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Investigating the Apoptosis Ability of Ethylenediamine 8-Hydroxyquinolinato Palladium (II) Complex.

ABSTRACT: Purpose: High solubility, low renal toxicity and apoptosis-inducing ability of palladium complexes are the reasons for their synthesis. Methods: In vitro cytotoxic study of previously synthesized [Pd(en)(8HQ)]NO3 , was carried out on breast cancer MCF-7 cell lines and prostate cancer DU145 cell lines. DNA fragmentation indicative of apoptotic was also evaluated by TUNEL assay on DU145 cell line. Results: FT-IR spectra of final complex confirmed the existence of chelating ligands. The DU145 cells unlike the MCF-7 cells, demonstrated the significant influence of the Pd (II) complex. The IC50 values of [Pd(en)(8HQ)]NO3 and cisplatin on DU145 cells were 27 and 8.3 μM, respectively. Moreover, nearly 38% apoptosis was evident in DU145 cells after treatment with [Pd(en)(8HQ)]NO3. Conclusion: [Pd(en)(8HQ)]NO3 has great potential in DNA binding and induction of apoptosis; thus it can be used in the future against prostate cancer.

SUBMITTER: Mansouri-Torshizi H

PROVIDER: S-EPMC5071809 | biostudies-other | 2016 Sep

REPOSITORIES: biostudies-other

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Investigating the Apoptosis Ability of Ethylenediamine 8-Hydroxyquinolinato Palladium (II) Complex.

Mansouri-Torshizi Hassan H Rezaei Elham E Kamranfar Farzaneh F Heidari Majd Mostafa M

Advanced pharmaceutical bulletin 20160925 3

Purpose: High solubility, low renal toxicity and apoptosis-inducing ability of palladium complexes are the reasons for their synthesis. Methods: In vitro cytotoxic study of previously synthesized [Pd(en)(8HQ)]NO3 , was carried out on breast cancer MCF-7 cell lines and prostate cancer DU145 cell lines. DNA fragmentation indicative of apoptotic was also evaluated by TUNEL assay on DU145 cell line. Results: FT-IR spectra of final complex confirme ...[more]

PMID: 27766230

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Project description:Photodynamic therapy (PDT) represents a minimally invasive and highly localized treatment strategy to ablate tumors with few side effects. In PDT, photosensitizers embedded within tumors are activated by light and undergo intersystem crossing, followed by energy transfer to molecular oxygen, resulting in the production of toxic singlet oxygen (1O2). Previously, we reported a robust, linear tetrapyrrole palladium(II) complex, Pd[DMBil1], characterized by its facile and modular synthesis, broad absorption profile, and efficient 1O2 quantum yield of ΦΔ = 0.8 in organic media. However, the insolubility of this porphyrinoid derivative in aqueous solution prevents its use under biologically relevant conditions. In this work, we report the synthesis of Pd[DMBil1]-PEG750, a water-soluble dimethylbiladiene derivative that is appended with a poly(ethylene) glycol (PEG) functionality. Characterization of this complex shows that this PEGylated biladiene architecture maintains the attractive photophysical properties of the parent complex under biologically relevant conditions. More specifically, the absorption profile of Pd[DMBil1]-PEG750 closely matches that of Pd[DMBil1] and obeys the Beer-Lambert Law, suggesting that the complex does not aggregate under biologically relevant conditions. Additionally, the emission spectrum of Pd[DMBil1]-PEG750 retains the fluorescence and phosphorescence features characteristic of Pd[DMBil1]. Importantly, the PEGylated photosensitizer generates 1O2 with ΦΔ = 0.57, which is well within the range to warrant interrogation as a potential PDT agent for treatment of cancer cells. The Pd[DMBil1]-PEG750 is biologically compatible, as it is taken up by MDA-MB-231 triple negative breast cancer (TNBC) cells and has an effective dose (ED50) of only 0.354 μM when exposed to λex > 500 nm light for 30 min. Impressively, the lethal dose (LD50) of Pd[DMBil1]-PEG750 without light exposure was measured to be 1.87 mM, leading to a remarkably high phototoxicity index of ∼5300, which is vastly superior to existing photosensitizers that form the basis for clinical PDT treatments. Finally, through flow cytometry experiments, we show that PDT with Pd[DMBil1]-PEG750 induces primarily apoptotic cell death in MDA-MB-231 cells. Overall these results demonstrate that Pd[DMBil1]-PEG750 is an easily prepared, biologically compatible, and well-tolerated photochemotherapeutic agent that can efficiently drive the photoinduced apoptotic death of TNBC cells.

Dataset Information

Investigating the Apoptosis Ability of Ethylenediamine 8-Hydroxyquinolinato Palladium (II) Complex.

Publications

Investigating the Apoptosis Ability of Ethylenediamine 8-Hydroxyquinolinato Palladium (II) Complex.

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