Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell line

Abstract

For the development of anticancer drugs with higher activity and reduced toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II) counterparts and loading...

Triphenyltin(IV) Carboxylates with Exceptionally High Cytotoxicity against Different Breast Cancer Cell Lines

“…The investigated complexes showed much higher activity with respect to the structurally similar complex with an ibuprofenate ligand ([Ph 3 Sn(IBF)]) which has been found to be active against the Caco-2 colorectal adenocarcinoma cell line, but only remotely active or completely inactive against the DU145 (prostate carcinoma) cells and the HCT-15 (colon adenocarcinoma) cells, respectively [ 55 ]. In our previous study, flurbiprofen was used as an axial ligand of a cisplatin-based platinum(IV) conjugate and the cytotoxic activity of this cis , trans , cis -[PtCl 2 (FBP) 2 (NH 3 ) 2 ] complex was assessed against the same four breast carcinoma cell lines used in the present study [ 61 ]. The obtained results show very similar cytotoxic activity for [Ph 3 Sn(FBP)] and the cisplatin-flurbiprofenate complex suggesting that both NSAID-metal complexes with tin(IV) and platinum(IV) are highly active.…”

“…The cisplatin-indomethacinate (IND) conjugate was even able to overcome resistance expressed towards cisplatin by MDA-MB-231 breast carcinoma cells [ 60 ]. The racemic cisplatin-flurbiprofenate (FBP) conjugate showed even higher cytotoxic potency against four different breast cancer cell lines (MCF-7, HCC-1937, MDA-MB-468, BT-474) [ 61 ]. In order to assess how the metal ion affects the biological activity, we have also prepared two triphenyltin(IV) complexes with indomethacin and racemic flurbiprofen (corresponding carboxylate anions), namely [Ph 3 Sn(IND)] and [Ph 3 Sn(FBP)] ( Figure 1 ).…”

Synthesis, Characterization and Biological Investigation of the Platinum(IV) Tolfenamato Prodrug–Resolving Cisplatin-Resistance in Ovarian Carcinoma Cell Lines

“…Since the development of Platin- A in 2014, a cisplatin-based platinum(IV) complex with aspirin as axial ligand, and the investigation of conjugates of cisplatin-based platinum(IV) complexes with ibuprofen and indomethacin, interest in the conjugation of non-steroidal anti-inflammatory drugs (NSAIDs) to the platinum(IV) center as promising prodrugs with higher efficacy and reduced side-effects increased [ 26 , 29 , 30 , 31 ]. Dual-action platinum(IV) complexes with one or two axial NSAID ligands and triple-action platinum(IV) complexes with another axial bioactive moiety were synthesized and tested due to their therapeutic potency [ 26 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. NSAIDs show anti-inflammatory, antipyretic, and analgesic properties because of the inhibition of cyclooxygenases (COX) [ 26 , 44 , 45 , 46 ], which form eicosanoids including prostaglandins from arachidonic acid to preserve normal physiological features and are involved in the immune response [ 26 , 44 , 47 , 48 , 49 ].…”

“…NSAIDs show anti-inflammatory, antipyretic, and analgesic properties because of the inhibition of cyclooxygenases (COX) [ 26 , 44 , 45 , 46 ], which form eicosanoids including prostaglandins from arachidonic acid to preserve normal physiological features and are involved in the immune response [ 26 , 44 , 47 , 48 , 49 ]. One isoform of COX, COX-2, is highly expressed under inflammatory conditions and is concerned in pathological processes that cause carcinogenesis, including inhibition of apoptosis, angiogenesis, and metastasis [ 43 , 44 , 49 , 50 , 51 , 52 , 53 ]. Clinical studies to examine the potential of NSAIDs in cancer prevention showed their anti-tumor activity and preventive effects; for example, the administration of aspirin demonstrated prophylaxis in the treatment of bladder, colorectal, breast, and lung cancers [ 44 , 50 , 54 , 55 , 56 , 57 ].…”

Mesoporous Silica Nanoparticles Enhance the Anticancer Efficacy of Platinum(IV)-Phenolate Conjugates in Breast Cancer Cell Lines

“…The use of SBA-15 as a cisplatin carrier in earlier studies has been associated with increased cytotoxicity in leukemic cells [ 45 ], a twenty-fold greater antiproliferative effect in HT-29 colon cancer cells [ 46 ] and activation of pathways that change the phenotype of cancer cells (i.e., melanoma B16 tumor cells differentiate into senescent cells) [ 47 ]. Formerly reported SBA-15 nanoparticles loaded with platinum(IV) conjugates have also demonstrated very high antiproliferative activity against different breast cancer cell lines, while maintaining the structural integrity and allowing for relatively slow release of the active compounds [ 48 ].…”