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Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster
Camptothecin (CPT), first isolated from Chinese tree Camptotheca acuminate, produces rapid and prolonged inhibition of DNA synthesis and induction of DNA damage by targeting topoisomerase I (top1), which is highly activated in cancer cells. CPT thus exhibits remarkable anticancer activities in vario...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864452/ https://www.ncbi.nlm.nih.gov/pubmed/36675143 http://dx.doi.org/10.3390/ijms24021617 |
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author | Zhang, Jing Zhang, Shijie Sun, Zhipeng Cai, Yu Zhong, Guohua Yi, Xin |
author_facet | Zhang, Jing Zhang, Shijie Sun, Zhipeng Cai, Yu Zhong, Guohua Yi, Xin |
author_sort | Zhang, Jing |
collection | PubMed |
description | Camptothecin (CPT), first isolated from Chinese tree Camptotheca acuminate, produces rapid and prolonged inhibition of DNA synthesis and induction of DNA damage by targeting topoisomerase I (top1), which is highly activated in cancer cells. CPT thus exhibits remarkable anticancer activities in various cancer types, and is a promising therapeutic agent for the treatment of cancers. However, it remains to be uncovered underlying its cytotoxicity toward germ cells. In this study we found that CPT, a cell cycle-specific anticancer agent, reduced fecundity and exhibited significant cytotoxicity toward GSCs and two-cell cysts. We showed that CPT induced GSC loss and retarded two-cell cysts differentiation in a niche- or apoptosis-independent manner. Instead, CPT induced ectopic expression of a differentiation factor, bag of marbles (Bam), and regulated the expression of cyclin A, which contributed to GSC loss. In addition, CPT compromised two-cell cysts differentiation by decreasing the expression of Bam and inducing cell arrest at G1/S phase via cyclin A, eventually resulting in two-cell accumulation. Collectively, this study demonstrates, for the first time in vivo, that the Bam–cyclin A axis is involved in CPT-mediated germline stem cell loss and two-cell cysts differentiation defects via inducing cell cycle arrest, which could provide information underlying toxicological effects of CPT in the productive system, and feature its potential to develop as a pharmacology-based germline stem cell regulation agent. |
format | Online Article Text |
id | pubmed-9864452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98644522023-01-22 Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster Zhang, Jing Zhang, Shijie Sun, Zhipeng Cai, Yu Zhong, Guohua Yi, Xin Int J Mol Sci Article Camptothecin (CPT), first isolated from Chinese tree Camptotheca acuminate, produces rapid and prolonged inhibition of DNA synthesis and induction of DNA damage by targeting topoisomerase I (top1), which is highly activated in cancer cells. CPT thus exhibits remarkable anticancer activities in various cancer types, and is a promising therapeutic agent for the treatment of cancers. However, it remains to be uncovered underlying its cytotoxicity toward germ cells. In this study we found that CPT, a cell cycle-specific anticancer agent, reduced fecundity and exhibited significant cytotoxicity toward GSCs and two-cell cysts. We showed that CPT induced GSC loss and retarded two-cell cysts differentiation in a niche- or apoptosis-independent manner. Instead, CPT induced ectopic expression of a differentiation factor, bag of marbles (Bam), and regulated the expression of cyclin A, which contributed to GSC loss. In addition, CPT compromised two-cell cysts differentiation by decreasing the expression of Bam and inducing cell arrest at G1/S phase via cyclin A, eventually resulting in two-cell accumulation. Collectively, this study demonstrates, for the first time in vivo, that the Bam–cyclin A axis is involved in CPT-mediated germline stem cell loss and two-cell cysts differentiation defects via inducing cell cycle arrest, which could provide information underlying toxicological effects of CPT in the productive system, and feature its potential to develop as a pharmacology-based germline stem cell regulation agent. MDPI 2023-01-13 /pmc/articles/PMC9864452/ /pubmed/36675143 http://dx.doi.org/10.3390/ijms24021617 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Zhang, Jing Zhang, Shijie Sun, Zhipeng Cai, Yu Zhong, Guohua Yi, Xin Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster |
title | Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster |
title_full | Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster |
title_fullStr | Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster |
title_full_unstemmed | Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster |
title_short | Camptothecin Effectively Regulates Germline Differentiation through Bam–Cyclin A Axis in Drosophila melanogaster |
title_sort | camptothecin effectively regulates germline differentiation through bam–cyclin a axis in drosophila melanogaster |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864452/ https://www.ncbi.nlm.nih.gov/pubmed/36675143 http://dx.doi.org/10.3390/ijms24021617 |
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