Abstract
Camptothecin (CPT) and CPT-derived drugs are widely used against gynaecological and colorectal cancers. On account of their mechanism of action these drugs target rapidly dividing cells and may have an adverse effect on normal tissues. We sought to investigate their impact on normal cells by using Drosophila as a model. We investigated the possible involvement of Drosophila homologue of p53 (Dmp53) and a member of the retinoblastoma binding protein 6 family, known as Snama. On account of its molecular features and experimental evidence gleaned from mammalian studies we propose Snama as a candidate in Dmp53 regulation. We have used proteomics and core molecular biology techniques on embryos and on adult flies. We found that flies that recover from CPT treatment display a metabolic programme characterized by glycolytic flux, depletion of Dmp53 and increase of Snama transcripts. When we introduced methyl pyruvate in the diet to bypass the glycolytic pathway, we noticed differential expression of Dmp53 and Snama and improvement in reproduction and embryonic development. The development of embryos into the pupal stage was significantly improved to 40% (P=0.02) when CPT was given to mothers in combination with methyl pyruvate. This investigation highlights the importance of energy production mechanisms in cells that recover from chemotherapy and differences between the metabolic programmes used by recovering cells and those adopted by cancer cells.
