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Published on: April 26, 2018
In vitro evaluation of cytotoxic and mutagenic activity of avarol
Boris Pejin1,2, Carmine Iodice1, Vesna Kojic3
1a National Research Council of Italy, Institute of Biomolecular Chemistry, CNR-ICB , Pozzuoli-Naples , Italy.
Abstract:
The cytotoxicity of avarol, a main secondary metabolite of the Mediterranean sponge Dysidea avara, was in vitro screened by MTT assay against four human tumour cell lines. The colon HT-29 tumour cells practically showed to be the only sensitive ones towards this organic compound. No toxicity was found against the fetal lung fibroblast MRC-5 cells at the concentrations tested. In comparison with doxorubicin, used as a positive control, avarol actually exhibited at least 588-fold less toxicity towards normal MRC-5 cells. Finally, comet assay indicated that DNA fragmentation was almost fivefold higher upon the treatment with doxorubicin, compared to avarol. The obtained results have actually confirmed that avarol scaffold may contribute to development of new cytostatics inspired by nature.
Insights
Avarol, a sponge compound, shows selective toxicity against colon cancer cells. It is significantly less toxic to normal cells than doxorubicin, suggesting potential for new cancer drug development.
Area of Science:
- Marine natural products chemistry
- Cancer biology
- Drug discovery
Background:
- Avarol is a secondary metabolite from the Dysidea avara sponge.
- Natural products are a source of novel therapeutic agents.
- Understanding avarol's cytotoxicity is crucial for drug development.
Purpose of the Study:
- To evaluate the in vitro cytotoxicity of avarol against human tumor cell lines.
- To compare avarol's toxicity to normal cells with a standard chemotherapy drug.
- To investigate avarol's effect on DNA integrity.
Main Methods:
- Cytotoxicity screening using MTT assay.
- Testing against four human tumor cell lines (including HT-29).
- Assessment of toxicity against normal human fetal lung fibroblast MRC-5 cells.
- Comet assay to evaluate DNA fragmentation.
Main Results:
- Avarol demonstrated selective cytotoxicity, primarily affecting HT-29 colon tumor cells.
- No significant toxicity was observed in normal MRC-5 cells at tested concentrations.
- Avarol exhibited 588-fold less toxicity towards normal cells compared to doxorubicin.
- DNA fragmentation was significantly lower with avarol treatment than with doxorubicin.
Conclusions:
- The avarol scaffold shows promise for developing new nature-inspired cytostatic drugs.
- Avarol presents a favorable safety profile compared to doxorubicin.
- Further research into avarol derivatives could lead to novel cancer therapeutics.
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