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

  • Sci Rep. 2022 Jul 30;12(1):13131. doi: 10.1038/s41598-022-16274-4.
Nur Syahirah Che Razali  1 ,  Kok Wai Lam  2 ,  Nor Fadilah Rajab  3 ,  A Rahman A Jamal  4 ,  Nurul Farahana Kamaluddin  1 ,  Kok Meng Chan  5  6
Affiliations
  • 1. Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia.
  • 2. Center for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia.
  • 3. Center for Healthy Ageing and Wellness, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia.
  • 4. UKM Medical Molecular Biology Institute, UKM Medical Centre, 56000, Cheras, Malaysia.
  • 5. Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300, Kuala Lumpur, Malaysia. [email protected].
  • 6. Institute for Environmental and Development, UKM, 43600, Bangi, Selangor, Malaysia. [email protected].
PMID: 35907913 DOI: 10.1038/s41598-022-16274-4
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 IC50 values of 2.5 µM and 4 µM respectively, which were more potent compared to curcumin with IC50 of 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.

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