The Effect of a Ferrocene Containing Camphor Sulfonamide DK-164 on Breast Cancer Cell Lines

Abstract

Background: Drug resistance is a major cause of cancer treatment failure. Most cancer therapies involve multiple agents, to overcome it. Compounds that exhibit strong anti-tumor effect without damaging normal cells are more and more in the focus of research. Chemotherapeutic drugs, combining different moieties and functional groups in one molecule, can modulate different regulatory pathways in the cell and thus reach the higher efficacy than the agents, which affect only one cellular process. Methods: We tested the effect of recently synthesized ferrocene-containing camphor sulfonamide DK-164 on two breast cancer and one breast non-cancer cell lines. The cytotoxic effects were evaluated using the standard MTT-dye reduction and clonogenic assays. The apoptotic or autophagic effects were evaluated by Annexin v binding or LC3 puncta formation assays respectively. Cell cycle arrest was determined using flow cytometry. Western blot and immunofluorescent analyses were used to estimate the localization and cellular distribution of key regulatory factors NFκB and p53. Results: Compound DK-164 has well pronounced cytotoxicity greater to cancer cells (MDA-MB-231 and MCF-7) compared to non-cancerous (MCF-10A). IC50 of the substance caused a cell cycle arrest in G1 phase and induced apoptosis up to 24 hours in both tumor cells, although being more pronounced in MCF-7, a functional p53 cell line. Treatment with IC50 concentration of the compound provoked autophagy in both tumor lines but is better pronounced in the more aggressive cancer line (MDA-MB-231). Conclusion: The tested compound DK-164 showed promising properties as a potential therapeutic agent.

In Vitro Anticancer Activity of Two Ferrocene-Containing Camphor Sulfonamides as Promising Agents against Lung Cancer Cells

“…One disadvantage of metal–organic compounds is their pronounced hydrophobicity and poor solubility in a physiological environment. The previously characterised ferrocene sulfonamide, DK-164 [ 12 ] (See Supplementary Figure S1 ), showed promising antitumour activity and selectivity on breast cancer cell lines but problematic water solubility. To improve the solubility of DK-164, a series of synthetic modifications were performed to structurally optimise the compound in which increased hydrophilicity was achieved by substituting functional groups ( Figure 1 ).…”

“…The control group of cells received a medium containing only 0.5% DMSO. The cells were incubated for 72 h. MTT was performed according to the manufacturer’s protocol and as already described [ 12 ]. Absorbance was measured on an ELISA plate reader Varioscan Lux (Thermo Fisher Scientific, Waltham, MA, USA) with a test wavelength of 570 nm.…”

“…The coverslips were mounted in ProLong Diamond mounting media (Thermo Fisher Scientific, Waltham, MA, USA) containing 400 ng/mL DAPI. Images and consequent image analysis were performed as previously described [ 12 ].…”

“…In our previous investigations, a newly synthesised ferrocene-containing camphor sulfonamide DK-164 was tested on two breast cancer and one breast non-cancer cell lines and showed promising anticancer activity [ 12 ] (see Supplementary Figure S1 ). However, its main disadvantage was the poor solubility in aqueous media.…”

The antitumor activity of cannabidiol on lung cancer cell lines A549 and H1299: the role of apoptosis

“…For apoptosis detection a FITC Annexin V/Dead Cell Apoptosis Kit (Thermo Fisher Scientific) was used [24]. Approximately 3 × 10 5 cells/mL treated with cannabidiol concentrations corresponding to IC25, IC50 and IC75 values were stained in green with FITC Annexin V followed by staining the DNA in red with propidium iodide according to the manufacturer's protocol.…”