Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells
Abstract Background Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involv...
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| Format: | Article |
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BMC
2024-02-01
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| Series: | Genes and Environment |
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| Online Access: | https://doi.org/10.1186/s41021-023-00297-y |
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| author | Nur Syahirah Che Razali Kok Wai Lam Nor Fadilah Rajab A. Rahman A. Jamal Nurul Farahana Kamaludin Kok Meng Chan |
| author_facet | Nur Syahirah Che Razali Kok Wai Lam Nor Fadilah Rajab A. Rahman A. Jamal Nurul Farahana Kamaludin Kok Meng Chan |
| author_sort | Nur Syahirah Che Razali |
| collection | DOAJ |
| description | Abstract Background Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells. Results The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process. Conclusion The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells. |
| first_indexed | 2024-03-07T14:40:49Z |
| format | Article |
| id | doaj.art-6990a6906cfe4de2afd19b71f4a463bd |
| institution | Directory Open Access Journal |
| issn | 1880-7062 |
| language | English |
| last_indexed | 2024-03-07T14:40:49Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Genes and Environment |
| spelling | doaj.art-6990a6906cfe4de2afd19b71f4a463bd2024-03-05T20:22:29ZengBMCGenes and Environment1880-70622024-02-0146111610.1186/s41021-023-00297-yCurcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cellsNur Syahirah Che Razali0Kok Wai Lam1Nor Fadilah Rajab2A. Rahman A. Jamal3Nurul Farahana Kamaludin4Kok Meng Chan5Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan MalaysiaCentre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan MalaysiaCenter for Health Ageing and Wellness Studies, Faculty of Health Sciences, Universiti Kebangsaan MalaysiaUKM Medical Molecular Biology Institute, UKM Medical CentreCenter for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan MalaysiaCenter for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan MalaysiaAbstract Background Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells. Results The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process. Conclusion The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.https://doi.org/10.1186/s41021-023-00297-yGlioblastomaCurcuminoid analogueCurcuminApoptosisCaspaseMiRNA-21 |
| spellingShingle | Nur Syahirah Che Razali Kok Wai Lam Nor Fadilah Rajab A. Rahman A. Jamal Nurul Farahana Kamaludin Kok Meng Chan Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells Genes and Environment Glioblastoma Curcuminoid analogue Curcumin Apoptosis Caspase MiRNA-21 |
| title | Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells |
| title_full | Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells |
| title_fullStr | Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells |
| title_full_unstemmed | Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells |
| title_short | Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells |
| title_sort | curcumin piperidone derivatives induce caspase dependent apoptosis and suppress mirna 21 expression in ln 18 human glioblastoma cells |
| topic | Glioblastoma Curcuminoid analogue Curcumin Apoptosis Caspase MiRNA-21 |
| url | https://doi.org/10.1186/s41021-023-00297-y |
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