The role of cell cycle progression for the apoptosis of cancer cells induced by palladium(II)-saccharinate complexes of terpyridine

Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent

“…Pd(II) has been recognized as one of the best candidates due to its physical-chemical similarities to Pt(II) [8,14]. Indeed, several Pd(II) complexes have been tested in vitro for anti-tumor properties in breast [19][20][21][22][23], lung [24,25], colon [26][27][28], prostate [29][30][31], gastric [32], liver [33], and other human cancer cell lines [34][35][36][37]. In some cases, favorable antiproliferative and cytotoxic properties have been reported for Pd (II) agents [20,24,28], compared to Pt(II) analogs, along with antimetastatic properties (antiangiogenic and anti-migratory [22]), lower acquired resistance [36], and lesser toxicity towards non-neoplastic cells [20].…”

“…In some cases, favorable antiproliferative and cytotoxic properties have been reported for Pd (II) agents [20,24,28], compared to Pt(II) analogs, along with antimetastatic properties (antiangiogenic and anti-migratory [22]), lower acquired resistance [36], and lesser toxicity towards non-neoplastic cells [20]. Favorable ligands to soft-ions such as Pt(II) and Pd(II) comprise biogenic polyamines (PA) [26,27], e.g., putrescine (H2N(CH2)4NH2, Put), spermidine (H2N(CH2)4NH(CH2)3NH2, Spd) and spermine (H2N(CH2)3NH(CH2)4NH(CH2)3NH2, Spm), all essential polycations impacting on eukaryotic cell growth and differentiation [38]. The resulting polynuclear chelates have been shown to target cellular DNA (at concentrations as low as 5 μg/mL) [39,40] through non-conventional interactions (inter-strand, long-range) [41,42], thus inducing significant cytotoxicity against several types of human cancer cells [19][20][21]35,36,43].…”

Exploring the Potential of Metallodrugs as Chemotherapeutics for Triple Negative Breast Cancer

“…[43] We include two other types of compounds (14 and 15 in Scheme 3) not mentioned in this review, and interesting due to: a) their cytotoxicity on TNBC cells with enhanced apoptotic effects and phototoxic activity in the presence of visible light ( 14), [44] and b) forming a metallosupramolecular structure (compound 15) that resulted highly cytotoxic on TNBC cells by membrane disruption through the helicate structure. [45] Scheme 3 also depicts structures of two types of compounds (16 and 17-19) mentioned in the review, [43] that we consider more relevant as their mechanisms have been studied more in depth [46][47][48][49][50][51][52][53] including some in vivo studies on mice (but not on TBNC tumors). [49,50,52] The binuclear cyclometallated Pd(II) compound [Pd(CN)Cl(dppe)] (16, AJ-5) was found to be highly cytotoxic to the TNBC MDA-MB-231 cell line (IC 50 = 0.193 μM, 48 h) while being less cytotoxic to normal cells.…”

“…[45] Scheme 3 also depicts structures of two types of compounds (16 and 17-19) mentioned in the review, [43] that we consider more relevant as their mechanisms have been studied more in depth [46][47][48][49][50][51][52][53] including some in vivo studies on mice (but not on TBNC tumors). [49,50,52] The binuclear cyclometallated Pd(II) compound [Pd(CN)Cl(dppe)] (16, AJ-5) was found to be highly cytotoxic to the TNBC MDA-MB-231 cell line (IC 50 = 0.193 μM, 48 h) while being less cytotoxic to normal cells. [46] It was found that compound 14 has in vitro activity against MCF7 derived stem-like cells, that induces DNA damage (inducing double strand breaks DSBs) leading to G1 cycle cell arrest (increased levels of p21 were found but not of p-53 suggesting a p53independent mechanism).…”

“…[46] In a different study it was demonstrated that compound 16 inhibits melanoma growth in nude mice without any noticeable side-effects. [47] Ulukaya and co-workers reported on a series of cationic palladium (II) compounds containing saccharinate and triamine ligands such bis(pyridinylmethyl)amine (bmpa) [48] or 2,2':6',2''terpyridine (terpy) [49][50][51][52][53] which were found effective on TNBC cell lines, [48][49][50][51][52][53] and in some cases, in mice models [49,50,53] (selected compounds 17-19 in Scheme 3). The compounds are apoptotic.…”