A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development
Khat (<i>Catha edulis (Vahl) Forssk. ex Endl</i>.) is habitually used as a natural stimulant by millions of people, but is associated with adverse effects on gastrointestinal, cardiovascular and central neural systems. At the cellular level khat toxicity involves p53 induction and cell c...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/12/3596 |
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| author | Therese Bredholt Onyango Sigrun M. Hjelle Ingvild Haaland Olav K. Vintermyr Anne Christine Johannessen Bjørn Tore Gjertsen |
| author_facet | Therese Bredholt Onyango Sigrun M. Hjelle Ingvild Haaland Olav K. Vintermyr Anne Christine Johannessen Bjørn Tore Gjertsen |
| author_sort | Therese Bredholt Onyango |
| collection | DOAJ |
| description | Khat (<i>Catha edulis (Vahl) Forssk. ex Endl</i>.) is habitually used as a natural stimulant by millions of people, but is associated with adverse effects on gastrointestinal, cardiovascular and central neural systems. At the cellular level khat toxicity involves p53 induction and cell cycle arrest, decreased mitochondrial function and activation of receptor- and mitochondria-mediated cell death pathways. In this study we have examined an extract of khat for induction of p53 post-translational modifications (PTMs) and the functional role of p53 in khat-mediated cell death. Khat was shown to induce phosphorylation and acetylation of p53 in both the khat-sensitive MOLM-13 and the khat-resistant MV-4-11 cell line, but accumulation of the full-length p53 isoform was only observed in the khat sensitive cell line. Small molecule inhibitors of p38 MAP kinase sensitized MV-4-11 cells for khat-treatment without concomitant stabilization of p53. Experiments using a p53 knock-down cell line and murine p53 knock-out bone marrow cells indicated that p53 was redundant in khat-mediated cell death in vitro. We suggest that analysis of isoform patterns and p53 PTMs are useful for elucidation of biological effects of complex plant extracts, and that p53 protein analysis is particularly useful in the search for new chemical probes and experimental cancer therapeutics. |
| first_indexed | 2024-03-10T14:24:02Z |
| format | Article |
| id | doaj.art-2df48c2fcd384a63a52d05555af9ba76 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:24:02Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2df48c2fcd384a63a52d05555af9ba762023-11-20T23:06:01ZengMDPI AGCancers2072-66942020-12-011212359610.3390/cancers12123596A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy DevelopmentTherese Bredholt Onyango0Sigrun M. Hjelle1Ingvild Haaland2Olav K. Vintermyr3Anne Christine Johannessen4Bjørn Tore Gjertsen5Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, N-5021 Bergen, NorwayCentre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, N-5021 Bergen, NorwayCentre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, N-5021 Bergen, NorwayDepartment of Pathology, Haukeland University Hospital, N-5021 Bergen, NorwayDepartment of Pathology, Haukeland University Hospital, N-5021 Bergen, NorwayCentre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, N-5021 Bergen, NorwayKhat (<i>Catha edulis (Vahl) Forssk. ex Endl</i>.) is habitually used as a natural stimulant by millions of people, but is associated with adverse effects on gastrointestinal, cardiovascular and central neural systems. At the cellular level khat toxicity involves p53 induction and cell cycle arrest, decreased mitochondrial function and activation of receptor- and mitochondria-mediated cell death pathways. In this study we have examined an extract of khat for induction of p53 post-translational modifications (PTMs) and the functional role of p53 in khat-mediated cell death. Khat was shown to induce phosphorylation and acetylation of p53 in both the khat-sensitive MOLM-13 and the khat-resistant MV-4-11 cell line, but accumulation of the full-length p53 isoform was only observed in the khat sensitive cell line. Small molecule inhibitors of p38 MAP kinase sensitized MV-4-11 cells for khat-treatment without concomitant stabilization of p53. Experiments using a p53 knock-down cell line and murine p53 knock-out bone marrow cells indicated that p53 was redundant in khat-mediated cell death in vitro. We suggest that analysis of isoform patterns and p53 PTMs are useful for elucidation of biological effects of complex plant extracts, and that p53 protein analysis is particularly useful in the search for new chemical probes and experimental cancer therapeutics.https://www.mdpi.com/2072-6694/12/12/3596p53 isoformsPTMsCPTkhat |
| spellingShingle | Therese Bredholt Onyango Sigrun M. Hjelle Ingvild Haaland Olav K. Vintermyr Anne Christine Johannessen Bjørn Tore Gjertsen A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development Cancers p53 isoforms PTMs CPT khat |
| title | A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development |
| title_full | A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development |
| title_fullStr | A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development |
| title_full_unstemmed | A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development |
| title_short | A Comparison of p53 Isoform Profiles and Apoptosis Induced by Camptothecin or a Herbal Khat Extract (<i>Catha Edulis (Vahl) Forssk. ex Endl.</i>) in Leukemic Cell Lines: Exploring Cellular Responses in Therapy Development |
| title_sort | comparison of p53 isoform profiles and apoptosis induced by camptothecin or a herbal khat extract i catha edulis vahl forssk ex endl i in leukemic cell lines exploring cellular responses in therapy development |
| topic | p53 isoforms PTMs CPT khat |
| url | https://www.mdpi.com/2072-6694/12/12/3596 |
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