Cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms

Chen, Jing Jing; Luo, Zuandi; Zhao, Zhennan; Xie, Lina; Zheng, Wenjie; Chen, Tianfeng

doi:10.1016/j.biomaterials.2015.08.031

Cited by 51 publications

(38 citation statements)

References 62 publications

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“…In our previous studies, we found that the introduction of an electron‐donating group (−CH 3 ) was able to increase the complex lipophilicity and cellular uptake whereas the introduction of an electron‐withdrawing group (−NO 2 ) reduced these properties . The introduction of an electron‐donating group (−CH 3 , −OCH 3 , −OH) and an electron‐withdrawing group (−NO 2 , −Cl) likewise appear to have important roles in the anticancer activity of selenadiazole derivatives.…”

Section: Introductionmentioning

confidence: 99%

Selenadiazole Derivatives Inhibit Angiogenesis‐Mediated Human Breast Tumor Growth by Suppressing the VEGFR2‐Mediated ERK and AKT Signaling Pathways

Lai

Sang

et al. 2018

Chemistry An Asian Journal

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Selenadiazole derivatives (SeDs) have been found to show promise in chemo-/radiotherapy applications by activating various downstream signaling pathways. However, the functional role of SeDs on angiogenesis, which is pivotal for tumor progression and metastasis, has not yet been elucidated. In the present study, we have examined the antiangiogenic activities of SeDs and elucidated their underlying mechanisms. The results showed that the as-synthesized SeDs not only enhanced their anticancer activities against several human cancer cells but also showed more potent inhibition on human umbilical vein endothelial cells (HUVECs). The in vitro results suggested that SeDs, especially 1 a, dose-dependently inhibited the vascular endothelial growth factor (VEGF)-induced cell migration, invasion, and capillary-like structure formation of HUVECs. Compound 1 a also significantly suppressed VEGF-induced angiogenesis in a Matrigel plug assay as part of a C57/BL6 mice assay by means of down regulation of VEGF. Furthermore, we found that 1 a significantly inhibited MCF-7 human breast tumor growth in nude mice without severe systematic cytotoxicity. Compound 1 a was more effective in inhibiting cell proliferation and induced a much more pronounced apoptosis effect in endothelial cells than MCF-7 cells, which implies that endothelial cells might be the primary target of 1 a. Further mechanistic studies on tumor growth inhibition effects and neovessel formation suppression demonstrated that 1 a inhibited cell viability of MCF-7 and HUVECs by induction of cell apoptosis, accompanied by poly(adenosine diphosphate ribose)polymerase (PARP) cleavage and caspase activation. Additionally, the 1 a-induced antiangiogenesis effect was achieved by abolishing the VEGF-VEGFR2-ERK/AKT (ERK=extracellular signal-regulated kinases; AKT=protein kinease B) signal axis and enhanced the apoptosis effect by triggering reactive oxygen species (ROS)-mediated DNA damage. Taken together, these results clearly demonstrate the antiangiogenic potency of SeDs and the underlying molecular mechanisms.

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Section: Introductionmentioning

confidence: 99%

Selenadiazole Derivatives Inhibit Angiogenesis‐Mediated Human Breast Tumor Growth by Suppressing the VEGFR2‐Mediated ERK and AKT Signaling Pathways

Lai

Sang

et al. 2018

Chemistry An Asian Journal

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“…Studies have proven that the anticancer actions of drugs are associated to their intracellular localization of anticancer drugs . Previously, we found that the cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms . Cytosolic iron(II) complexes exhibited anticancer and antiangiogenic potencies by targeting mitochondria to trigger cancer cell apoptosis .…”

Section: Resultsmentioning

confidence: 99%

Cancer‐Targeting Functionalization of Selenium‐Containing Ruthenium Conjugate with Tumor Microenvironment‐Responsive Property to Enhance Theranostic Effects

Zhao

Gao

You

et al. 2018

Chemistry A European J

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A mutifunctional ruthenium‐based conjugate Ru‐BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer‐targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH‐response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule‐glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real‐time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis.

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“…In the above equations, K 12 and z are the equilibrium constant for the cross reaction and collision frequency for the uncharged reactant molecules in solution respectively. The value of z is the pre exponential factor which is often taken as 1 …”

Section: Application Of Marcus Theory Of Electron Transfermentioning

confidence: 99%

“…[9][10][11] Recently iron polypyridyl complexes have been identified as potential anticancer drug by inhibiting the cancer cell proliferation. [12] The iron(III) polypyridyl complexes are well-known one electron acceptors, [13] and several interactions of these complexes with inorganic and organic reductants have been reported. [6,[13][14][15][16][17] Many of the reactions are rationalized in terms of the outer-sphere mechanism, supported by Marcus-type dependence of rate.…”

Section: Introductionmentioning

confidence: 99%

A paradigm shift in rate determining step from single electron transfer between phenylsulfinylacetic acids and iron(III) polypyridyl complexes to nucleophilic attack of water to the produced sulfoxide radical cation: a non‐linear Hammett

Subramaniam¹,

Rose

Rathinakumari

2016

J of Physical Organic Chem

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Mechanism of oxidative decarboxylation of phenylsulfinylacetic acids (PSAAs) by iron(III) polypyridyl complexes in aqueous acetonitrile medium has been investigated spectrophotometrically. 3+ is rationalized on the basis of coordination of a water molecule at the carbon atom adjacent to the ring nitrogen of the metal polypyridyl complexes by nucleophilic attack at higher concentrations. Electron-withdrawing and electron-releasing substituents in PSAA facilitate the reaction and Hammett correlation gives an upward 'V' shaped curve. The apparent upward curvature is rationalized based on the change in the rate determining step from electron transfer to nucleophilic attack, by changing the substituents from electron-releasing to electron-withdrawing groups. Electron-releasing substituents in PSAA accelerate the electron transfer from PSAA to the complex and also stabilize the intermediate through resonance interaction leading to negative reaction constants (ρ). Conversely, electron-withdrawing groups, while retarding the electron transfer exert an accelerating effect on the nucleophilic attack of H 2 O which leading to low magnitude of ρ + compared to high ρ À values of electron-releasing groups. Marcus theory is applied, and a fair agreement is seen with the experimental values.

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Cellular localization of iron(II) polypyridyl complexes determines their anticancer action mechanisms

Cited by 51 publications

References 62 publications

Selenadiazole Derivatives Inhibit Angiogenesis‐Mediated Human Breast Tumor Growth by Suppressing the VEGFR2‐Mediated ERK and AKT Signaling Pathways

Selenadiazole Derivatives Inhibit Angiogenesis‐Mediated Human Breast Tumor Growth by Suppressing the VEGFR2‐Mediated ERK and AKT Signaling Pathways

Cancer‐Targeting Functionalization of Selenium‐Containing Ruthenium Conjugate with Tumor Microenvironment‐Responsive Property to Enhance Theranostic Effects

A paradigm shift in rate determining step from single electron transfer between phenylsulfinylacetic acids and iron(III) polypyridyl complexes to nucleophilic attack of water to the produced sulfoxide radical cation: a non‐linear Hammett

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