Studies on the effect of curcumin and its glucoside derivatives on IMR-32 neuroblastoma cell lines.

Abstract

Background: The hallmark pathologies of neurodegenerative diseases include neuroinflammation, oxidative stress, mitochondrial dysfunction, protein misfolding, and dysregulated cell-survival signaling. These biochemical processes lead to neuronal death in disorders such as Alzheimer's disease, Parkinson's disease, and others. The complexities involved in neuronal cell death still need to be unraveled.

Objective: To study the role of curcumin and its mono- and diglucoside derivatives in IMR32 cells, focused on cytotoxicity, cell cycle analysis, apoptosis, reactive oxygen species (ROS), antioxidant potential, 8-hydroxy-guanosine (8-OH-G)* production, and cell and nuclear morphology.

Methods: In the present study, we synthesized a novel molecule, curcumin mono- and diglucoside, to improve the water solubility and partition coefficient, making the molecule highly bioavailable. We assessed cytotoxicity using the MTT assay and trypan blue, with a Nikon Eclipse E200 microscope. cell cycle and apoptosis by FACS, cell morphology by a Nikon microscope, nuclear morphology by confocal imaging, and 8-OH-G*, ROS, and antioxidant activity by ELISA kits.

Results: Our findings show that (1) curcumin and the positive control compound doxorubicin have lower IC₅₀ values than curcumin monoglucoside and diglucoside; (2) The three compounds induce distinct cell-cycle arrests (curcumin: S-phase; curcumin-monoglucoside: G0-G1; curcumin diglucoside: G2). Curc-glucoside also reduced ROS production and DNA damage marker 8-OH-G*, while activating antioxidant potential; (3) Curcumin mainly causes necrosis; Curcumin mono- and diglucosides did not induce any apoptosis or necrosis; and doxorubicin promotes apoptosis only.

Conclusions: Curcumin mono- and diglucoside efficiently reduced ROS, increased antioxidant activity, and decreased 8-OH-G* production. Curcumin is more prooxidant and proapoptotic, whereas glycosylated derivatives are more antioxidant and cytostatic.