Curcumin piperidone derivatives induce anti-proliferative and anti-migratory effects in LN-18 human glioblastoma cells.

in Scientific reports by Nur Syahirah Che Razali, Kok Wai Lam, Nor Fadilah Rajab, A Rahman A Jamal, Nurul Farahana Kamaluddin, Kok Meng Chan

TLDR

  • Researchers synthesized curcuminoid analogues to improve upon the limitations of curcumin's bioavailability and metabolism, and found they exhibited potent anti-cancer properties against glioblastoma cells.
  • The analogues showed concentration-dependent cytotoxicity, induced oxidative stress, and inhibited cell migration and invasion.

Abstract

Curcumin has demonstrated potential cytotoxicity across various cell lines despite its poor bioavailability and rapid metabolism. Therefore, our group have synthesized curcuminoid analogues with piperidone derivatives, FLDP-5 and FLDP-8 to overcome these limitations. In this study, the analogues were assessed on LN-18 human glioblastoma cells in comparison to curcumin. Results from cytotoxicity assessment showed that FLDP-5 and FLDP-8 curcuminoid analogues caused death in LN-18 cells in a concentration-dependent manner after 24-h treatment with much lower ICvalues of 2.5 µM and 4 µM respectively, which were more potent compared to curcumin with ICof 31 µM. Moreover, a significant increase (p < 0.05) in the level of superoxide anion and hydrogen peroxide upon 2-h and 6-h treatment confirmed the oxidative stress involvement in the cell death process induced by these analogues. These analogues also showed potent anti-migratory effects through inhibition of LN-18 cells' migration and invasion. In addition, cell cycle analysis showed that these analogues are capable of inducing significant (p < 0.05) S-phase cell cycle arrest during the 24-h treatment as compared to untreated, which explained the reduced proliferation indicated by MTT assay. In conclusion, these curcuminoid analogues exhibit potent anti-cancer effects with anti-proliferative and anti-migratory properties towards LN-18 cells as compared to curcumin.

Overview

  • The study synthesized curcuminoid analogues, FLDP-5 and FLDP-8, to overcome the limitations of curcumin's poor bioavailability and rapid metabolism.
  • The analogues were assessed on LN-18 human glioblastoma cells in comparison to curcumin for their cytotoxicity and anti-migratory properties.
  • The primary objective was to evaluate the potential of these analogues as anti-cancer agents and compare their effects to those of curcumin.

Comparative Analysis & Findings

  • FLDP-5 and FLDP-8 showed concentration-dependent cytotoxicity in LN-18 cells, with lower IC values (2.5 µM and 4 µM respectively) compared to curcumin (31 µM).
  • The analogues induced significant oxidative stress, as measured by increases in superoxide anion and hydrogen peroxide levels, and caused cell cycle arrest in the S-phase.
  • The analogues exhibited potent anti-migratory effects, inhibiting LN-18 cell migration and invasion, and showed reduced proliferation compared to untreated cells.

Implications and Future Directions

  • These curcuminoid analogues may be useful as potential anti-cancer agents, particularly in glioblastoma treatment, due to their potent anti-proliferative and anti-migratory properties.
  • Further studies are required to evaluate the efficacy and safety of these analogues in preclinical and clinical settings.
  • Mechanistic studies should be conducted to understand the underlying mechanisms of anti-cancer activity and oxidative stress induction by these analogues.
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