Abstract
Background: Curcumin has numerous properties and is used in many preclinical conditions, including cancer. It has low bioavailability, while its derivative EF24 shows enhanced solubility. However, its effects have never been explored in adrenocortical tumor cell models. The efficacy of EF24 alone or combined with mitotane (reference drug for adrenocortical cancer) was evaluated in two adrenocortical tumor cell lines, SW13 and H295R. Method and Results: EF24 reduced cell viability with an IC50 (half maximal inhibitory concentration) of 6.5 ± 2.4 μM and 4.9 ± 2.8 μM for SW13 and H295R cells, respectively. Combination index (EF24 associated with mitotane) suggested an additivity effect in both cell lines. Cell cycle analysis revealed an increase in subG0/G1 phase, while motility assay showed a decrease in migratory cell capacity, and similarly, clonogenic assay indicated that EF24 could reduce colony numbers. Furthermore, Wnt/β-catenin, NF-κB, MAPK, and PI3k/Akt pathways were modulated by Western blot analysis when treating cells with EF24 alone or combined with mitotane. In addition, intracellular reactive oxygen species levels increased in both cell lines. Conclusion: This work analyzed EF24 in adrenocortical tumor cell lines for the first time. These results suggest that EF24 could potentially impact on adrenocortical tumors, laying the foundation for further research in animal models.
Highlights
Adrenocortical tumors (ACT) are common diseases with a prevalence of 3–10% in the general population and can be categorized into adrenocortical adenomas (ACA), which is more frequent, and adrenocortical carcinoma (ACC), which is very rare and has an incidence of 1 to 2 per million per year [1]
By SRB assay we revealed that the IC50 of EF24 was 5.3 ± 2.7 μM and
In support of a potential role of EF24 in colony number reduction, the clonogenic assay showed that the compound could limit the stemness-like activity of tumor cell models (Figure 6), which is in line with previous studies on lung cancer cells [20]
Summary
Adrenocortical tumors (ACT) are common diseases with a prevalence of 3–10% in the general population and can be categorized into adrenocortical adenomas (ACA), which is more frequent, and adrenocortical carcinoma (ACC), which is very rare and has an incidence of 1 to 2 per million per year [1]. Curcumin has numerous properties and is used in many preclinical conditions, including cancer. It has low bioavailability, while its derivative EF24 shows enhanced solubility. The efficacy of EF24 alone or combined with mitotane (reference drug for adrenocortical cancer) was evaluated in two adrenocortical tumor cell lines, SW13 and H295R. Combination index (EF24 associated with mitotane) suggested an additivity effect in both cell lines. Conclusion: This work analyzed EF24 in adrenocortical tumor cell lines for the first time. These results suggest that EF24 could potentially impact on adrenocortical tumors, laying the foundation for further research in animal models
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