The
triple-negative breast cancer subtype (TNBC) is highly aggressive
and metastatic and corresponds to 15–20% of diagnosed cases.
TNBC treatment is hampered, because these cells usually do not respond
to hormonal therapy, and they develop resistance to chemotherapeutic
drugs. On the other hand, the severe side effects of cisplatin represent
an obstacle for its clinical use. Ruthenium (Ru)-based complexes have
emerged as promising antitumor and antimetastatic substitutes for
cisplatin. In this study, we demonstrated the effects of a Ru/biphosphine
complex, containing gallic acid (GA) as a ligand, [Ru(GA)(dppe)2]PF6, hereafter called Ru(GA), on a TNBC cell line,
and compared them to the effects in a nontumor breast cell line. Ru(GA)
complex presented selective cytotoxicity against TNBC over nontumor
cells, inhibited its migration and invasion, and induced apoptosis.
These effects were associated with the increased amount of transferrin
receptors (TfR) on tumor cells, compared to nontumor ones. Silencing
of TfR decreased Ru(GA) effects on TNBC cells, demonstrating that
these receptors were at least partially responsible for Ru(GA) delivery
into tumor cells. The Ru(GA) compound must be further studied in different
in vivo assays in order to investigate its antitumor properties and
its toxicity in complex biological systems.
This work describes the synthesis of three news ruthenium(II) complexes with gallic acid and derivatives of general formula [Ru(L)(dppb)(bipy)]PF6, where L = gallate (GAC), benzoate (BAC), and esterified-gallate (EGA), bipy...
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