredients ◽  
Caspase 9 ◽  
Active Compounds ◽  
Eurycoma Longifolia ◽  
Silico Analysis

This study aimed to predict the proapoptosis effect of E. longifolia active compounds on prostate cancer by in silico analysis. Protein data such as BCL-2 (GI: 2506216), Caspase 3 (GI: 6978605), Caspase 8(GI: 11560103), data quassinoid (ID: 5459060 and chantin (ID: 97176) were collected from GenBank of NCBI. Protein BCL-2 collected from NCBI compare with Protein Data Bank (PDB) and UNIPROT. The docking process was carried out using software HEX 8.0. to compute the binding affinity between ligands (active compounds of Pasak Bumi) and protein target. The interaction between quassinoid and chantin was strongest and stable against caspase-9, indicating that the active ingredient in E. longifolia triggered caspase-9 activity after activation of BH3 domains in Bcl-2 in prostate cancer. The low energy binding between quassinoid and chantin with caspase-3 indicates the interaction between the active ingredients is not strong with caspase-3. E. longifolia active ingredients that are potentially used in the treatment of prostate cancer are quassinoid and chantin by inducing apoptotic mechanisms via both extrinsic and intrinsic pathways. The combination of active ingredients of E. longifolia that is quassinoid and chantin can be used as a strategy of prostate cancer therapy both through extrinsic and intrinsic pathways.

scholarly journals miR-22 Modulates Lenalidomide Activity by Counteracting MYC Addiction in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4365
Author(s):  
Daniele Caracciolo ◽  
Caterina Riillo ◽  
Giada Juli ◽  
Francesca Scionti ◽  
Katia Todoerti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Western Blot ◽  
Cell Viability ◽  
Chromatin Immunoprecipitation ◽  
In Silico ◽  
Synthetic Lethality ◽  
Inverse Correlation ◽  
In Silico Analysis ◽  
Predictive Biomarker ◽  
Silico Analysis

Background: MYC is a master regulator of multiple myeloma (MM) by orchestrating several pro-tumoral pathways, including reprograming of the miRNA transcriptome. MYC is also involved in the acquirement of resistance to anti-MM drugs, including immunomodulatory imide drugs (IMiDs). Methods: In silico analysis was performed on MM proprietary and on public MMRF-CoMMpass datasets. Western blot and chromatin immunoprecipitation (ChIP) experiments were performed to validate miR-22 repression induced by MYC. Cell viability and apoptosis assays were used to evaluate lenalidomide sensitization after miR-22 overexpression. Results: We found an inverse correlation between MYC and miR-22 expression, which is associated with poor outcome in IMiD-treated MM patients. Mechanistically, we showed that MYC represses transcription of miR-22, which, in turn, targets MYC, thus establishing a feed-forward loop. Interestingly, we found that IMiD lenalidomide increases miR-22 expression by reducing MYC repression and, most importantly, that the combination of lenalidomide with miR-22 mimics results in a synergistic direct and NK-mediated cytotoxic activity. Conclusions: Taken together, our findings indicate that: (1) low miR-22 expression could represent a potential predictive biomarker of poor lenalidomide response in MM patients; and (2) miR-22 reduces MYC oncogenic activity, thus triggering a novel synthetic lethality loop, which sensitizes MM cells to lenalidomide.

The association of the placental CASPASE‐3 gene polymorphisms and preeclampsia susceptibility and in‐silico analysis

2018 ◽  
Vol 119 (8) ◽  
pp. 6756-6764 ◽  
Author(s):  
Batool Teimoori ◽  
Atefeh Yazdi ◽  
Mahnaz Rezaei ◽  
Abbas Mohammadpour‐Gharehbagh ◽  
Danial Jahantigh ◽  
...  
Keyword(s):  
In Silico ◽  
Gene Polymorphisms ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Silico Analysis

scholarly journals In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host

2013 ◽  
Vol 9 (9) ◽  
pp. 456-463 ◽  
Author(s):  
Shakti Kumar ◽  
◽  
Devendra Kumar Biswal ◽  
Veena Tandon
Keyword(s):  
In Silico ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Human Host ◽  
Silico Analysis

Epigallocatechin Gallate Protects against TNFα- or H2O2- Induced Apoptosis by Modulating Iron Related Proteins in a Cell Culture Model

2018 ◽  
Vol 88 (3-4) ◽  
pp. 158-165 ◽  
Author(s):  
Qi Xu ◽  
Anumantha G. Kanthasamy ◽  
Manju B. Reddy
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Caspase 3 ◽  
Epigallocatechin Gallate ◽  
Ros Generation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Cell Viability Assay ◽  
Hepcidin Expression

