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The effects of phenoxodiol on the cell cycle of prostate cancer cell lines.

Mahoney S, Arfuso F, Millward M, Dharmarajan A - Cancer Cell Int. (2014)

Bottom Line: Prostate cancer is associated with a poor survival rate.The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes.These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Perth, WA 6009 Australia.

ABSTRACT

Background: Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes.

Methods: Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30 μM) for 24 and 48 h. The expression of cell cycle genes p21(WAF1), c-Myc, Cyclin-D1, and Ki-67 was investigated by Real Time PCR.

Results: Here we report that phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the upregulation of p21(WAF1) in all the cell lines in response to treatment, indicating that activation of p21(WAF1) and subsequent cell arrest was occurring via a p53 independent manner, with induction of cytotoxicity independent of caspase activation. We found that c-Myc and Cyclin-D1 expression was not consistently altered across all cell lines but Ki-67 signalling expression was decreased in line with the cell cycle arrest.

Conclusions: Phenoxodiol demonstrates an ability in prostate cancer cells to induce significant cytotoxicity in cells by interacting with p21(WAF1) and inducing cell cycle arrest irrespective of p53 status or caspase pathway interactions. These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer.

No MeSH data available.


Related in: MedlinePlus

cyclin-d1mRNA expression analysis of prostate cancer cells over 24 and 48 hours post phenoxodiol treatment.
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Fig5: cyclin-d1mRNA expression analysis of prostate cancer cells over 24 and 48 hours post phenoxodiol treatment.

Mentions: Cyclin-D1 is recognised as potent initiator of cell cycle progression from G1 through to S phase by the Cyclin-D1 Cdk4 complex activating the Cyclin E Cdk2 complex, which results in inhibition of the cell cycle inhibiting Rb protein [13]. Figure 5 demonstrates the quantitative mRNA expression of the cell cycle regulator gene Cyclin-D1 over 24 and 48 hours post phenoxodiol treatment in prostate cancer cells. Decreasing Cyclin-D1 expression, in response to phenoxodiol treatment, could result in quiescent and apoptotically sensitive cells. LNCaP cells did not have a detectable change in Cyclin-D1 expression level under the influence of phenoxodiol treatment. DU145 cells were found to have a significant decrease in the expression of Cyclin-D1 versus DMSO vehicle control (p = 0.0071) after 24 hours of treatment with 30 μM phenoxodiol no other changes in expression were detected in the DU145 cell line. PC3 cells exhibited a similar trend to treatment as the DU145 cells, with both the 10 μM phenoxodiol (p = 0.026) and 30 μM phenoxodiol (p = 0.0011) treatments significantly decreased in expression versus DMSO vehicle control after a 24 hour period of treatment.Figure 5


The effects of phenoxodiol on the cell cycle of prostate cancer cell lines.

Mahoney S, Arfuso F, Millward M, Dharmarajan A - Cancer Cell Int. (2014)

cyclin-d1mRNA expression analysis of prostate cancer cells over 24 and 48 hours post phenoxodiol treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4231195&req=5

Fig5: cyclin-d1mRNA expression analysis of prostate cancer cells over 24 and 48 hours post phenoxodiol treatment.
Mentions: Cyclin-D1 is recognised as potent initiator of cell cycle progression from G1 through to S phase by the Cyclin-D1 Cdk4 complex activating the Cyclin E Cdk2 complex, which results in inhibition of the cell cycle inhibiting Rb protein [13]. Figure 5 demonstrates the quantitative mRNA expression of the cell cycle regulator gene Cyclin-D1 over 24 and 48 hours post phenoxodiol treatment in prostate cancer cells. Decreasing Cyclin-D1 expression, in response to phenoxodiol treatment, could result in quiescent and apoptotically sensitive cells. LNCaP cells did not have a detectable change in Cyclin-D1 expression level under the influence of phenoxodiol treatment. DU145 cells were found to have a significant decrease in the expression of Cyclin-D1 versus DMSO vehicle control (p = 0.0071) after 24 hours of treatment with 30 μM phenoxodiol no other changes in expression were detected in the DU145 cell line. PC3 cells exhibited a similar trend to treatment as the DU145 cells, with both the 10 μM phenoxodiol (p = 0.026) and 30 μM phenoxodiol (p = 0.0011) treatments significantly decreased in expression versus DMSO vehicle control after a 24 hour period of treatment.Figure 5

Bottom Line: Prostate cancer is associated with a poor survival rate.The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes.These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer.

View Article: PubMed Central - PubMed

Affiliation: School of Anatomy, Physiology and Human Biology, Faculty of Science, The University of Western Australia, Crawley, Perth, WA 6009 Australia.

ABSTRACT

Background: Prostate cancer is associated with a poor survival rate. The ability of cancer cells to evade apoptosis and exhibit limitless replication potential allows for progression of cancer from a benign to a metastatic phenotype. The aim of this study was to investigate in vitro the effect of the isoflavone phenoxodiol on the expression of cell cycle genes.

Methods: Three prostate cancer cell lines-LNCaP, DU145, and PC3 were cultured in vitro, and then treated with phenoxodiol (10 μM and 30 μM) for 24 and 48 h. The expression of cell cycle genes p21(WAF1), c-Myc, Cyclin-D1, and Ki-67 was investigated by Real Time PCR.

Results: Here we report that phenoxodiol induces cell cycle arrest in the G1/S phase of the cell cycle, with the resultant arrest due to the upregulation of p21(WAF1) in all the cell lines in response to treatment, indicating that activation of p21(WAF1) and subsequent cell arrest was occurring via a p53 independent manner, with induction of cytotoxicity independent of caspase activation. We found that c-Myc and Cyclin-D1 expression was not consistently altered across all cell lines but Ki-67 signalling expression was decreased in line with the cell cycle arrest.

Conclusions: Phenoxodiol demonstrates an ability in prostate cancer cells to induce significant cytotoxicity in cells by interacting with p21(WAF1) and inducing cell cycle arrest irrespective of p53 status or caspase pathway interactions. These data indicate that phenoxodiol would be effective as a potential future treatment modality for both hormone sensitive and hormone refractory prostate cancer.

No MeSH data available.


Related in: MedlinePlus