A ruthenium(II) β-carboline complex induced p53-mediated apoptosis in cancer cells

Chen, Yu; Qin, Mengying; Wang, Lei; Chao, Hui; Ji, Liang‐Nian; Xu, Anlong

doi:10.1016/j.biochi.2013.07.016

Cited by 40 publications

(28 citation statements)

References 51 publications

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“…20 Next we analyzed the changes in the cell cycle. Moreover, the inhibition of cancer cell proliferation could result from the induction of cell cycle arrest.…”

Section: View Article Onlinementioning

confidence: 99%

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

et al. 2015

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To evaluate the anticancer mechanism of the new ruthenium complex-Λ-WH0402 at the cellular level, the in vitro cytotoxicity of Λ-WH0402 was investigated on 10 human tumor cell lines. Λ-WH0402 was found to have higher anticancer activity than cisplatin toward human liver cancer HCCLM6 cells that have high tumor metastatic characteristics. Meanwhile, Λ-WH0402 showed an antimetastatic effect on HCCLM6 cells in vitro, mostly through its effect on cell adhesion, invasion and migration. In addition, Λ-WH0402 significantly reduced tumor metastasis to the lungs in orthotopic mouse hepatocellular cancer (HCC) models induced by HCCLM6 cells. Furthermore, Λ-WH0402 exerted an inhibitory effect on tumor cell growth and proliferation and induced dose-dependent cell cycle arrest in the S phase in HCCLM6 cells. Immunoblotting analysis showed that Λ-WH0402 not only decreased the expression of antiapoptotic protein Bcl-2 and nutrient-deprivation autophagy factor-1 (NAF-1), but also significantly increased the expression of Beclin-1 in HCCLM6 cells. More importantly, we identified that Λ-WH0402 treatment reduced the interaction between Bcl-2 and Beclin-1, and increased the expression of autophagic activation marker LC3B-II in HCCLM6 cells. On the whole, our results suggested that the anitcancer activity of Λ-WH0402 is mediated through promoting the Beclin-1-dependent autophagy pathway in HCCLM6 cells.

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“…20 Next we analyzed the changes in the cell cycle. Moreover, the inhibition of cancer cell proliferation could result from the induction of cell cycle arrest.…”

Section: View Article Onlinementioning

confidence: 99%

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

et al. 2015

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“…Recently the development of the ruthenium complexes toward their application in optical imaging of cells in hypoxia [10, 11] or as cytotoxic agents selectively activated in hypoxic cells [12] shows a new direction in design and great potency of this type of compounds. One of the most interesting research aspects is a dual imaging and therapeutic application of ruthenium polypyridyl complexes [10, 11, 13]. In this context an appropriate modification of polypyridyl ligands through the introduction of different substituents can tune cytotoxic and luminescent properties of ruthenium complexes.…”

Section: Introductionmentioning

confidence: 99%

Multifaceted interplay between lipophilicity, protein interaction and luminescence parameters of non-intercalative ruthenium(II) polypyridyl complexes controlling cellular imaging and cytotoxic properties

et al. 2014

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Here, we examine the photophysical properties of five ruthenium(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and functionalized bipyridine (R1bpy-R2, where R1 = H or CH3, R2 = H, CH3, COO−,4-[3-(2-nitro-1H-imidazol-1-yl)propyl] or 1,3-dicyclohexyl-1-carbonyl-urea) towards development of luminescence probes for cellular imaging. These complexes have been shown to interact with albumin and the formed adducts exhibited up to eightfold increase in the luminescence quantum yield as well as the average lifetime of emission. It was demonstrated that they cannot bind to DNA through the intercalation mode and its luminescence in the presence of DNA is quenching. Cell viability experiments indicated that all complexes possess significant dose-dependent cytotoxicity (with IC50 5–19 μM) on 4T1 breast cancer cell line and their anti-proliferative activity correlates very well with their lipophilicity. Cellular uptake was studied by measuring the ruthenium content in cells using ICP-MS technique. As expected, the better uptake is directly related to higher lipophilicity of doubly charged ruthenium complexes while uptake of monocationic one is much lower in spite of the highest lipophilicity. Additionally staining properties were assessed using flow cytometry and fluorescence microscopy. These experiments showed that complex with 1,3-dicyclohexyl-1-carbonyl-urea substituent exhibits the best staining properties in spite of the lowest luminescence quantum yield in buffered solution (pH 7.4). Our results point out that both the imaging and cytotoxic properties of the studied ruthenium complexes are strongly influence by the level of internalization and protein interaction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00775-014-1187-5) contains supplementary material, which is available to authorized users.

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“…Though not much information is available on induction of intrinsic pathway of apoptosis by metal complexes, a Ru(II)-arene compound [Ru(g6-p-cymene)Cl 2 (pta)] has been described to implicate this pathway for inducing apoptosis in the Ehrlich ascite carcinoma [62]. Recently, another Ru(II)-complex (Ru(II) b-carboline complex) has also been demonstrated to induce apoptosis in the cancer cells by involving p53 [63]. In this context, the findings of this paper are of special merit with regard to elucidation of the biochemical mechanism by which a Ru(II)-complex can induce p53 dependent apoptosis in the tumor cells in vivo.…”

Section: Discussionmentioning

confidence: 97%

Activation of p53 mediated glycolytic inhibition-oxidative stress-apoptosis pathway in Dalton's lymphoma by a ruthenium (II)-complex containing 4-carboxy N-ethylbenzamide

2015

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A ruthenium(II) β-carboline complex induced p53-mediated apoptosis in cancer cells

Cited by 40 publications

References 51 publications

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

Ruthenium complex Λ-WH0402 induces hepatocellular carcinoma LM6 (HCCLM6) cell death by triggering the Beclin-1-dependent autophagy pathway

Multifaceted interplay between lipophilicity, protein interaction and luminescence parameters of non-intercalative ruthenium(II) polypyridyl complexes controlling cellular imaging and cytotoxic properties

Activation of p53 mediated glycolytic inhibition-oxidative stress-apoptosis pathway in Dalton's lymphoma by a ruthenium (II)-complex containing 4-carboxy N-ethylbenzamide

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