Green-Synthesis of Cerium Oxide Nanoparticles using Ferula Latisecta Extract: Characterization, Oxidative Stress,...

Colorectal cancer (CRC) remains the main cause of cancer-related mortality worldwide, highlighting the need for effective therapy. Cerium oxide nanoparticles (Cer-NPs) and Ferula latisecta have anticancer properties. This study aimed to green-synthesize of Cer-NPs using Ferula latisecta to assess oxidative stress, apoptosis, and autophagy signaling in CRC cells. The seed extract of Ferula latisecta was combined with cerium salt, synthesized the Cer-NPs, and investigated anticancer effects on human CRC cells with a focus on oxidative stress, apoptosis, and autophagy pathways. XRD, FTIR, and FESEM techniques were utilized to characterize Cer-NPs. HT29 and SW480 CRC cells were treated with a serial dilution of Cer-NPs for cell viability for 24 h and 48 h. Caspase-3 activity assay, AO/PI staining, and real-time PCR method were employed to assess the apoptosis rate and autophagy in cells. Besides, oxidative stress measurements, including intracellular ROS, MDA, LDH, and GSH, were performed. The protein levels of p53 were measured through ELISA. The synthesized Cer-NPs showed a fluorite cubic structure, a crystalline construction, and a spherical morphology with sizes of 20-50 nm. Cer-NPs significantly reduced cell viability in a dose- and time-dependent manner and increased caspase-3 activity (P < 0.05). IC50 values were 0.68 mM and 0.88 mM for HT29 and SW480 cells after 48 h. The number of AO/PI-positive cells was increased alongside ROS production within cells. The levels of MDA and LDH were increased, while the level of GSH was decreased significantly in treated cells (P < 0.05). Furthermore, Cer-NPs could significantly increase Bax, Bcl-2, Beclin-1, P62, Bax/Bcl-2, LC3 II/I ratio as well as up-regulate p53 protein level (P < 0.05). The green-synthesized Cer-NPs could directly induce oxidative stress and apoptosis, and indirectly mediate apoptosis by impairing autophagy.