Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth
In this study, we propose lactucopicrin (LCTP), a natural sesquiterpene lactone from Lactucavirosa, as a molecule able to control the growth of glioblastoma continuous cell line U87Mg. The IC50 of U87Mg against LCTP revealed a strong cytotoxic effect. Daily administration of LCTP showed a dose and t...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/24/5843 |
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| author | Rossella Rotondo Maria Antonietta Oliva Sabrina Staffieri Salvatore Castaldo Felice Giangaspero Antonietta Arcella |
| author_facet | Rossella Rotondo Maria Antonietta Oliva Sabrina Staffieri Salvatore Castaldo Felice Giangaspero Antonietta Arcella |
| author_sort | Rossella Rotondo |
| collection | DOAJ |
| description | In this study, we propose lactucopicrin (LCTP), a natural sesquiterpene lactone from Lactucavirosa, as a molecule able to control the growth of glioblastoma continuous cell line U87Mg. The IC50 of U87Mg against LCTP revealed a strong cytotoxic effect. Daily administration of LCTP showed a dose and time-dependent reduction of GBM cell growth and viability, also confirmed by inhibition of clonogenic potential and mobility of U87Mg cells. LCTP activated autophagy in U87Mg cells and decreased the phosphorylation of proliferative signals pAKT and pERK. LCTP also induced the cell cycle arrest in G2/M phase, confirmed by decrease of CDK2 protein and increase of p53 and p21. LCTP stimulated apoptosis as evidenced by reduction of procaspase 6 and the increase of the cleaved/full-length PARP ratio. The pre-treatment of U87Mg cells with ROS scavenger N-acetylcysteine (NAC), which reversed its cytotoxic effect, showed the involvement of LCTP in oxidative stress. Finally, LCTP strongly enhanced the sensitivity of U87Mg cells to canonical therapy Temozolomide (TMZ) and synergized with this drug. Altogether, the growth inhibition of U87Mg GBM cells induced by LCTP is the result of several synergic mechanisms, which makes LCTP a promising adjuvant therapy for this complex pathology. |
| first_indexed | 2024-03-10T14:09:28Z |
| format | Article |
| id | doaj.art-23f0b43eedce4e2cab016dee8536b2f1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:09:28Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-23f0b43eedce4e2cab016dee8536b2f12023-11-21T00:16:42ZengMDPI AGMolecules1420-30492020-12-012524584310.3390/molecules25245843Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell GrowthRossella Rotondo0Maria Antonietta Oliva1Sabrina Staffieri2Salvatore Castaldo3Felice Giangaspero4Antonietta Arcella5Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, ItalyI.R.C.C.S Neuromed, Via Atinense, 18, 86077 Pozzilli IS, ItalyI.R.C.C.S Neuromed, Via Atinense, 18, 86077 Pozzilli IS, ItalyI.R.C.C.S Neuromed, Via Atinense, 18, 86077 Pozzilli IS, ItalyI.R.C.C.S Neuromed, Via Atinense, 18, 86077 Pozzilli IS, ItalyI.R.C.C.S Neuromed, Via Atinense, 18, 86077 Pozzilli IS, ItalyIn this study, we propose lactucopicrin (LCTP), a natural sesquiterpene lactone from Lactucavirosa, as a molecule able to control the growth of glioblastoma continuous cell line U87Mg. The IC50 of U87Mg against LCTP revealed a strong cytotoxic effect. Daily administration of LCTP showed a dose and time-dependent reduction of GBM cell growth and viability, also confirmed by inhibition of clonogenic potential and mobility of U87Mg cells. LCTP activated autophagy in U87Mg cells and decreased the phosphorylation of proliferative signals pAKT and pERK. LCTP also induced the cell cycle arrest in G2/M phase, confirmed by decrease of CDK2 protein and increase of p53 and p21. LCTP stimulated apoptosis as evidenced by reduction of procaspase 6 and the increase of the cleaved/full-length PARP ratio. The pre-treatment of U87Mg cells with ROS scavenger N-acetylcysteine (NAC), which reversed its cytotoxic effect, showed the involvement of LCTP in oxidative stress. Finally, LCTP strongly enhanced the sensitivity of U87Mg cells to canonical therapy Temozolomide (TMZ) and synergized with this drug. Altogether, the growth inhibition of U87Mg GBM cells induced by LCTP is the result of several synergic mechanisms, which makes LCTP a promising adjuvant therapy for this complex pathology.https://www.mdpi.com/1420-3049/25/24/5843glioblastoma (GBM)lactucopicrin (LCTP)temozolomide (TMZ)autophagyoxidative stressNF-κB |
| spellingShingle | Rossella Rotondo Maria Antonietta Oliva Sabrina Staffieri Salvatore Castaldo Felice Giangaspero Antonietta Arcella Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth Molecules glioblastoma (GBM) lactucopicrin (LCTP) temozolomide (TMZ) autophagy oxidative stress NF-κB |
| title | Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth |
| title_full | Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth |
| title_fullStr | Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth |
| title_full_unstemmed | Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth |
| title_short | Implication of Lactucopicrin in Autophagy, Cell Cycle Arrest and Oxidative Stress to Inhibit U87Mg Glioblastoma Cell Growth |
| title_sort | implication of lactucopicrin in autophagy cell cycle arrest and oxidative stress to inhibit u87mg glioblastoma cell growth |
| topic | glioblastoma (GBM) lactucopicrin (LCTP) temozolomide (TMZ) autophagy oxidative stress NF-κB |
| url | https://www.mdpi.com/1420-3049/25/24/5843 |
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