TY  - EJOU
AU  - Pantazaka, Evangelia 
AU  - Papakonstantinou, Dimitrios 
AU  - Roumeliotou, Argyro 
AU  - Graikioti, Dafni 
AU  - Tsakas, Sotirios 
AU  - Zacharopoulou, Nefeli 
AU  - Martin, Stuart S. 
AU  - Kotsakis, Athanasios 
AU  - Athanassopoulos, Constantinos M. 
AU  - Alix-Panabières, Catherine 
AU  - Kallergi, Galatea 

TI  - Repurposing Artesunate to Combat Progression and Metastasis via Targeting Circulating Tumor Cells
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - <b>Objectives</b>: Circulating tumor cells (CTCs) drive metastasis and exhibit resistance to conventional therapies, making them crucial therapeutic targets. Artesunate (AS), a derivative of artemisinin, displays anticancer activity, including inhibition of JunB proto-oncogene (JUNB) and programmed death ligand-1 (PD-L1) and upregulation of Vimentin (VIM), markers related to poor prognosis in CTCs. This study aimed to evaluate the effects of AS on adherent and non-adherent cancer cell lines (breast, lung, colon), the patient-derived colon cancer CTC-MCC-41 line, and CTCs from small-cell lung cancer (SCLC) patients. <b>Methods</b>: AS’s effect was evaluated using TetherChip technology. Cell viability was measured using MTT assay, while immunofluorescence staining and the VyCAP platform were applied to characterize and quantify CTCs. <b>Results</b>: AS significantly reduces viability in all tested cell lines in a time- and concentration-dependent manner, with non-adherent cells showing higher resistance. Notably, CTC-MCC-41 cells are the most sensitive to AS treatment. AS demonstrates stronger cytotoxicity than 5-fluorouracil (5-FU) in most cancer models. In SCLC patient samples, AS reduces total CTC counts (<i>p</i> < 0.001), eliminates aggressive phenotypes such as (CK+/CXCR4+/JUNB–) and (CK+/VIM+/GLU+), and increases apoptotic (M30+) CTCs (<i>p</i> = 0.021). AS additionally impairs structural features like microtentacles, which facilitate CTC reattachment. <b>Conclusions</b>: These findings underscore AS’s ability to target metastasis-competent and anoikis-resistant tumor cells, reducing their viability, invasiveness, and survival mechanisms. AS emerges as a promising candidate for anti-metastatic therapy and warrants further investigation in precision oncology.
KW  - Artesunate; circulating tumor cells; anoikis; metastasis; small-cell lung cancer (SCLC); TetherChip; apoptosis

DO  - 10.32604/or.2026.075600