Dorzolamide synergizes the antitumor activity of mitomycin C against Ehrlich’s carcinoma grown in mice: role of thioredoxin-interacting protein

Ali, Belal; Zaitone, Sawsan A.; Shouman, Samia A.; Moustafa, Yasser M.

doi:10.1007/s00210-015-1163-9

Cited by 15 publications

(5 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, DORZOLAMIDE has shown antitumor activity which affects TXNIP-dependent tumour suppression pathways and also causes downregulation in the level of bcl-2 in cancer cells. A previous study also provided evidence for synergistic antitumor activities of DORZOLAMIDE and mitomycinC against Ehrlich ascites carcinoma tumour growth in vivo, and this might offer a potential combination to evaluate in future clinical studies [ 79 ]. It shows that the method was able to suggest new tumour inhibitor drugs for a protein of unknown 3D structure with a crucial role in cancer [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Novel drug-target interactions via link prediction and network embedding

et al. 2022

View full text Add to dashboard Cite

Background As many interactions between the chemical and genomic space remain undiscovered, computational methods able to identify potential drug-target interactions (DTIs) are employed to accelerate drug discovery and reduce the required cost. Predicting new DTIs can leverage drug repurposing by identifying new targets for approved drugs. However, developing an accurate computational framework that can efficiently incorporate chemical and genomic spaces remains extremely demanding. A key issue is that most DTI predictions suffer from the lack of experimentally validated negative interactions or limited availability of target 3D structures. Results We report DT2Vec, a pipeline for DTI prediction based on graph embedding and gradient boosted tree classification. It maps drug-drug and protein–protein similarity networks to low-dimensional features and the DTI prediction is formulated as binary classification based on a strategy of concatenating the drug and target embedding vectors as input features. DT2Vec was compared with three top-performing graph similarity-based algorithms on a standard benchmark dataset and achieved competitive results. In order to explore credible novel DTIs, the model was applied to data from the ChEMBL repository that contain experimentally validated positive and negative interactions which yield a strong predictive model. Then, the developed model was applied to all possible unknown DTIs to predict new interactions. The applicability of DT2Vec as an effective method for drug repurposing is discussed through case studies and evaluation of some novel DTI predictions is undertaken using molecular docking. Conclusions The proposed method was able to integrate and map chemical and genomic space into low-dimensional dense vectors and showed promising results in predicting novel DTIs.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel drug-target interactions via link prediction and network embedding

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Group (4) mice were given a combination of cisplatin and α-hederin at the same time as the monotherapy groups. All treatments were started at day 8 after tumor inoculation and continued for twenty-one days [ 95 , 96 ].…”

Section: Methodsmentioning

confidence: 99%

α-Hederin Saponin Augments the Chemopreventive Effect of Cisplatin against Ehrlich Tumors and Bioinformatic Approach Identifying the Role of SDF1/CXCR4/p-AKT-1/NFκB Signaling

et al. 2023

Self Cite

View full text Add to dashboard Cite

Stromal cell-derived factor-1 (SDF1) and its C-X-C chemokine receptor type 4 receptor (CXCR4) are significant mediators for cancer cells’ proliferation, and we studied their expression in Ehrlich solid tumors (ESTs) grown in mice. α-Hederin is a pentacyclic triterpenoid saponin found in Hedera or Nigella species with biological activity that involves suppression of growth of breast cancer cell lines. The aim of this study was to explore the chemopreventive activity of α-hederin with/without cisplatin; this was achieved by measuring the reduction in tumor masses and the downregulation in SDF1/CXCR4/pAKT signaling proteins and nuclear factor kappa B (NFκB). Ehrlich carcinoma cells were injected in four groups of Swiss albino female mice (Group1: EST control group, Group2: EST + α-hederin group, Group3: EST + cisplatin group, and Group4: EST+α-hederin/cisplatin treated group). Tumors were dissected and weighed, one EST was processed for histopathological staining with hematoxylin and eosin (HE), and the second MC was frozen and processed for estimation of signaling proteins. Computational analysis for these target proteins interactions showed direct-ordered interactions. The dissected solid tumors revealed decreases in tumor masses (~21%) and diminished viable tumor regions with significant necrotic surrounds, particularly with the combination regimens. Immunohistochemistry showed reductions (~50%) in intratumoral NFκβ in the mouse group that received the combination therapy. The combination treatment lowered the SDF1/CXCR4/p-AKT proteins in ESTs compared to the control. In conclusion, α-hederin augmented the chemotherapeutic potential of cisplatin against ESTs; this effect was at least partly mediated through suppressing the chemokine SDF1/CXCR4/p-AKT/NFκB signaling. Further studies are recommended to verify the chemotherapeutic potential of α-hederin in other breast cancer models.

show abstract

“…In the first day, each mouse was inoculated with 0.1 mL of the prepared suspension to induce the solid tumor. The inoculation was done subcutaneously in 2 locations at the ventral side [ 81 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Antitumor Activity of Doxycycline Polymeric Nanoparticles: Effect on Tumor Apoptosis in Solid Ehrlich Carcinoma

et al. 2020

Self Cite

View full text Add to dashboard Cite

Objectives: The aim of this study was to prepare doxycycline polymeric nanoparticles (DOXY-PNPs) with hope to enhance its chemotherapeutic potential against solid Ehrlich carcinoma (SEC). Methods: Three DOXY-PNPs were formulated by nanoprecipitation method using hydroxypropyl methyl cellulose (HPMC) as a polymer. The prepared DOXY-PNPs were evaluated for the encapsulation efficiency (EE%), the drug loading capacity, particle size, zeta potential (ZP) and the in-vitro release for selection of the best formulation. PNP number 3 was selected for further biological testing based on the best pharmaceutical characters. PNP3 (5 and 10 mg/kg) was evaluated for the antitumor potential against SEC grown in female mice by measuring the tumor mass as well as the expression and immunohistochemical staining for the apoptosis markers; caspase 3 and BAX. Results: The biological study documented the greatest reduction in tumor mass in mice treated with PNP3. Importantly, treatment with 5 mg/kg of DOXY-PNPs produced a similar chemotherapeutic effect to that produced by 10 mg/kg of free DOXY. Further, a significant elevation in mRNA expression and immunostaining for caspase 3 and BAX was detected in mice group treated with DOXY-PNPs. Conclusions: The DOXY-PNPs showed greater antitumor potential against SEC grown in mice and greater values for Spearman’s correlation coefficients were detected when correlation with tumor mass or apoptosis markers was examined; this is in comparison to free DOXY. Hence, DOXY-PNPs should be tested in other tumor types to further determine the utility of the current technique in preparing chemotherapeutic agents and enhancing their properties.

show abstract

Dorzolamide synergizes the antitumor activity of mitomycin C against Ehrlich’s carcinoma grown in mice: role of thioredoxin-interacting protein

Cited by 15 publications

References 43 publications

Novel drug-target interactions via link prediction and network embedding

Novel drug-target interactions via link prediction and network embedding

α-Hederin Saponin Augments the Chemopreventive Effect of Cisplatin against Ehrlich Tumors and Bioinformatic Approach Identifying the Role of SDF1/CXCR4/p-AKT-1/NFκB Signaling

Synthesis and Antitumor Activity of Doxycycline Polymeric Nanoparticles: Effect on Tumor Apoptosis in Solid Ehrlich Carcinoma

Contact Info

Product

Resources

About