Potential of Orlistat to induce apoptotic and antiangiogenic effects as well as inhibition of fatty acid synthesis in breast cancer cells

Jovankić, Jovana; Nikodijević, Danijela D.; Milutinović, Milena; Nikezić, Aleksandra G.; Kojić, Vesna; Cvetković, Aleksandra; Cvetković, Danijela

doi:10.1016/j.ejphar.2022.175456

Cited by 13 publications

(9 citation statements)

References 51 publications

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“…In a sterile 96‐well plate, 5 × 10 3 cells were inoculated at 180 μL per well 29 . With reference to the study by Jovankić et al 30 the cells were incubated with 0.016, 0.08, 0.4, 2, and 10 μg/mL of DOX, P(PFPHM 9 ‐ b ‐DMAEMA‐ b ‐PEGMEA 480 ) and DOX‐loaded micelles P(PFPHM 9 ‐ b ‐DMAEMA‐ b ‐PEGMEA 480 )‐DOX at 37°C for 48 h, respectively. MTT (20 μL, 5.0 g/L) was added and incubated for 4 h after which all solutions were removed.…”

Section: Methodsmentioning

confidence: 99%

Preparation and characterization of pH and thermally responsive perfluoropolyether acrylate copolymer micelles and investigation its drug‐loading properties

Lin

et al. 2023

J of Applied Polymer Sci

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In this study, pH and thermally responsive P(PFPHM 9 -b-DMAEMA-b-PEG-MEA 480 ) was prepared by atom transfer radical polymerization (ATRP) using perfluoropolyether hydroxyethyl methacrylate (PFPHM) as hydrophobic core, 2-(Dimethylamino) ethyl methacrylate as pH and thermal response function segment, and poly (ethylene glycol) methyl ether acrylate 480 as hydrophilic shell, respectively. The chemical structure, critical micelle concentration (CMC), lower critical solution temperature (LCST), biological toxicity, stability of micelles, drug-loading performance and cumulative drug release rate of prepared P(PFPHM 9 -b-DMAEMA-b-PEGMEA 480 ) were analyzed by 19 F NMR, 1 H NMR, FTIR, DLS, UV-Vis, laser confocal microscopy and fluorescence spectrophotometer. The results show that P(PFPHM 9 -b-DMAEMA-b-PEGMEA 480 ) exhibites a CMC of 7.5 g/L, LCST of 37.6 C and excellent micelle stability.Moreover, the analysis of drug-loading indicates that the polymer displayed drug loading efficiency (DL) is 21.3% and the encapsulation efficiency (EE) is 90.0%. Its cumulative drug release rates at pH = 6.5 (42 C) is almost double of those at pH = 7.4 (42 C), pH = 6.5 (37 C) and pH = 7.4 (37 C). These results suggeste that the P(PFPHM 9 -b-DMAEMA-b-PEGMEA 480 ) at pH ranging from 6.5 to 7.4 and temperature ranging from 37 to 42 C are pH and temperature sensitive. It has great potential application as a drug loading for DOX.amphiphilicity, drug-loading, lower critical solution temperature, perfluoropolyether acyl fluoride, pH and thermal responsiveness | INTRODUCTIONCancer has attracted widespread attention as one of the major threats to human health. Despite the significant progress made in current cancer treatment, a complete cure remains a thorny issue. 1 Chemotherapy is one of effective treatments for cancer, but the non-specific behavior of chemotherapy drugs can damage normal tissue cells, resulting in toxic side effects for patients. 2 Therefore, it is crucial to improve the utilization and selectivity of drugs on cancer cells. 3 Drug-loaded micelles formed by self-assembly of amphiphilic polymers as DDS have great potential for the treatment of cancer with good biocompatibility, high

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Section: Methodsmentioning

confidence: 99%

Preparation and characterization of pH and thermally responsive perfluoropolyether acrylate copolymer micelles and investigation its drug‐loading properties

Lin

et al. 2023

J of Applied Polymer Sci

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“…The antiproliferative activity for 3-cyanopyridin-2-one derivatives (6a-m and 8a-d) was evaluated against HeLa and MDA-MB-231 cells, following the procedures of the MTT assay. [42][43][44][45] The antiproliferative activity of phenyl-substituted 3-cyanopyridin-2-one derivatives (6a-m) against MDA-MB-231 and HeLa cancer cells range from 4.63 µM down to 0.13 µM from 4.32 µM down to 0.12 µM, respectively.…”

Section: Hela and Mda-mb-231 Cells Antiproliferative Activitymentioning

confidence: 99%

Identification of 3‐(5‐cyano‐6‐oxo‐pyridin‐2‐yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity

Shaldam,

Khalil,

Almahli

et al. 2023

Archiv der Pharmazie

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New 5‐cyano‐6‐oxo‐pyridine‐based sulfonamides (6a–m and 8a–d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5‐cyanopyridine derivatives 6e and 6l on cell‐cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.

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“…The lipase inhibitor orlistat (ORL) prevents the fatty acid synthase (FAS) enzyme from activating its thioesterase domain, which is especially upregulated in many tumor cells, and its inhibition has been shown to suppress tumor growth and metastasis [ 1 , 2 ]. Several studies have revealed elevated FAS in different cancer types compared with normal tissues [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice

Alamoudi,

El-Masry,

Nasr

et al. 2024

Pharmaceuticals

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Background: Orlistat (ORL) is an effective irreversible inhibitor of the lipase enzyme, and it possesses anticancer effects and limited aqueous solubility. This study was designed to improve the aqueous solubility, oral absorption, and tissue distribution of ORL via the formulation of nanocrystals (NCs). Methods: ORL-NC was prepared using the liquid antisolvent precipitation method (bottom-up technology), and it demonstrated significantly improved solubility compared with that of the blank crystals (ORL-BCs) and untreated ORL powder. The biodistribution and relative bioavailability of ORL-NC were investigated via the radiolabeling technique using Technetium-99m (99mTc). Female Swiss albino mice were used to examine the antitumor activity of ORL-NC against solid Ehrlich carcinoma (SEC)-induced hepatic damage in mice. Results: The prepared NCs improved ORL’s solubility, bioavailability, and tissue distribution, with evidence of 258.70% relative bioavailability. In the in vivo study, the ORL-NC treatment caused a reduction in all tested liver functions (total and direct bilirubin, AST, ALT, and ALP) and improved modifications in liver sections that were marked using hematoxylin and eosin staining (H&E) and immunohistochemical staining (Ki-67 and ER-α) compared with untreated SEC mice. Conclusions: The developed ORL-NC could be considered a promising formulation approach to enhance the oral absorption tissue distribution of ORL and suppress the liver damage caused by SEC.

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Potential of Orlistat to induce apoptotic and antiangiogenic effects as well as inhibition of fatty acid synthesis in breast cancer cells

Cited by 13 publications

References 51 publications

Preparation and characterization of pH and thermally responsive perfluoropolyether acrylate copolymer micelles and investigation its drug‐loading properties

Preparation and characterization of pH and thermally responsive perfluoropolyether acrylate copolymer micelles and investigation its drug‐loading properties

Identification of 3‐(5‐cyano‐6‐oxo‐pyridin‐2‐yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity

Fabrication of Nanocrystals for Enhanced Distribution of a Fatty Acid Synthase Inhibitor (Orlistat) as a Promising Method to Relieve Solid Ehrlich Carcinoma-Induced Hepatic Damage in Mice

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