Abstract. Oxidative stress, iron dysregulation, and inflammation have been implicated in the pathogenesis of Parkinson’s disease (PD). Considering the entwined relationship among these factors, epigallocatechin gallate (EGCG) may be a good candidate for PD treatment due to its protective effects against those factors. The objective of this study is to determine whether EGCG protects N27 dopaminergic neuronal cells from H2O2 - and TNFα- induced neurotoxicity. Seven treatments were included: control, H2O2, TNFα, FeSO4, H2O2 + EGCG, TNFα + EGCG, FeSO4 + EGCG. Cells were pretreated with 10 μM EGCG, followed by 50 μM H2O2, 30 ng/ml TNFα or 50 μM FeSO4. Neuroprotective effects of EGCG were assessed by cell viability assay, caspase-3 activity, intracellular reactive oxygen species (ROS) generation, and iron related protein expressions. Caspase-3 activity was increased to 2.8 fold (P < 0.001) and 1.5 fold (P < 0.01) with H2O2 and TNFα treatment; However, EGCG pretreatment significantly decreased the caspase activity by 50.2% (P < 0.001) and 30.1% (P < 0.05). Similarly, cell viability was reduced to 69.2% (P < 0.01) and 89% (P < 0.01) by H2O2 and TNFα, which was partially blocked by EGCG pretreatment. Also, EGCG significantly (P < 0.001) protected against H2O2- induced ROS in a time dependent manner. In addition, both H2O2 and TNFα significantly (P < 0.05) upregulated hepcidin expression and marginally reduced ferroportin (Fpn) expression unlike iron treatment alone. Collectively, our results show that EGCG protects against both TNFα- and H2O2- induced neuronal apoptosis. The observed neuroprotection may be through the inhibition of oxidative stress and inflammation which is possibly mediated mainly by hepcidin and partially by Fpn.

scholarly journals TP73 G4C14-A4T14 polymorphism and cancer susceptibility: evidence from 36 case–control studies

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jialin Meng ◽  
Shuo Wang ◽  
Meng Zhang ◽  
Song Fan ◽  
Li Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cervical Cancer ◽  
In Silico ◽  
Cancer Susceptibility ◽  
Meta Analysis ◽  
In Silico Analysis ◽  
Case Control ◽  
Genetic Models ◽  
Case Control Studies ◽  
Silico Analysis

G4C14-A4T14 polymorphism of TP73 gene has been reported with a potential association in cancer risks through affected cell homeostasis; however the results were not consistent. We performed a comprehensive meta-analysis to explore the associations between G4C14-A4T14 polymorphism and cancer susceptibility. Extensive retrieve was performed in PubMed, EMBASE, Google Scholar, Web of Science, Wanfang database and CNKI database up to May 20, 2018. Odds ratios (ORs) and 95% confidence intervals (CIs) were conducted to evaluate the overall strength of the associations in five genetic models, as well as in subgroup analyses. Q-test, false-positive report probability analysis and trial sequential analysis, Egger’s test and Begg’s funnel plot were applied to evaluate the robustness of the results. In silico analysis was managed to demonstrate the relationship of TP73 expression correlated with cancer tissues. Finally, 36 case–control studies with a total of 9493 cancer cases and 13,157 healthy controls were enrolled into the meta-analysis. The pooled results present a significantly higher risk of G4C14-A4T14 polymorphism in all the five genetic models, as well as in the subgroups of Caucasian, cervical cancer, colorectal cancer, H-B subgroup and comfort to Hardy–Weinberg equilibrium subgroup. In silico analysis revealed that the expression of TP73 in cervical cancer tissue is higher than it in corresponding normal tissue, as well as in cervical cancer. All in all, TP73 G4C14-A4T14 polymorphism causes an upgrade cancer risk, especially in Caucasian population. G4C14-A4T14 polymorphism might be a potential biomarker for judging the tumorigenesis of cervical cancer and colorectal cancer.

scholarly journals A Report on Multi-Target Anti-Inflammatory Properties of Phytoconstituents from Monochoria hastata (Family: Pontederiaceae)

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7397
Author(s):  
Md Mazedul Haq ◽  
Md Arifur Rahman Chowdhury ◽  
Hilal Tayara ◽  
Ibrahim Abdelbaky ◽  
Md Shariful Islam ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Control Group ◽  
Dependent Manner ◽  
In Vivo Experiments ◽  
Microbial Infections ◽  
Anti Inflammatory ◽  
Silico Analysis

This study aims to investigate the potential analgesic properties of the crude extract of Monochoria hastata (MH) leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a moderate analgesic property (~54% pain inhibition in acetic acid-induced writhing test), which is significant (** p < 0.001) as compared to the control group. The complex inflammatory mechanism involves diverse pathways and they are inter-connected. Therefore, multiple inflammatory modulator proteins were selected as the target for in silico analysis. Computational analysis suggests that all the selected targets had different degrees of interaction with the phytochemicals from the extract. Rutin (RU), protocatechuic acid (PA), vanillic acid (VA), and ferulic acid (FA) could regulate multiple targets with a robust efficiency. None of the compounds showed selectivity to Cyclooxygenase-2 (COX-2). However, regulation of COX and lipoxygenase (LOX) cascade by PA can reduce non-steroidal analgesic drugs (NSAIDs)-related side effects, including asthma. RU showed robust regulation of cytokine-mediated pathways like RAS/MAPK and PI3K/NF-kB by inhibition of EGFR and IKBα (IKK), which may prevent multi-organ failure due to cytokine storm in several microbial infections, for example, SARS-CoV-2. Further investigation, using in vivo and in vitro experiments, can be conducted to develop multi-target anti-inflammatory drugs using the isolated compounds from the extract.

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