A trans-platinum(II) complex induces apoptosis in cancer stem cells of breast cancer

A reactive oxygen species-generating, cyclooxygenase-2 inhibiting, cancer stem cell-potent tetranuclear copper(ii) cluster

“…Most of the CSC specific small molecules undergoing clinical trials are organic in nature, 7 however, we and others have shown that metal complexes also display attractive anti-CSC and -bulk cancer cell properties. [8][9][10][11][12][13][14][15] Our previous work has shown that reactive oxygen species (ROS) elevation in combination with cyclooxygenase-2 (COX-2) inhibition by mononuclear copper(II)-nonsteroidal antiinflammatory drug (NSAID) complexes enables CSC and bulk cancer cell toxicity. 9,10,13 The success of this strategy is attributed to the vulnerability of CSCs and bulk cancer cells to changes in their intracellular redox state 16,17 and the overexpression of COX-2 18,19 in certain CSCs and bulk cancer cells.…”

Synthesis, DNA‐/bovine serum albumin‐binding affinity, and cytotoxicity of dinuclear platinum(II) complexes with 1,6‐naphthyridine‐bridging ligand

“…Various Pt(II) complexes trigger apoptotic cell death. [61][62][63] Accordingly, Annexin V/PI staining was performed to determine potential pro-apoptotic activity of complex Pt1 on the 4T1 and A549 cells. After 24-h treatment with Pt1 complex (46.405 μM), the population of apoptotic 4T1 cells in early apoptotic stage was fourfold higher compared with untreated 4T1 cells (12.70% vs. 3.01%) ( Figure 5).…”

The Next Generation of Anticancer Metallopharmaceuticals: Cancer Stem Cell‐Active Inorganics

“…Although efforts are underway to develop platinum agents that can remove bulk cancer cells and CSCs at clinically relevant concentrations, only one such example has been reported. A square‐planar, platinum(II) complex, trans ‐[PtCl 2 {2‐(2‐hydroxyethyl)pyridine} 2 ] ( 1 ) (Scheme ), has been identified to significantly reduce the viability of breast cancer cells overexpressing stemness markers, Oct‐4 and Sox2, in a dose‐dependent manner . Importantly, platinum(II) complex 1 removes 90 % of breast CSCs upon dosage at micromolar concentrations [IC 90 =(47.2±3.9) μ m] , whereas cisplatin and carboplatin do not (IC 90 >100 μ m ).…”

“…As quare-planar,p latinum(II) complex, trans-[PtCl 2 {2-(2-hydroxyethyl)pyridine} 2 ]( 1) (Scheme 1), has been identified to significantly reducet he viability of breast cancerc ells overexpressing stemness markers, Oct-4 and Sox2, in ad ose-dependentm anner. [15] Importantly, platinum(II) complex 1 removes 90 %o fb reast CSCsu pon dosagea tm icromolar concentrations [IC 90 = (47.2 AE 3.9) mm], whereas cisplatin and carboplatin do not (IC 90 > 100 mm). Owing to their stem-cell-like properties, CSCs can form multicellular three-dimensional structures called spheroids (mammospheres for breast CSCs).…”