Al-Malki, Abdulrahman LBakkar, AshrafHuwait, EtimadBarbour, Elie KAbulnaja, Kalid OKumosani, Taha AMoselhy, Said S2021-08-072021-08-0708/02/2021https://doi.org/10.1016/j.biopha.2021.111960https://qrgo.page.link/vckAiBiomedicine & Pharmacotherapy Volume 142, October 2021, 111960 Strigol1/albumin/chitosan nanoparticles decrease cell viability, induce apoptosis and alter metabolomics profile in HepG2 cancer cell line Author links open overlay panelAbdulrahman L.Al-MalkiabcAshrafBakkardEtimad A.HuwaitaElie K.BarbourabeKalid O.AbulnajaabcTaha A.KumosaniabfSaid S.Moselhyg a Biochemistry Department, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia b Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Saudi Arabia c Bioactive Natural Products Research Group, King Abdulaziz University. Jeddah, Saudi Arabia d Modern Sciences and Arts University (MSA), 6th October, Giza, Egypt e Director of R and D Department, Opticon Hygiene Consulting, Oechsli 7, 8807 Freienbach, Switzerland f Production of Bio-products for Industrial Applications Research Group, King Abdulaziz University g Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt Received 16 March 2021, Revised 21 July 2021, Accepted 22 July 2021, Available online 2 August 2021. crossmark-logo https://doi.org/10.1016/j.biopha.2021.111960 Get rights and content Under a Creative Commons licenseopen access Highlights • Novel strigol nanoparticles (S/A/CNP) exhibit antiproliferative activity against HepG2 cells through dose dependent. • The S/A/CNP significantly reduces Krebs cycle intermediate and decrease glutamine level as energy source substrate. • The S/A/CNP induce morphological changes and trigger pro-apoptotic effects in HepG2. • The S/A/CNP reduces spermine and spermidine and inhibit DNA replication. Abstract Hepatocellular carcinoma is one of the most common causes of cancer-related deaths globally. Bioavailable, effective and safe therapeutic agents are urgently needed for cancer treatment. This study evaluated the metabolomics profiling, anti-proliferative and pro-apoptotic effects of strigol/albumin/chitosan nanoparticles (S/A/CNP) on HepG2 cell line. The diameter of S/A/CNP was (5 ± 0.01) nm. The IC50 was 180.4 nM and 47.6 nM for Strigol1 and S/A/CNP, respectively, after incubation for 24 h with HepG2 cells. By increasing the concentration of S/A/CNP, there was chromatin condensation, degranulation in the cytoplasm and shrinking in cell size indicating pro-apoptotic activity. Metabolomics profiling of the exposed cells by LC/MS/MS revealed that S/A/CNP up-regulated epigenetic intermediates (spermine and spermidine) and down-regulated energy production pathway and significantly decreased glutamine (P < 0.001). These findings demonstrated that S/A/CNP has anti-proliferative, apoptotic effects and modulate energetic, and epigenetic metabolites in the hepatocellular carcinoma cell line (HepG2).en-USStrigol 1NanoparticlesMetabolomicsApoptosisHepG2Articlehttps://doi.org/10.1016/j.biopha.2021.111960