Etodolac Fortified Sodium Deoxycholate Stabilized Zein Nanoplatforms for Augmented Repositioning Profile in Human Hepatocellular Carcinoma: Assessment of Bioaccessibility, Anti-Proliferation, Pro-Apoptosis and Oxidant Potentials in HepG2 Cells.
Ahmed K KammounMaha A HegazyAlaa KhedrZuhier Ahmed AwanMaan T KhayatMajid Mohammad Al-SawahliPublished in: Pharmaceuticals (Basel, Switzerland) (2022)
This work aimed to enhance the purposing profile of Etodolac (ETD) in Human Hepatocellular Carcinoma (HCC) HepG2 cells using sodium deoxycholate stabilized zein nanospheres (ETD-SDZN NSs). ETD-SDZN NSs were formulated using the nan-precipitation method and were characterized, in particular, in terms of mean particle size, zeta potential, encapsulation efficiency, colloidal stability and bioaccessibility. Estimations of cytotoxicity, cellular uptake, cell cycle progression, Annexin-V staining, mRNA expression of apoptotic genes and oxidative stress evaluations were conducted. The ETD-SDZN NSs selected formula obtained an average particle size of 113.6 ± 7.4 nm, a zeta potential value of 32.7 ± 2.3 mV, an encapsulation efficiency of 93.3 ± 5.2%, enhanced bioaccessibility and significantly reduced IC 50 against HepG2 cells, by approximately 13 times. There was also enhanced cellular uptake, accumulation in G2-M phase and elevated percentage cells in pre-G1 phase, significant elevated mRNA expression of P53, significant reduced expression of Cyclin-dependent kinase 1 (CDK1) and Cyclooxygenase-2 (COX-2) with enhanced oxidative stress by reducing glutathione reductase (GR) level, ameliorated reactive oxygen species (ROS) generation and lipid peroxidation outputs. ETD-SDZN NSs obtained a supreme cell death-inducing profile toward HepG2 cells compared to free ETD. The method of formulation was successful in acquiring the promising profile of ETD in HCC as a therapeutic molecule due to ameliorated cellular uptake, proapoptotic and oxidant potentials.
Keyphrases
- cell death
- cell cycle
- cell cycle arrest
- oxidative stress
- induced apoptosis
- reactive oxygen species
- endothelial cells
- cell proliferation
- dna damage
- anti inflammatory
- poor prognosis
- health risk assessment
- induced pluripotent stem cells
- signaling pathway
- ischemia reperfusion injury
- photodynamic therapy
- genome wide
- pluripotent stem cells
- fatty acid
- diabetic rats
- dna methylation
- climate change
- transcription factor
- risk assessment
- drinking water
- human health
- long non coding rna
- flow cytometry
- nitric oxide synthase
- preterm infants