Ferrocifen derivatives that induce senescence in cancer cells: selected examples

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Metallodrugs

Background:

• Platinum coordination complexes are established anti-tumor agents.
• Limitations of platinum drugs necessitate research into novel metallodrugs with alternative mechanisms.
• Ferrocenyl complexes offer a promising avenue for developing new anti-cancer therapies.

Purpose of the Study:

• To evaluate the anti-cancer potential of two novel ferrocenyl complexes, P5 and DP1.
• To investigate the mechanism of action, including senescence induction, of these complexes in cancer cell models.
• To assess the efficacy of P5 and DP1 against chemoresistant cancer types.

Main Methods:

• Assay of P5 and DP1 in various cancer cell models (glioma, melanoma, pluripotent stem-like cells).
• Assessment of growth inhibitory effects and determination of IC50 values.
• Analysis of senescence induction via SA-β-galactosidase staining and senescence-associated secretory phenotype (SASP) markers (IL-1α, IL-1β, IL-6, IL-8, TNF-α).
• In vivo studies using B16F10 melanoma cell grafts in mice.

Main Results:

• P5 and DP1 exhibited significant growth inhibitory effects (0.5-10 μM) against tested cancer cells.
• Senescence induction, characterized by SA-β-galactosidase staining and SASP, was observed.
• Cytokine secretion regulation was potentially linked to AP-1 and other transcription factors.
• Pre-incubation with P5 or DP1 enhanced survival in mice bearing B16F10 tumors.

Conclusions:

• P5 and DP1 ferrocenyl complexes demonstrate potent anti-cancer activity.
• These complexes induce senescence in diverse cancer cell models, including those with varying pro-apoptotic sensitivity.
• Ferrocenyl complexes represent a promising class of metallodrugs for overcoming chemoresistance.