Differential toxic effect ofcis-platinum(II) and palladium(II) chlorides complexed with methyl 3,4-diamine-2,3,4,6-tetradeoxy-?-L-lyxo-hexopyranoside in mouse lymphoma cell lines differing in DSB and NER repair ability

Kruszewski, Marcin; Boużyk, Elżbieta; Ołdak, Tomasz; Samochocka, K.; Fuks, L.; Lewandowski, W.; Fokt, Izabela; Priebe, Waldemar

doi:10.1002/tcm.10046

Cited by 17 publications

(9 citation statements)

References 31 publications

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“…Although the use of wortmannin when using proliferation assays is not the best tool to asses DNA repair unambiguously, the experiments are interesting as they constitute evidence of a different behavior of Pd 2 ‐Spm relative to cDDP. Therefore, whichever the route involved in the different behavior of cDDP and Pd 2 ‐Spm in the presence of wortmannin, the data presently gathered suggest that there might be a significant mechanistic difference between these compounds as verified for other Pt(II) versus Pd(II) systems (54).…”

Section: Resultsmentioning

confidence: 85%

Biologic Activity of a Dinuclear Pd(II)–Spermine Complex Toward Human Breast Cancer

Fiuza¹,

Holy²,

Carvalho³

et al. 2011

Chem Biol Drug Des

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A dinuclear palladium-based complex (Pd 2-Spm) was synthesized and compared with cisplatin (cDDP) on two different human breast cancer cell lines (MCF-7 and MDA-MB-231) as well as toward an untransformed cell line (BJ fibroblasts). The results obtained show that Pd 2-Spm is more effective against the estrogen receptors [ER())] cell line MDA-MB-231, while cDDP displayed better results for the ER(+) MCF-7 cell line. It was shown that, like cDDP, Pd 2-Spm triggers phosphorylation of H2AX, indicating that this compound damages DNA. Apart from DNA, Pd 2-Spm also targets the cytoskeleton having a greater impact on cell morphology than cDDP. Pd 2-Spm and cDDP have opposite antiproliferative activities in the presence of the PI3K inhibitor wortmannin. Furthermore , Pd 2-Spm at an optimized concentration displays a rapid antiproliferative effect as opposed to cDDP, which seems to have a slower kinetics. The results point to a distinct mechanism of action for each of these complexes, which may explain their synergistic action when coadminis-trated. Breast cancer is the most common cancer among women and one of the main causes of death in women in Portugal (1-3). Evolution of human breast cancer is related with cells¢ dependence on ovar-ian estrogens, with the presence (+) or absence ()) of estrogen receptors (ER) being an important marker for the prognosis and choice of therapeutic strategies. Generally, patients suffering from ER(+) breast cancer have better life prospects than those with breast cancer lacking ER expression, which tend to be more aggressive (66-month survival rate) (4). For advanced stages of breast cancer , chemotherapy becomes an important therapeutic option. While cisplatin [cis-diamminedichloroplatinum(II), cis-Pt(NH 3) 2 Cl 2 , cDDP, Figure 1A] is still among the most widely used drugs in cancer chemo-therapy, patients that are treated with cDDP suffer from severe side-effects and, very often, develop resistance mechanisms. These facts urge for the pursuit of improved antitumor agents, displaying lower toxicity coupled to a broader spectrum of activity. Hundreds of new cisplatin-based compounds have been synthesized to date, to overcome cisplatin's harmful side-effects while retaining efficacy. Other inorganic agents, comprising different transition metals, have also been studied (5). Pd(II) complexes are particularly interesting because although structurally similar to Pt(II), their reactivity is fairly distinct. In fact, reactions involving Pd(II) are reported to be about 10 4-10 5 faster than those with Pt(II) (6,7). This increased lability is thought to be the main reason for the biologic inactivity of some Pd(II) agents, namely, cis-diamminedichloropalladium(II) (cis-Pd(NH 3) 2 Cl 2 , cDDPd). However, despite the initial belief that Pd(II) compounds were inactive as antineoplastic agents, many have been synthesized and shown to be not only more active than cisplatin (8-10) but also more effective than their Pt(II) counterparts (11-13). Because it is broadly accepted that one of the main targets...

