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Old 01-12-2019, 07:35 AM
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rss IGF - The rhenium(I)-diselenoether anticancer drug targets ROS, TGF-?1, VEGF-A, and I

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

Invest New Drugs. 2019 Jan 11;:

Authors: Collery P, Veena V, Harikrishnan A, Desmaele D

Abstract
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-?1, 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.?M 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-?1, and IGF-1 by the cancer cells were also observed when cancer cells were exposed to Re-diSe.


PMID: 30632005 [PubMed - as supplied by publisher]



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