Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug

Wang, Ying; He, Qing‐Yu; Che, Chi‐Ming; Chiu, Jen‐Fu

doi:10.1002/pmic.200402027

Cited by 82 publications

(44 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It displayed antiproliferative activity in several types of human cancer cells (Wang et al, 2005(Wang et al, , 2006Lum et al, 2006). However, the precise target and mechanism of action of gold(III) porphyrin 1a on tumour cells remain largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Preliminary data showed that gold(III) porphyrin 1a inhibited cell proliferation of wide range of human cancer cell lines, including human cervical epithelioid cancer cells, leukaemia, hepatocellular, and nasopharyngeal carcinoma cells (Che et al, 2003;Wang et al, 2005) in vitro, suggesting that this molecule may offer novel approach to cancer therapy. Very recent data showed that gold(III) porphyrin 1a induced apoptosis in human nasopharyngeal carcinoma cells through mitochondrial death pathways related to reactive oxygen species (ROS) (Wang et al, 2005(Wang et al, , 2006. However, the underlying signalling mechanism by which gold(III) porphyrin 1a modifies the intracellular apoptosis pathways in tumour cells has not been explained in detail in neuroblastoma cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Xie

Sun

et al. 2009

Br J Cancer

View full text Add to dashboard Cite

BACKGROUND: Gold(III) porphyrin 1a is a new class of anticancer drug, which inhibits cell proliferation of wide range of human cancer cell lines and induces apoptosis in human nasopharyngeal carcinoma cells. However, the underlying signalling mechanism by which gold(III) porphyrin 1a modifies the intracellular apoptosis pathways in tumour cells has not been explained in detail in neuroblastoma cells. METHODS: Cell proliferation and apoptosis were determined by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V binding, respectively. Western blot assay was used to detect proteins involved in apoptotic and Akt pathways. In vivo tumour growth was assessed by inoculating tumour cells to nude mice subcutaneously, and gold(III) porphyrin 1a was administrated intravenously. RESULTS: This study assessed the antitumour effect and mechanism of gold(III) porphyrin 1a on neuroblastoma in vitro and in vivo. Gold(III) porphyrin 1a displayed a growth inhibition and induction of apoptosis in neuroblastoma cells effectively in vitro, which was accompanied with release of cytochrome c and Smac/DIABLO and caspases activation. Further studies indicated that gold(III) porphyrin 1a inhibited X-linked inhibitor of apoptosis (XIAP). However, we found that gold(III) porphyrin 1a can induce a survival signal, Akt activation within minutes and could last for at least 24 h. To further confirm association between activation of Akt and the effectiveness of gold(III) porphyrin 1a, neuroblastoma cells were treated with API-2, an Akt-specific inhibitor. API-2 sensitised cells to gold(III) porphyrin 1a-induced apoptosis and growth inhibition. CONCLUSION: These results suggested that Akt may be considered as a molecular 'brake' that neuroblastoma cells rely on to slow down gold(III) porphyrin 1a-induced apoptosis and antiproliferation. Gold(III) porphyrin 1a is a mitochondrial apoptotic stimulus but also activates Akt, suggesting an involvement of Akt in mediating the effectiveness to growth inhibition and apoptosis by gold(III) porphyrin 1a and that inhibition of Akt can enhance the anticancer activity of gold(III) porphyrin 1a in neuroblastoma.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Xie

Sun

et al. 2009

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…Some interesting hypotheses were made concerning the likely antiproliferative mechanisms of some gold compounds. Relevant changes in the expression of a number of proteins engaged in redox metabolism, stress response, in mitochondrial functions as well as in apoptosis pathways were detected [11,27]. In previous works we obtained proteomic results for the gold(III) compound Auoxo6 and Auranofin on A2780 cell line, either sensitive (A2780/S) or resistance (A2780/R) to cisplatin.…”

