Evaluation of Antitumor Activity of Xanthones Conjugated with Amino Acids
Flávia Barbosa1, Joana Araújo2, Virgínia M F Gonçalves1,3
1UNIPRO-Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS-CESPU), 4585-116 Gandra, Portugal.
Abstract:
Cancer is a complex disease characterized by several alterations, which confer, to the cells, the capacity to proliferate uncontrollably and to resist cellular death. Multiresistance to conventional chemotherapy drugs is often the cause of treatment failure; thus, the search for natural products or their derivatives with therapeutic action is essential. Chiral derivatives of xanthones (CDXs) have shown potential inhibitory activity against the growth of some human tumor cell lines. This work reports the screening of a library of CDXs, through viability assays, in different cancer cell lines: A375-C5, MCF-7, NCI-H460, and HCT-15. CDXs' effect was analyzed based on several parameters of cancer cells, and it was also verified if these compounds were substrates of glycoprotein-P (Pgp), one of the main mechanisms of resistance in cancer therapy. Pgp expression was evaluated in all cell lines, but no expression was observed, except for HCT-15. Also, when a humanized yeast expressing the human gene MDR1 was used, no conclusions could be drawn about CDXs as Pgp substrates. The selected CDXs did not induce significant differences in the metabolic parameters analyzed. These results show that some CDXs present promising antitumor activity, but other mechanisms should be triggered by these compounds.
Insights
Chiral derivatives of xanthones (CDXs) show promising antitumor activity against various cancer cell lines. Further research is needed to understand the specific mechanisms driving their therapeutic effects.
Area of Science:
- Oncology
- Natural Product Chemistry
- Medicinal Chemistry
Background:
- Cancer cells exhibit uncontrolled proliferation and resistance to apoptosis, often leading to chemotherapy failure.
- Multidrug resistance in cancer necessitates the exploration of novel therapeutic agents, including natural product derivatives.
- Chiral derivatives of xanthones (CDXs) have emerged as potential candidates for cancer treatment due to observed inhibitory effects on tumor cell growth.
Purpose of the Study:
- To screen a library of CDXs for their potential antitumor activity against diverse human cancer cell lines.
- To evaluate the impact of CDXs on key cancer cell parameters, including viability and metabolic functions.
- To investigate whether CDXs are substrates of P-glycoprotein (Pgp), a major contributor to multidrug resistance.
Main Methods:
- Viability assays were performed on A375-C5, MCF-7, NCI-H460, and HCT-15 cancer cell lines.
- Cancer cell metabolic parameters were analyzed to assess the effects of CDX treatment.
- P-glycoprotein (Pgp) expression was evaluated in cell lines, and a humanized yeast model (MDR1) was used to test CDXs as Pgp substrates.
Main Results:
- Some CDXs demonstrated promising inhibitory activity against the tested cancer cell lines.
- No significant differences in metabolic parameters were induced by the selected CDXs.
- Pgp expression was detected only in the HCT-15 cell line; however, conclusive evidence regarding CDXs as Pgp substrates was not obtained.
Conclusions:
- Certain CDXs exhibit significant potential as antitumor agents, warranting further investigation.
- The therapeutic efficacy of these CDXs likely involves mechanisms beyond Pgp interaction.
- Additional research is required to elucidate the precise molecular pathways targeted by these promising compounds.
