PUBLICATION
Zebrafish embryonic development-interfering macrolides from Streptomyces californicus impact growth and mitochondrial function in human colorectal cancer cells
- Authors
- Tan, P. J., Lau, B. F., Krishnasamy, G., Ng, M. F., Husin, L. S., Ruslan, N., Song, D. S.S., Velaithan, V., Okuda, K. S., and Patel, V.
- ID
- ZDB-PUB-181108-9
- Date
- 2018
- Source
- Process Biochemistry 74: 164-174 (Journal)
- Registered Authors
- Okuda, Kazuhide Shaun
- Keywords
- Actinobacteria, Macrolides, Mitochondria, Streptomyces, Zebrafish
- MeSH Terms
- none
- PubMed
- none Full text @ Proc. Biochemistry
Citation
Tan, P. J., Lau, B. F., Krishnasamy, G., Ng, M. F., Husin, L. S., Ruslan, N., Song, D. S.S., Velaithan, V., Okuda, K. S., and Patel, V. (2018) Zebrafish embryonic development-interfering macrolides from Streptomyces californicus impact growth and mitochondrial function in human colorectal cancer cells. Process Biochemistry. 74:164-174.
Abstract
Microorganisms are now recognized as a keysource of medicine. In this study, we aim to identify and characterize target-specific inhibitors from actinobacteria using zebrafish embryo developmental defect as readouts. From our preliminary screen, we evaluated 176 Malaysian actinobacteria extracts and from these, 15 extracts (8.52%) were observed to be toxic to embryos at 20 μg/mL at 72-h post fertilization (hpf). Detailed characterization of these 15 toxic hits uncovered one extract derived from Streptomyces californicus TY004-069 that arrested zebrafish embryonic development at 4–6 hpf after 24 h treatment, a phenotype indicative potentially targeting mitochondrial activity. Subsequent validation on one of the three isolated compounds from this extract, dimeric dinactin (DD) revealed its ability to disrupt mitochondrial membrane potential (MMP) in human colorectal HCT116 and HT29 cancer cells in a dose-dependent manner and impacting cell proliferation through a cell cycle G block. Overall, using zebrafish phenotypic assay, we identified a potential mitochondrial function inhibitor from actinobacteria that warrants further detailed analysis and also demonstrated that macrolides may hold promise as therapeutic molecules for human diseases including cancer.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping