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The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-β1, VEGF-A, and IGF-1 in an in vitro experimental model of triple-negative breast cancers

  • Philippe ColleryEmail author
  • Vijay Veena
  • Adhikesavan Harikrishnan
  • Didier Desmaele
PRECLINICAL STUDIES
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Summary

The rhenium(I)-diselenoether complex (Re-diSe) is a rhenium tricarbonyl-based drug chelated by a diselenoether ligand. In this work, we compared its inhibitory effects on the hormone-independent MDA-MB231cancer line and other different cancer cell lines after an exposure time of 72 h by MTT assays. The sensitivity of MDA-MB231 was in the same range than the hormone-dependent MCF-7 breast cancer, the PC-3 prostate and HT-29 colon cancer cells, while the A549 lung and the HeLa uterine cancer cells were less sensitive. We compared the inhibitory effects of Re-diSe and of its diselenide ligand (di-Se) on MDA-MB231 and a normal HEK-293 human embryonic cell line, after 72 h and 120 h of exposure. The cytotoxicity was also studied by flow cytometry using ethidium bromide assays, as well as the effects on the ROS production by DFCA-test, while the levels of TGF-β1, VEGF-A, IGF-1 were addressed by ELISA tests. The dose required to inhibit 50% of the proliferation (IC50) of MDA-MB231 breast cancer cells decreased with the time of exposure to 120 h, while the free ligand (di-Se) was found poorly active, demonstrating the important role of Re in this Re-diSe combination. The cytotoxic effects of Re-diSe were highly selective for cancer cells, with a significant increase of the number of dead cancer cells at 5 μM for an exposure time of 120 h, while normal cells were not affected. A remarkable and significant decrease of the production of ROS together with a decrease of VEGF-A, TGF-β1, and IGF-1 by the cancer cells were also observed when cancer cells were exposed to Re-diSe.

Key-words

Rhenium(I)-diselenoether Rhenium Selenium Cancer Selectivity ROS VEGF IGF TGF 

Notes

Compliance with ethical standards

Conflict of interest

Philippe Collery declares that he is owner of a patent on “Rhenium complexes and their pharmaceutical use ». Vijay Veena, Adhikesavan Harikrishnan and Didier Desmaelec declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Authors and Affiliations

  1. 1.Society for the Coordination of Therapeutic ResearchesAlgajolaFrance
  2. 2.Société de Coordination de Recherches ThérapeutiquesAlgajolaFrance
  3. 3.Biotechnology DepartmentREVA UniversityBangaloreIndia
  4. 4.Institut GalienUniversité Paris-SaclayChâtenay-MalabryFrance

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