An in vitro comparative study with furyl-1,4-quinones endowed with anticancer activities
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Published on: June 26, 2018
Julio Benites1, Jaime A Valderrama, Henryk Taper
1Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat, Iquique, Chile, Avenida Arturo Prat 2120, Casilla 121, Iquique, Chile.
Abstract:
We describe the biological activity of some furylbenzo- and naphthoquinones (furylquinones) on hepatocarcinoma cells and healthy rat liver slices. The effects of furylquinones on cancer cells (Transplantable Liver Tumor, TLT) were assessed by measuring cell death (membrane cell lysis); intracellular contents of ATP and GSH and the activity of caspase-3 were used to determine the type of cell death. Most of the furylquinones tested (at a concentration of 25 μg/ml) induced caspase-independent cell death but compound 4 had no cytotoxic effects. The levels of both ATP and GSH were severely affected by quinones 1, 2 and 5, while no effect was observed with compound 4. These cytotoxic properties of quinones are associated with physico-chemical properties as shown by the LUMO energies and lipophilicity. Interestingly, no cytotoxic effects of furylquinones were detected when the in vitro model of precision-cut liver slices (PCLS) was used. Indeed, although CYP2E1 activity was slightly affected, ATP and GSH levels as well as protein synthesis were not modified by furylquinones. Paracetamol, a well-known hepatotoxicant, reduced these parameters by more than 80% compared to control conditions. Taking into account the considerable incidence of adverse-effects induced by most current anticancer drugs, the selective cytotoxicity shown by compounds 1, 2 and 5, in particular that of 1, represents a safety factor that encourages the further development of these quinones as new drugs in cancer therapy.
Insights
Furylquinones show selective anticancer activity against liver cancer cells, inducing cell death without harming healthy liver cells. This suggests potential for developing safer cancer therapies.
Area of Science:
- Medicinal Chemistry
- Hepatology
- Cancer Biology
Background:
- Hepatocellular carcinoma (HCC) remains a significant health challenge.
- Current anticancer drugs often exhibit severe side effects.
- Novel therapeutic agents with improved safety profiles are needed.
Purpose of the Study:
- To evaluate the biological activity of furylbenzo- and naphthoquinones (furylquinones) against hepatocarcinoma cells.
- To assess the safety and cytotoxicity of furylquinones on healthy liver tissue.
- To explore the potential of furylquinones as novel anticancer drugs.
Main Methods:
- In vitro assessment of furylquinones on Transplantable Liver Tumor (TLT) cells and precision-cut liver slices (PCLS).
- Measurement of cell death (membrane lysis), intracellular ATP and GSH levels, and caspase-3 activity.
- Correlation of cytotoxic properties with physicochemical parameters like LUMO energies and lipophilicity.
Main Results:
- Most tested furylquinones induced caspase-independent cell death in TLT cells.
- Compounds 1, 2, and 5 significantly affected ATP and GSH levels in cancer cells.
- No cytotoxic effects were observed in PCLS, with minimal impact on CYP2E1 activity, ATP, GSH, or protein synthesis.
- Compound 4 exhibited no cytotoxic effects on either cell type.
Conclusions:
- Furylquinones, particularly compounds 1, 2, and 5, demonstrate selective cytotoxicity against liver cancer cells.
- The lack of toxicity in healthy liver cells suggests a favorable safety profile.
- These findings support the further development of furylquinones as potential anticancer therapeutics.
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