TY  - JOUR
T1  - A Ruthenium-5-Fluorouracil Coordination Complex Induces Apoptosis and Autophagy While Suppressing Stemness in Colorectal Cancer Cells via Akt/mTOR Inhibition
A1  - Robert Ian Campbell
A1  - David Scott Wilson
A1  - Pieter Jan Verhoeven
A1  - Koen Maarten Peeters
A1  - Sarah Jane Collins
JF  - Archive of International Journal of Cancer and Allied Science
JO  - Arch Int J Cancer Allied Sci
SN  - 3108-4834
Y1  - 2025
VL  - 5
IS  - 1
DO  - 10.51847/iqrmviP98D
SP  - 200
EP  - 216
N2  - [Ru(5-FU)(PPh3)2(bipy)]PF6 (Ru/5-FU) is a newly developed ruthenium-based complex incorporating 5-fluorouracil, showing notable activity against colorectal cancer (CRC). In this study, we examined the molecular effects of Ru/5-FU in HCT116 CRC cells. Ru/5-FU demonstrated strong cytotoxic effects across multiple cancer cell types, including primary tumor cells, and triggered apoptosis in HCT116 cells. Treatment with Ru/5-FU lowered AKT1 mRNA levels and suppressed the expression of Akt1, phosphorylated Akt (pS473), and downstream effectors mTOR (pS2448), S6 (pS235/pS236), 4EBP1 (pT36/pT45), GSK-3β (pS9), and NF-κB p65 (pS529), without altering upstream regulators Hsp90 and PI3K p85/p55 (pT458/pT199), suggesting inhibition of Akt/mTOR signaling. Ru/5-FU also promoted LC3B accumulation and decreased p62/SQSTM1, indicating autophagy activation. Interestingly, blocking autophagy with 3-methyladenine or chloroquine enhanced Ru/5-FU cytotoxicity, suggesting autophagy has a protective role. Ru/5-FU reduced colony formation, decreased CD133+ populations, and impaired colonosphere formation, demonstrating suppression of cancer stem-like cells. Moreover, Ru/5-FU inhibited migration and invasion, coinciding with decreased vimentin and increased E-cadherin levels, pointing to disruption of epithelial-mesenchymal transition. In vivo, Ru/5-FU suppressed HCT116 tumor growth and lung metastasis in mouse xenografts. Collectively, these data indicate that Ru/5-FU may serve as an effective anti-CRC agent capable of targeting cancer stemness via Akt/mTOR inhibition.
UR  - https://smerpub.com/article/a-ruthenium-5-fluorouracil-coordination-complex-induces-apoptosis-and-autophagy-while-suppressing-st-ccy384oflz7rjef
ER  -