Exploring ovarian cancer cell resistance to rhenium anticancer complexes.

Title Exploring ovarian cancer cell resistance to rhenium anticancer complexes.
Authors S.C. Marker; A.Paden King; R.V. Swanda; B. Vaughn; E. Boros; S.B. Qian; J.J. Wilson
Journal Angew Chem Int Ed Engl
DOI 10.1002/anie.202004883

Rhenium tricarbonyl complexes have been recently investigated as novel anticancer agents. However, little is understood about their mechanisms of action, as well as the means by which cancer cells respond to chronic exposure to these compounds. To gain a deeper mechanistic insight into these rhenium anticancer agents, we developed and characterized an ovarian cancer cell line that is resistant to a previously studied compound [Re(CO) 3 (dmphen)(ptolICN)] + , where dmphen = 2,9-dimethyl-1,10-phenanthroline and p tolICN = para -tolyl isonitrile, called TRIP. This TRIP-resistant ovarian cancer cell line, A2780TR, was found to be 9 times less sensitive to TRIP compared to the wild-type A2780 ovarian cancer cell line. Furthermore, the cytotoxicities of established drugs and other rhenium anticancer agents in the TRIP-resistant cell line were determined. Notably, the drug taxol was found to exhibit a 184-fold decrease in activity in the A2780TR cell line, suggesting that mechanisms of resistance towards TRIP and this drug are similar. Accordingly, expression levels of the ATP-binding cassette transporter P-glycoprotein, an efflux transporter known to detoxify taxol, were found to be elevated in the A2780TR cell line. Additionally, a gene expression analysis using the National Cancer Institute 60 cell line panel identified the MT1E gene to be overexpressed in cells that are less sensitive to TRIP. Because this gene encodes for metallothioneins, this result suggests that detoxification by this class of proteins is another mechanism for resistance to TRIP. The importance of this gene in the A2780TR cell line was assessed, confirming that its expression is elevated in this cell line as well. As the first study to investigate and identify the cancer cell resistance pathways in response to a rhenium complex, this report high-lights important similarities and differences in the resistance responses of ovarian cancer cells to TRIP and conventional drugs.

Citation S.C. Marker; A.Paden King; R.V. Swanda; B. Vaughn; E. Boros; S.B. Qian; J.J. Wilson.Exploring ovarian cancer cell resistance to rhenium anticancer complexes.. Angew Chem Int Ed Engl. 2020. doi:10.1002/anie.202004883

Related Elements


See more Rhenium products. Rhenium (atomic symbol: Re, atomic number: 75) is a Block D, Group 7, Period 6 element with an atomic weight of 186.207. The number of electrons in each of rhenium's shells is 2, 8, 18, 32, 13, 2 and its electron configuration is [Xe] 4f14 5d5 6s2. Rhenium Bohr ModelThe rhenium atom has a radius of 137 pm and a Van der Waals radius of 217 pm. Rhenium was discovered and first isolated by Masataka Ogawa in 1908. In its elemental form, rhenium has a silvery-white appearance. Rhenium is the fourth densest element exceeded only by platinum, iridium, and osmium. Rhenium's high melting point is exceeded only by those of tungsten and carbon.Elemental Rhenium Rhenium is found in small amounts in gadolinite and molybdenite. It is usually extracted from the flue dusts of molybdenum smelters. The name Rhenium originates from the Latin word 'Rhenus' meaning "Rhine" after the place of discovery.

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