Improved in vitro antitumor potential of (O,O′-Diisobutyl-ethylenediamine-N,N′-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions

Bulatović, Mirna; Kaluđerović, Milena R.; Mojić, Marija; Zmejkovski, Bojana B.; Hey‐Hawkins, Evamarie; Vidaković, Melita; Grdović, Nevena; Kaluđerović, Goran N.; Mijatović, Sanja; Maksimović‐Ivanić, Danijela

doi:10.1016/j.ejphar.2015.04.012

Cited by 8 publications

(3 citation statements)

References 52 publications

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“…By analogy, the Pt(IV) anticancer active compounds developed recently bearing a similar structure to ormaplatin are also anticipated to be reduced extracellularly. [63][64][65] Also recently, the oxidation of DNA related molecules by ormaplatin was carried out experimentally or theoretically, [66][67][68] highlighting the importance of ormaplatin and its structural type; the oxidation was found to proceed via several pathways different from those described in Scheme 2 but the redox rates were sluggish or much slower than those between ormaplatin and the reductants observed in this work. Therefore, the slow redox kinetics and mechanisms are very difficult to validate in vivo, 66-68 because the surviving time of ormaplatin is too short, according to the kinetics studied here.…”

Section: Rate Comparisonsmentioning

confidence: 72%

Reduction of ormaplatin and cis-diamminetetrachloroplatinum(iv) by ascorbic acid and dominant thiols in human plasma: kinetic and mechanistic analyses

et al. 2016

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The reductions of Pt(iv) anticancer prodrugs [Pt(dach)Cl4] (ormaplatin/tetraplatin), cis-[Pt(NH3)2Cl4], and cis,cis,trans-[Pt(NH3)2Cl2Br2] by the several dominant reductants in human plasma have been characterized kinetically in this work, including l-ascorbic acid (Asc), l-glutathione (GSH), l-cysteine (Cys), dl-homocysteine (Hcy), and a dipeptide Gly-Cys. All the reductions follow an overall second-order kinetics, being first-order each in [Pt(iv)] and in the [reductant]. A general reactivity trend of Asc < Hcy < Cys-Gly < GSH < Cys is clearly revealed for the reductions of [Pt(dach)Cl4] and [Pt(NH3)2Cl4] at 37.0 °C and pH 7.40. Analysis of the observed second-order rate constants k' implies that these Pt(iv) prodrugs have a very short lifetime (less than a minute) in human plasma and can hardly enter into cells before reduction and that Asc might not play a dominant role in the reduction process among the reductants. The reductions of [Pt(dach)Cl4] and [Pt(NH3)2Cl4] by Asc have been studied in a wide pH range, and a reaction mechanism has been proposed involving parallel reductions of the Pt(iv) complexes by the Asc protolytic species. Moreover, a halide-bridged (inner-sphere) electron transfer mode for the rate-determining steps is discussed in detail; several lines of evidence strongly bolster this type of electron transfer. Furthermore, the observed activation parameters corresponding to k' have been measured around pH 7.40. Analysis of the established k'-pH profiles indicates that k' is a composite of at least three parameters in the pH range of 5.74-7.40 and the measured activation parameters in this range do not correspond to a single rate-determining step. Consequently, the isokinetic relationship reported previously using the measured ΔH(‡) and ΔS(‡) in the above pH range might be an artifact since the relationship is not justified anymore when our new data are added.

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Section: Rate Comparisonsmentioning

confidence: 72%

Reduction of ormaplatin and cis-diamminetetrachloroplatinum(iv) by ascorbic acid and dominant thiols in human plasma: kinetic and mechanistic analyses

et al. 2016

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“…It looks that cancer stem cells are more adapted to hypoxic conditions than differentiated tumor cells, due to their quiescence and low-energetic demands [21]. However, because tumor cells are not engaged in tissue homeostasis, tumor-associated hypoxia is a pathophysiologic state [22–24], caused by corrupted microcirculation which became a central issue and impediment in tumor biology and treatment, since hypoxic regions show resistance to the radio- and chemotherapy thus being negative prognostic and predictive indicators [25, 26]. Moreover, it has been demonstrated that the hypoxia and HIF-1 stabilization may lead to reduced activity of macrophages, which become unable to phagocyte tumor cells.…”

Section: Persistence Of Chronic Inflammation and Hypoxia In Tmementioning

confidence: 99%

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

Trivanović

Krstić

Djordjević

et al. 2016

Mediators of Inflammation

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State of tumor microenvironment (TME) is closely linked to regulation of tumor growth and progression affecting the final outcome, refractoriness, and relapse of disease. Interactions of tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. Due to their outstanding features, stem cell-like properties, capacity to regulate immune response, and dynamic functional phenotype dependent on microenvironmental stimuli, MSCs have been perceived as important players in TME. Signals provided by tumor-associated chronic inflammation educate MSCs to alter their phenotype and immunomodulatory potential in favor of tumor-biased state of MSCs. Adjustment of phenotype to TME and acquisition of tumor-promoting ability by MSCs help tumor cells in maintenance of permissive TME and suppression of antitumor immune response. Potential utilization of MSCs in treatment of tumor is based on their inherent ability to home tumor tissue that makes them suitable delivery vehicles for immune-stimulating factors and vectors for targeted antitumor therapy. Here, we review data regarding intrusive effects of inflammatory TME on MSCs capacity to affect tumor development through modification of their phenotype and interactions with immune system.

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“…The viability of the cells was measured by CV and MTT assays as described previously. 50 Absorbance was measured using a 96well plate reader (Tecan Spectra, Crailsheim, Germany). IC 50 [mM] and MC 50 [mg mL À1 ] values, dened as the concentration of the compounds at which 50% of cell inhibition occur were calculated using four-parameter logistic function and presented as mean from three independent experiments.…”

Section: And Mtt Assaysmentioning

confidence: 99%

SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells

et al. 2016

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Improved in vitro antitumor potential of (O,O′-Diisobutyl-ethylenediamine-N,N′-di-3-propionate)tetrachloridoplatinum(IV) complex under normoxic and hypoxic conditions

Cited by 8 publications

References 52 publications

Reduction of ormaplatin and cis-diamminetetrachloroplatinum(iv) by ascorbic acid and dominant thiols in human plasma: kinetic and mechanistic analyses

Reduction of ormaplatin and cis-diamminetetrachloroplatinum(iv) by ascorbic acid and dominant thiols in human plasma: kinetic and mechanistic analyses

The Roles of Mesenchymal Stromal/Stem Cells in Tumor Microenvironment Associated with Inflammation

SBA-15 mesoporous silica particles loaded with cisplatin induce senescence in B16F10 cells

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