Regulation of the PI3K/AKT/mTOR signaling pathway with synthesized bismuth oxide nanoparticles from Ginger (Zingiber officinale) extract: Mitigating the proliferation of colorectal cancer cells

Abstract

In order to overcome the limitations of conventional therapeutic systems in the treatment of cancer, nanoparticles (NPs) have been rapidly produced and developed as a separate treatment method for control of cancer. Synthesis of nanoparticles using plant-based materials (green synthesis), due to the easy and cost-effective synthesis, production of non-toxic, sustainable and environmentally friendly products, can be considered the most appropriate method for preparation of NPs. In this study, after synthesis of Bi 2 O 3 NPs using Ginger ( Zingiber officinale ) root (rhizome) extract, the synthesized NPs were characterized and their potential application as selective anticancer agents against HCT116 colorectal cancer cells was evaluated through regulation of PI3K/AKT/mTOR signaling pathway, whereas the human kidney (HK-2) cells were used as normal cells. FTIR analysis showed a band at 673 cm −1 attributed to Bi-O vibration with a fingerprint region at 1291 cm −1 demonstrating the attachment of the organic molecules to the synthesized Bi 2 O 3 NPs. UV–visible study showed a λ max of around 268 nm, whereas XRD analysis showed eight clear peaks, demonetizing the crystalline phase of synthesized Bi 2 O 3 NPs. TEM analysis showed that spherical-shaped Bi 2 O 3 NPs have a size range of 20–50 nm with a man size of around 35 nm. Finally, DLS analysis determined that Bi 2 O 3 NPs have a hydrodynamic size of about 71.19 nm (PDI of 0.179) and a zeta potential value of −44.39 mV, revealing the good colloidal stability of NPs. Cellular assays (MTT, LDH, flow cytometry, and RT-qPCR) showed that synthesized Bi 2 O 3 NPs selectively induced anticancer effects against HCT116 colorectal cancer cells through membrane leakage, generation of ROS, induction of apoptosis via dysregulation of Bax, Bcl-2 and caspase-3 at mRNA level mediated via regulation of PI3K/AKT/mTOR signaling pathway. In conclusion, it may be suggested that the presence study could provide useful information for the potential anticancer effects mediated by synthesized Bi 2 O 3 NPs in vitro, although further studies, including in vivo studies and clinical trials, are needed to support our findings.