The Effects of Phenoxodiol on the Cell Cycle of Prostate Cancer Cell Lines

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2014 Nov 18

PMID 25400509

Citations 9

Authors

Simon Mahoney

Frank Arfuso

Michael Millward

Arun Dharmarajan

Affiliations

Soon will be listed here.

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.

Citing Articles

POU Class 2 Homeobox Associating Factor 1, as a Hub Candidate Gene in OP, Relieves Osteoblast Apoptosis.

Wang X, Zou C, Hou C, Li M, Bian Z, Zhu L Appl Biochem Biotechnol. 2024; 196(9):6072-6096.

PMID: 38183606 DOI: 10.1007/s12010-023-04833-y.

Rescuing Nucleus Pulposus Cells From Senescence via Dual-Functional Greigite Nanozyme to Alleviate Intervertebral Disc Degeneration.

Shi Y, Li H, Chu D, Lin W, Wang X, Wu Y Adv Sci (Weinh). 2023; 10(25):e2300988.

PMID: 37400370 PMC: 10477883. DOI: 10.1002/advs.202300988.

The role of isoflavones in augmenting the effects of radiotherapy.

Ivashkevich A Front Oncol. 2023; 12:800562.

PMID: 36936272 PMC: 10016616. DOI: 10.3389/fonc.2022.800562.

Monooxygenase-catalyzed regioselective hydroxylation for the synthesis of hydroxyequols.

Hashimoto T, Nozawa D, Mukai K, Matsuyama A, Kuramochi K, Furuya T RSC Adv. 2022; 9(38):21826-21830.

PMID: 35518870 PMC: 9066559. DOI: 10.1039/c9ra03913a.

Phenoxodiol sensitizes metastatic colorectal cancer cells to 5-fluorouracil- and oxaliplatin-induced apoptosis through intrinsic pathway.

Yaylaci E, Onen H, Saglam A EXCLI J. 2020; 19:936-949.

PMID: 32665777 PMC: 7355152. DOI: 10.17179/excli2020-2042.

References

Canfield S, Zhu K, Williams S, McConkey D . Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells. Mol Cancer Ther. 2006; 5(8):2043-50. DOI: 10.1158/1535-7163.MCT-05-0437. View

Cooper S . Reappraisal of serum starvation, the restriction point, G0, and G1 phase arrest points. FASEB J. 2003; 17(3):333-40. DOI: 10.1096/fj.02-0352rev. View

Maclachlan T, Sang N, Giordano A . Cyclins, cyclin-dependent kinases and cdk inhibitors: implications in cell cycle control and cancer. Crit Rev Eukaryot Gene Expr. 1995; 5(2):127-56. DOI: 10.1615/critreveukargeneexpr.v5.i2.20. View

Srivastava R, Chen Q, Siddiqui I, Sarva K, Shankar S . Linkage of curcumin-induced cell cycle arrest and apoptosis by cyclin-dependent kinase inhibitor p21(/WAF1/CIP1). Cell Cycle. 2007; 6(23):2953-61. DOI: 10.4161/cc.6.23.4951. View

Fu M, Wang C, Li Z, Sakamaki T, Pestell R . Minireview: Cyclin D1: normal and abnormal functions. Endocrinology. 2004; 145(12):5439-47. DOI: 10.1210/en.2004-0959. View

Ahmad I, Patel R, Liu Y, Singh L, Taketo M, Wu X . Ras mutation cooperates with β-catenin activation to drive bladder tumourigenesis. Cell Death Dis. 2011; 2:e124. PMC: 3101820. DOI: 10.1038/cddis.2011.7. View

Senderowicz A . Targeting cell cycle and apoptosis for the treatment of human malignancies. Curr Opin Cell Biol. 2004; 16(6):670-8. DOI: 10.1016/j.ceb.2004.09.014. View

Michaud L, Valero V, Hortobagyi G . Risks and benefits of taxanes in breast and ovarian cancer. Drug Saf. 2000; 23(5):401-28. DOI: 10.2165/00002018-200023050-00005. View

Roy S, Singh R, Agarwal C, Siriwardana S, Sclafani R, Agarwal R . Downregulation of both p21/Cip1 and p27/Kip1 produces a more aggressive prostate cancer phenotype. Cell Cycle. 2008; 7(12):1828-35. PMC: 2744498. DOI: 10.4161/cc.7.12.6024. View

10.

Xie W, He Y, Huo D, Huang Y, Wu W . A mimic of phosphorylated prolactin inhibits human breast cancer cell proliferation via upregulation of p21 waf1. Med Oncol. 2009; 27(4):1340-5. DOI: 10.1007/s12032-009-9386-6. View

11.

Roy S, Kaur M, Agarwal C, Tecklenburg M, Sclafani R, Agarwal R . p21 and p27 induction by silibinin is essential for its cell cycle arrest effect in prostate carcinoma cells. Mol Cancer Ther. 2007; 6(10):2696-707. DOI: 10.1158/1535-7163.MCT-07-0104. View

12.

Aguero M, Venero M, Brown D, Smulson M, Espinoza L . Phenoxodiol inhibits growth of metastatic prostate cancer cells. Prostate. 2010; 70(11):1211-21. DOI: 10.1002/pros.21156. View

13.

Mahoney S, Arfuso F, Rogers P, Hisheh S, Brown D, Millward M . Cytotoxic effects of the novel isoflavone, phenoxodiol, on prostate cancer cell lines. J Biosci. 2012; 37(1):73-84. DOI: 10.1007/s12038-011-9170-6. View

14.

Hanahan D, Weinberg R . The hallmarks of cancer. Cell. 2000; 100(1):57-70. DOI: 10.1016/s0092-8674(00)81683-9. View

15.

Koda M, Sulkowska M, Kanczuga-Koda L, Tomaszewski J, Kucharczuk W, Lesniewicz T . The effect of chemotherapy on Ki-67, Bcl-2 and Bak expression in primary tumors and lymph node metastases of breast cancer. Oncol Rep. 2007; 18(1):113-9. View

16.

El-Deiry W, Tokino T, Velculescu V, Levy D, Parsons R, Trent J . WAF1, a potential mediator of p53 tumor suppression. Cell. 1993; 75(4):817-25. DOI: 10.1016/0092-8674(93)90500-p. View

17.

Devlin H, Mack P, Burich R, Gumerlock P, Kung H, Mudryj M . Impairment of the DNA repair and growth arrest pathways by p53R2 silencing enhances DNA damage-induced apoptosis in a p53-dependent manner in prostate cancer cells. Mol Cancer Res. 2008; 6(5):808-18. DOI: 10.1158/1541-7786.MCR-07-2027. View

18.

Madani S, Ameli S, Khazaei S, Kanani M, Izadi B . Frequency of Ki-67 (MIB-1) and P53 expressions among patients with prostate cancer. Indian J Pathol Microbiol. 2012; 54(4):688-91. DOI: 10.4103/0377-4929.91492. View

19.

Seo Y, Kim B, Chun S, Park Y, Kang K, Kwon T . Apoptotic effects of genistein, biochanin-A and apigenin on LNCaP and PC-3 cells by p21 through transcriptional inhibition of polo-like kinase-1. J Korean Med Sci. 2011; 26(11):1489-94. PMC: 3207053. DOI: 10.3346/jkms.2011.26.11.1489. View

20.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View