RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells

Abstract

Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.

Repurposing of Sitagliptin- Melittin Optimized Nanoformula against SARS-CoV-2; Antiviral Screening and Molecular Docking Studies

“…Pointing out the formulation and process parameters that influence the drug delivery system characteristics is fundamental in the area of pharmaceutical formulation [74][75][76][77]. Factorial design is helpful in this aspect by jointly analyzing the effect of various factors.…”

“…The effectiveness of the absorption process can be influenced by changes in the physical properties of the NPs, as well as by differences in the characteristics of the cellular membrane. Pointing out the formulation and process parameters that influence the drug delivery system characteristics is fundamental in the area of pharmaceutical formulation [ 74 , 75 , 76 , 77 ]. Factorial design is helpful in this aspect by jointly analyzing the effect of various factors.…”

“…NPs zeta potential, a surface charge indicator, has a great impact in crossing the cell membrane (negatively charged). Additionally, NPs zeta potential has a role in improving NPs solution stability and preventing aggregation of the NPs [ 64 , 77 , 80 ]. Zeta potential indicates the charge stabilization of nanoparticulate systems.…”

Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance

“…In a nude mouse model, fluvastatin prevented lung adenocarcinoma bone metastasis, which is largely dependent on p53-mediated autophagy induction [ 81 ]. Fluvastatin conjugated with human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) produces anti-proliferative action against human hepatoma cancer cells through a concomitant accumulation of cells in the pre-G phase and induction of caspase 3 cleavage [ 82 ]. Atorvastatin causes strong growth inhibition of epithelial- and mixed epithelial-mesenchymal cancer cells by inhibiting the protein prenylation pathway [ 83 ].…”

Molecular docking studies of HIV TAT and sitagliptin nano-formula as potential therapeutic targeting SARS-CoV2 protease

“…The Trans-Activator Transcription peptide (TAT) of of HIV1 has set off a whole generation of intra-cellular delivery of loaded therapeutics [ [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. The TAT peptide which is rich with positively charged amino acids is utilized as a research tool to improve the transport and delivery of the drugs, DNA, proteins, RNA, nanoparticles and viruses in the cytoplasm [ [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] ]. These anti-COVID-19 drugs’ efficacy can be enhanced by associating it with TAT peptide [ 32 ].…”