Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 23;6(3):FSOA442.
doi: 10.2144/fsoa-2019-0057.

Antitumor activity of new chemical compounds in triple negative mammary adenocarcinoma models

María V Giolito  1 , Cristian M Camacho  2 , Maitena Martinez-Amezaga  2 , Carla I Traficante  2 , Rocío A Giordano  1 , Patricia G Cornier  2 , Ernesto G Mata  2   3 , Carina Ml Delpiccolo  2   3 , Dora B Boggián  2   4 , Antonela Del Giúdice  1 , Leandro E Mainetti  1   3 , Olga G Scharovsky  1   3   4 , Viviana R Rozados  1   3 , María J Rico  1   3
Affiliations

Antitumor activity of new chemical compounds in triple negative mammary adenocarcinoma models

María V Giolito et al. Future Sci OA. .

Abstract

Aim: According to the need for the development of new anticancer agents, we have synthetized novel bioactive compounds and aimed to determine their antitumor action.

Materials & methods: We describe in vitro studies evaluating the effect of 35 novel chemical compounds on two triple negative murine mammary adenocarcinoma tumors.

Results & conclusion: Three compounds were selected because of their high antitumor activity and their low toxicity to normal cells. Their effect on tumor cells apoptosis, clonogenicity and migratory capacity, were determined. We found that the selected compounds showed inhibition of viability and clonogenic capacity, and promotion of apoptosis. They also decreased the migratory capacity of tumor cells. The results obtained suggest the likelihood of their future use as antitumor and/or antimetastatic agents.

Keywords: antitumor effect; chemical agents; in vitro assays; triple negative mammary adenocarcinoma.

PubMed Disclaimer

Conflict of interest statement

Financial & competing interests disclosure The work was supported by grants of Universidad Nacional de Rosario to MJR (1MED474). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Screening process.
Figure 2.
Figure 2.. Effect of the compounds in cells viability.
Effect on 4T1 (A), MDA-MB-231 (B) and MDCK (C) cells viability. 4T1, MDA-MB-231 and MDCK cells were incubated for 36 h in complete medium with 25 μM of the compounds. Viable cell number was evaluated with WST-1. Results are shown as percentage of cell viability relative to control (100%) and are expressed as mean ± SEM. Experiments were performed in triplicate. SEM: Standard error of the mean.
Figure 3.
Figure 3.. Chemical structure of the selected compounds.
Figure 4.
Figure 4.. Apoptosis induced by the treatment.
(A) After 18 h of treatment with the compounds (25 μM), 4T1 cells were collected, washed and stained with Annexin V-FITC and propidium iodide. It shows the percentage of Annexin V+ cells (median [range] of three independent experiments); (Mann–Whitney test) compared with control cells; (B) Flow cytometry profiles for each compound; (C) After 18 h of treatment with the selected compounds CIT171B3, CMC266 and PGC22i (25 μM), apoptotic cells were identified in sections of paraffin-embedded cells, using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-peroxidase nick end labeling assay. The table shows the ratio between the percentage of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-peroxidase nick end labeling positive-treated cells and the percentage obtained in nontreated control cells; (D) Photos representative of each treatment 1000X. *p < 0.05. DAPI: 4′,6-diamidino-2-phenylindole; TUNEL: Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-peroxidase nick end labeling.
Figure 5.
Figure 5.. Effect on clonogenic and migratory capacity.
Treatment with 10 μM (day 6): (A) Number of colonies (median [range]; Mann–Whitney test); (B) Diameter in mm (mean ± standard error of the mean of three independent experiments; Student's t-test). Representative images of: (C) Colonies (Giemsa staining); (D) Colony morphology taken under inverted microscope (100×); (E) Cell motility was estimated by measuring closure of the initial wound (% respect to the initial wound) incubating with the compounds (10 μM). Quantification was performed using the Image J software and data are shown as median (range) of three independent experiments; (F) Photos taken at 0 and 11 hs (100×). *p < 0.05. SEM: Standard error of the mean.
See this image and copyright information in PMC

References

    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68(6), 394–424 (2018). - PubMed
    1. Jiao Q, Wu A, Shao G. et al. The latest progress in research on triple negative breast cancer (TNBC): risk factors, possible therapeutic targets and prognostic markers. J. Thorac. Dis. 6(9), 1329 (2014). - PMC - PubMed
    1. Hopkins AL. Network pharmacology: the next paradigm in drug discovery. Nat. Chem. Biol. 4(11), 682–690 (2008). - PubMed
    1. Dolle RE. Historical overview of chemical library design. In: Chemical Library Design. Springer, Humana Press, 3–25 (2011). - PubMed
    1. Nicolaou KC. Advancing the drug discovery and development process. Angew. Chem. Int. Ed. Engl. 53(35), 9128–9140 (2014). - PubMed

LinkOut - more resources