Molecular Mechanism of Action of 2‐Ferrocenyl‐1,1‐diphenylbut‐1‐ene on HL‐60 Leukemia Cells

Abstract

The aim of this work was to investigate the mechanism of action of 2-ferrocenyl-1,1-diphenylbut-1-ene (1) on HL-60 human leukemia cells. While inactive against noncancerous cells, 1 provoked a concentration-dependent decrease in viable tumor cells, primarily via apoptosis, as evidenced by analysis of cell morphology, activation of caspases 3 and 7, increased DNA fragmentation, and externalization of phosphatidylserine. Necrosis was observed only at the highest tested concentration (4 μM). Compound 1 interfered with the cell cycle, causing an accumulation of cells in the G1 /G0 phase. Interaction of 1 with dsDNA and ssDNA was observed by differential pulse voltammetry and confirmed by hyperchromicity in the UV/Vis spectra of dsDNA, with an interaction constant of 2×10(4) M(-1). Both the organic analogue 1,1,2-triphenylbut-1-ene (2) and ferrocene were inactive against cancer and noncancer cell lines and did not react with DNA. These results reinforce the idea that the hybrid strategy of conjugating ferrocene to the structure of tamoxifen derivatives is advantageous in finding new substances with antineoplastic activity.

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

“…Indeed, Ru-arene complexes have been designed to interact with DNA by intercalation and methylation ( Aird et al 2002) . Despite no DNA-interaction studies were performed with the ruthenocifens presented herein, a recent report ( de Oliveira et al 2014) proved, by performing differential pulse voltammetry and spectrophotometric analysis, the interaction of compound 3 with double-stranded DNA and single-stranded DNA.…”

Ferrocifen type anti cancer drugs

“…This complex induces apoptosis with an accumulation of cells in the G0/G1 phase and is followed by fragmentation of DNA, a result based on phosphatidylserine externalisation and increase of caspases 3 et 7. 58…”

“…This complex has an elevated cytotoxicity on the leukemia cells HL-60 (IC 50 = 1.04 µM) but a more modest one on MDA-MB-231 cells (IC 50 = 7.5 µM). At a concentration of 1 µM it induces apoptosis of HL-60 with an accumulation of cells in the G0/G1 phase 58. This singular behaviour is probably associated with the production of ROS (see below).…”

Scope of organometallic compounds based on transition metal-arene systems as anticancer agents: starting from the classical paradigm to targeting multiple strategies

“…The ferrocifens exhibited highly promising antiproliferative activity towards breast cancer due to the redox behavior of iron. [210][211][212] Thus, A. C. de Oliveira et al 213 The effectiveness of the available chemotherapeutic drugs is still limited due to the intrinsic resistance inside cancer cells. This intrinsic resistance can be overcome via the use of organometallic redox active complexes such as ferrocene, which are into an inactive indene in protic medium.…”