Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells

McPherson, R. A.; Galettis, Peter; Souza, Paul L. de

doi:10.1038/sj.bjc.6604920

Cited by 18 publications

(10 citation statements)

References 35 publications

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“…These findings demonstrate that Phenoxodiol is potently active against androgen‐resistant DU145 and PC3 cells, which are considered to be more aggressive metastatic cell lines than LNCaP cells. A recent report has also reported that Phenoxodiol inhibits cell‐growth in PC3 and DU145 cells 34. These findings support our cell‐cycle data showing that Phenoxodiol‐induced G1 arrest in these two cell lines.…”

Section: Discussionsupporting

confidence: 92%

“…Although several studies indicate that Phenoxodiol may be a good chemosensitizer 27,34,35, a Phase II study have shown that patients with hormone‐refractory prostate cancer had better responses to higher doses and long‐term treatment with Phenoxodiol as monotherapy (400 mg every 8 hr for 21 consecutive days) 29. A recent study is also reported that Phenoxodiol provides a significant anti‐cancer effect as a monotherapy in patients with hormone‐refractory prostate cancer (HRPC) at dosages of 200 and 400 mg in 28‐day cycles 36.…”

Section: Discussionmentioning

confidence: 99%

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Phenoxodiol inhibits growth of metastatic prostate cancer cells

Aguero

Venero

Brown³

et al. 2010

The Prostate

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These data demonstrated that Phenoxodiol promotes apoptosis, as determined by PARP-1 degradation, via mitochondrial depolarization and G1/S cell-cycle arrest thereby confirming that it is active against androgen-dependent and independent prostate cancer cells. Although a precise target for Phenoxodiol has not been identified, these data contribute to our understanding of the mechanism by which this drug promotes cell death in prostate cancer cells, and warrants the continued clinical development of Phenoxodiol as a therapeutic for the treatment of metastatic prostate cancer.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Phenoxodiol inhibits growth of metastatic prostate cancer cells

Aguero

Venero

Brown³

et al. 2010

The Prostate

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“…However, conjugated linoleic acid and a soy protein isolate were found to increase the growth of prostate cancer cell lines in a mouse model 43 . Phenoxodiol in combination with cisplatin has been shown to be synergistic against DU145 cells and probably additive in PC3 cells 54 …”

Section: Combinations Of Isoflavones and Other Drugsmentioning

confidence: 99%

“…43 Phenoxodiol in combination with cisplatin has been shown to be synergistic against DU145 cells and probably additive in PC3 cells. 54 In vivo combination therapy of soy isoflavones and radiation for prostate cancer has also been investigated, with favorable effects on the control of the disease. 48,55 Interestingly, pure genistein increased the incidence of para-aortic nodal metastases in this orthotopic mouse model.…”

Section: Combinations Of Isoflavones and Other Drugsmentioning

confidence: 99%

Clinical pharmacology of isoflavones and its relevance for potential prevention of prostate cancer

Souza

Russell²,

Kearsley

et al. 2010

Nutrition Reviews

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Isoflavones are phytoestrogens that have pleiotropic effects in a wide variety of cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, including prostate cancer cells. Epidemiological studies have raised the hypothesis that isoflavones may play an important role in the prevention and modulation of prostate cancer growth. Since randomized phase III trials of isoflavones in prostate cancer prevention are currently lacking, the best evidence for this concept is presently provided by case control studies. However, in vitro data are much more convincing in regard to the activity of a number of isoflavones, and have led to the development of genistein and phenoxodiol in the clinic as potential treatments for cancer. In addition, the potential activity of isoflavones in combination with cytotoxics or radiotherapy warrants further investigation. This review focuses on the clinical pharmacology of isoflavones and its relevance to their development for use in the prevention of prostate cancer, and it evaluates some of the conflicting data in the literature.

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“…Flavonoids genistein, quercetin, silibinin, and fisetin are known to augment effects of chemotherapeutic agents (12)(13)(14). A combination of phenoxodiol, an analogue of isoflavone genistein (15), together with carboplatin has entered phase-III clinical trials for the treatment of ovarian cancer (http://www.OVATUREtrial.com). The above reports suggest the importance of exploring and improving flavonoid combinations for cancer treatment.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Activity of a Combination of Cisplatin and Fisetin in Embryonal Carcinoma Cells and Xenograft Tumors

Tripathi

Samadder

Gupta

et al. 2011

Molecular Cancer Therapeutics

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Use of chemotherapeutic drug cisplatin is limited because of its toxicity. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin to reduce its effective treatment dose. This study evaluates the potential of fisetin, a flavonoid, to increase cisplatin cytotoxicity in human embryonal carcinoma NT2/D1 cells. Addition of fisetin to cisplatin enhanced cisplatin cytoxicity in vitro at four times lower dose than that required by cisplatin monotherapy for similar cytotoxic effects. Cisplatin, fisetin monotherapy, and addition of fisetin to cisplatin in a combination increased FasL expression. Cisplatin and fisetin as single agents activated caspases-8 and -3 and caspases-9 and -7, respectively, whereas combination treatment activated all 4 caspases. Increases in p53 and p21 and decreases in cyclin B1 and survivin occurred, all effects being more exaggerated with the combination. Fisetin, with or without cisplatin, increased expression of proapoptotic protein Bak and induced its mitochondrial oligomerization. Bid truncation and mitochondrial translocation of Bid and p53 was induced by fisetin in the presence or absence of cisplatin. Downregulation of p53 by short hairpin RNA during drug treatment decreased p21 levels but caused survivin increase, thus reducing cell death. Upstream to p53, inhibition of p38 phosphorylation reduced p53 phosphorylation and cell death. In a NT2/D1 mouse xenograft model, combination therapy was most effective in reducing tumor size. In summary, findings of this study suggest that addition of fisetin to cisplatin activates both the mitochondrial and the cell death receptor pathway and could be a promising regimen for the elimination of embryonal carcinoma cells. Mol Cancer Ther; 10(2); 255-68. Ó2011 AACR.

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Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells

Cited by 18 publications

References 35 publications

Phenoxodiol inhibits growth of metastatic prostate cancer cells

Phenoxodiol inhibits growth of metastatic prostate cancer cells

Clinical pharmacology of isoflavones and its relevance for potential prevention of prostate cancer

Anticancer Activity of a Combination of Cisplatin and Fisetin in Embryonal Carcinoma Cells and Xenograft Tumors

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