Section: Introductionmentioning

confidence: 99%

Proteomic analysis of A2780/S ovarian cancer cell response to the cytotoxic organogold(III) compound Aubipyc

Gamberi

Massai

Magherini

et al. 2014

Journal of Proteomics

View full text Add to dashboard Cite

Aubipy c is an organogold(III) compound endowed with encouraging anti-proliferative properties in vitro that is being evaluated pre-clinically as a prospective anticancer agent. A classical proteomic approach is exploited here to elucidate the mechanisms of its biological actions in A2780 human ovarian cancer cells. Based on 2-D gel electrophoresis separation and subsequent mass spectrometry identification, a considerable number of differentially expressed proteins were highlighted in A2780 cancer cells treated with Aubipy c . Bioinformatic analysis of the groups of up-regulated and down-regulated proteins pointed out that Aubipy c primarily perturbs mitochondrial processes and the glycolytic pathway. Notably, some major alterations in the glycolytic pathway were validated through Western blot and metabolic investigations. Biological significanceThis is the first proteomic analysis regarding Aubipy c cytotoxicity in A2780/S ovarian cancer cell line. Aubipy c is a promising gold(III) compound which manifests an appreciable cytotoxicity toward the cell line A2780, being able to overcome resistance to platinum. The proteomic study revealed for Aubipy c different cellular alterations with respect to cisplatin as well as to other gold compound such as auranofin. Remarkably, the bioinformatic analysis of proteomic data pointed out that Aubipy c treatment affected, directly or indirectly, several glycolytic enzymes. These data suggest a new mechanism of action for this gold drug and might have an impact on the use of gold-based drug in cancer treatment.

show abstract

“…Notably, one of these altered proteins was ezrin. In turn, Che et al [19] used 2D electrophoresis based proteomic technology to investigate the protein expression profiles of human nasopharyngeal carcinoma SUNE1 cells upon treatment with gold(III) porphyrin 1a [20]. Relevant changes in the expression of a number of proteins engaged in redox metabolism, in the mitochondrial functions, and in apoptosis pathways were detected.…”

Section: Introductionmentioning

confidence: 99%

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

et al. 2010

View full text Add to dashboard Cite

We have recently shown that a group of structurally diverse gold compounds are highly cytotoxic toward a panel of 36 human tumor cell lines through a variety of biochemical mechanisms. A classic proteomic approach is exploited here to gain deeper insight into those mechanisms. This investigation is focused on Auoxo6, a novel binuclear gold(III) complex, and auranofin, a clinically established gold(I) antiarthritic drug. First, the 72-h cytotoxicity profiles of Auoxo6 and auranofin were determined against A2780 human ovarian carcinoma cells. Subsequently, protein extraction from gold-treated A2780 cells sensitive to cisplatin and 2D gel electrophoresis separation were carried out according to established procedures. Notably, both metallodrugs caused relatively modest changes in protein expression in comparison with controls as only 11 out of approximately 1,300 monitored spots showed appreciable quantitative changes. Very remarkably, six altered proteins were in common between the two treatments. Eight altered proteins were identified by mass spectrometry; among them was ezrin, a protein associated with the cytoskeleton and involved in apoptosis. Interestingly, two altered proteins, i.e., peroxiredoxins 1 and 6, are known to play crucial roles in the cell redox metabolism. Increased cleavage of heterogeneous ribonucleoprotein H was also evidenced, consistent with caspase 3 activation. Overall, the results of the present proteomic study point out that the mode of action of Auoxo6 is strictly related to that of auranofin, that the induced changes in protein expression are limited and selective, that both gold compounds trigger caspase 3 activation and apoptosis, and that a few affected proteins are primarily involved in cell redox homeostasis.

show abstract

Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug

Cited by 82 publications

References 73 publications

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition

Proteomic analysis of A2780/S ovarian cancer cell response to the cytotoxic organogold(III) compound Aubipyc

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Contact Info

Product

Resources

About