Molecular basis of the anti-cancer effects of genistein isoflavone in LNCaP prostate cancer cells

Abstract

Background: Prostate cancer is the most common form of non-skin cancer within the United States and the second leading cause of cancer deaths. Survival rates for the advanced disease remain relatively low, and conventional treatments may be accompanied by significant side effects. As a result, current research is aimed at alternative or adjuvant treatments that will target components of the signal transduction, cell-cycle and apoptosis pathways, to induce cell death with little or no toxic side effects to the patient. In this study, we investigated the effect of genistein isoflavone, a soy derivative, on expression levels of genes involved in these pathways. The mechanism of genistein-induced cell death was also investigated. The chemosensitivity of the LNCaP prostate cancer cells to genistein was investigated using ATP and MTS assays, and a caspase binding assay was used to determine apoptosis induction. Several molecular targets were determined using cDNA microarray and RT-PCR analysis.Results: The overall data revealed that genistein induces cell death in a time- and dose-dependent manner, and regulates expression levels of several genes involved in carcinogenesis and immunity. Several cell-cycle genes were down-regulated, including the mitotic kinesins, cyclins and cyclin-dependent kinases. Various members of the Bcl-2 family of apoptotic proteins were also affected. The DefB1 and the HLA membrane receptor genes involved in immunogenicity were also up-regulated. Conclusion: The results indicate that genistein inhibits growth of the hormone-dependent prostate cancer cells, LNCaP, via apoptosis induction through regulation of some of the genes involved in carcinogenesis of many tumors, and immunogenicity. This study augments the potential phytotherapeutic and immunotherapeutic significance of genistein isoflavone. Key words: Genistein isoflavone, prostate cancer, expression of genes, phytotherapeutic adjuvant, immunotherapy and chemotherapy

Genistein inhibits DNA methylation and increases expression of tumor suppressor genes in human breast cancer cells

“…It may be explained by that folic acid as a methyl donor can directly increase the methylation (Billington et al, 2013). Another study has found that there was no significant change in the SERPINB5 expression when 50 mM of genistein was given to treat LNCap prostate cancer cell line (Merchant et al, 2011). In our study, the SER-PINB5 mRNA expression was found to be significantly increased only after treatment with 100 mM geinstein in MCF-7 cells, but not in MDA-MB-231.…”

“…The result indicates that genistein at the concentration of 60 and 100 μM can reduce the methylation level of the ATM promoters and increase its mRNA expression. Ouyang et al () also found that ATM can be phosphorylated and activated in cancer cells treated with genistein. Additionally, further investigations, including the action side of ATM demethylation and whether the mutation of the action side can activate downstream DNA repair related proteins need to be studied.…”

Biochemical and Molecular Investigation of In Vitro Antioxidant and Anticancer Activity Spectrum of Crude Extracts of Willow Leaves Salix safsaf

“…Results reported here also revealed that F3 exhibits cytoprotective properties against oxidative stress (OS) mediated by the ROS molecule H 2 O 2 in normal untransformed WISH cells ( Figure 6 A–C). Reports by our group and other researchers revealed that plant extracts and their active principles usually exhibit potent antioxidant capacities that accompany its anticancer potentials [ 26 , 28 , 29 , 30 , 45 , 56 , 57 , 58 , 59 ]. OS is a pathogenetic biochemical phenomenon that is frequently linked to numerous pathological conditions and diseases, including cardiovascular, neurodegenerative diseases, diabetes mellitus , cancer and aging [ 60 ].…”

A review of molecular mechanisms involved in anticancer and antiangiogenic effects of natural polyphenolic compounds

“…This isoflavone reduces the risk of both hormone‐dependent and hormone‐independent cancers, including prostate, breast, gastric, colon, nonsmall cell lung cancers, and also leukemia (Lee, Kim, & Song, ). Genistein has been reported to exert its antitumor effects through its multitargeted biological activities (Merchant et al, ). This phytoestrogen induces apoptosis and G2/M phase cell cycle arrest in cancer cells (Z. Zhang et al, ).…”