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Section: Resultsmentioning

confidence: 85%

Biologic Activity of a Dinuclear Pd(II)–Spermine Complex Toward Human Breast Cancer

Fiuza¹,

Holy²,

Carvalho³

et al. 2011

Chem Biol Drug Des

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“…The cytotoxicity of L-OHP in CDDP-resistant cell lines has been considered to be due to the differences of DNA damage and/or recognition processes between CDDP and L-OHP [46]. The DNA damage caused by Pd (II) compounds is reportedly processed in a different manner from that induced by Pt (II) complexes [47]. In the CDDP-resistant subline (MKN45 (CDDP)), [PdCl 2 (L)] showed significantly higher antitumor effects in vitro (Table 2) and in vivo (Figure 3) as compared with CDDP and [PtCl 2 (L)].…”

Section: Discussionmentioning

confidence: 99%

Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

et al. 2013

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BackgroundCisplatin (CDDP) is the most frequently used chemotherapeutic agent for various types of advanced cancer, including gastric cancer. However, almost all cancer cells acquire resistance against CDDP, and this phenomenon adversely affects prognosis. Thus, new chemotherapeutic agents that can overcome the CDDP-resistant cancer cells will improve the survival of advanced cancer patients.MethodsWe synthesized new glycoconjugated platinum (II) and palladium (II) complexes, [PtCl2 (L)] and [PdCl2 (L)]. CDDP-resistant gastric cancer cell lines were established by continuous exposure to CDDP, and gene expression in the CDDP-resistant gastric cancer cells was analyzed. The cytotoxicity and apoptosis induced by [PtCl2 (L)] and [PdCl2 (L)] in CDDP-sensitive and CDDP-resistant gastric cancer cells were evaluated. DNA double-strand breaks by drugs were assessed by evaluating phosphorylated histone H2AX. Xenograft tumor mouse models were established and antitumor effects were also examined in vivo.ResultsCDDP-resistant gastric cancer cells exhibit ABCB1 and CDKN2A gene up-regulation, as compared with CDDP-sensitive gastric cancer cells. In the analyses of CDDP-resistant gastric cancer cells, [PdCl2 (L)] overcame cross-resistance to CDDP in vitro and in vivo. [PdCl2 (L)] induced DNA double-strand breaks.ConclusionThese results indicate that [PdCl2 (L)] is a potent chemotherapeutic agent for CDDP-resistant gastric cancer and may have clinical applications.

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“…Intriguingly, notwithstanding the lower water solubility, the corresponding neutral analogue Pt-7 was found equally active not only in murine L1210 leukemia cells but also toward two different murine L5178Y-S and L5178Y-R lymphoma cell lines differing in their doublestrand breaks and nucleotide excision repair ability [67,68].…”

Section: Amino-sugar Derivativesmentioning

confidence: 99%

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

Pettenuzzo¹,

Pigot²,

Ronconi³

2016

Metallodrugs

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Glucose is a key source of energy and an essential nutrient for cell growth. Rapidly dividing cancer cells are well-known to require more nutrients and energy than normal ones to sustain their higher proliferation rates, and glucose is no exception. Therefore, the biomolecules involved in the promotion/regulation of the glycolytic flux may be regarded as potential targets for tackling tumor progression. Among all, glucose transporters (GLUTs), devoted to the recognition and cellular internalization of glucose, are largely overexpressed in tumors, thus indicating glycolysis as the major anaerobic glucose metabolism. Accordingly, such increased demand of glucose by fast-proliferating cancer cells makes it very attractive to selectively target tumor sites. In particular, tailored glucose-like substrates can be conjugated to chemotherapeutics (including metal-containing anticancer agents) so as to attain the site-specific delivery of drugs into the affected tissues. Progress in the development of metal-based glycoconjugates are here summarized and discussed.

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Differential toxic effect ofcis-platinum(II) and palladium(II) chlorides complexed with methyl 3,4-diamine-2,3,4,6-tetradeoxy-?-L-lyxo-hexopyranoside in mouse lymphoma cell lines differing in DSB and NER repair ability

Cited by 17 publications

References 31 publications

Biologic Activity of a Dinuclear Pd(II)–Spermine Complex Toward Human Breast Cancer

Biologic Activity of a Dinuclear Pd(II)–Spermine Complex Toward Human Breast Cancer

Anti-cancer effects of newly developed chemotherapeutic agent, glycoconjugated palladium (II) complex, against cisplatin-resistant gastric cancer cells

Metal-based glycoconjugates and their potential in targeted anticancer chemotherapy

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