Genistein Modulation of Immune-Associated Genes in LNCaP Prostate Cancer Cell Line

Abstract

Abstract:Background: Prostate cancer is the most common form of non-dermatologic cancer and the second leading cause of cancer deaths in the United States. Survival rate for the advanced disease still remains low, so current research is aimed at alternative or adjuvant treatments that will target components of the signal pathways in the progression of carcinogenesis with little or no cytotoxicity. In this study we investigated the effect of genistein on expression levels of genes involved in the immune response 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/genes 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 including MHC genes that are involved in immune recognition of cells and the DefB1 and the HLA membrane receptor genes involved in immunogenicity. Conclusion:The results of the study indicate that genistein inhibits carcinogenesis of LNCaP prostate cancer growth via regulation of the identified specific targets/pathways in immunogenicity/immune response. The results thus provide significant insight into the roles that genistein could play in immune response to prostate cancer proliferation and potential role in immunotherapy and/or adjuvant therapeutic regimen.

Anti-colorectal cancer effect of interleukin-2 and interferon-β fusion gene driven by carcinoembryonic antigen promoter

“… 4 Thus, therapy with immune-associated genes shows great potential advantages in the treatment of cancer. 5 , 6 Both interferon-β (IFN-β) and interleukin-2 (IL-2) are important cytokines and play multiple roles in host immune system. They are also shown to display remarkable antitumor potential.…”

Therapeutic Impact of Vitamin C on the Anticancer Activities of Genistein Isoflavone in Radiosensitized Lncap Prostate Cancer Cells

“…Genistein has been reported to induce cytotoxicity, inhibit cellular proliferation, and promote apoptotic cell death in various cancer cells in vivo and in vitro [11,12]. The anti-cancer effects of genistein has been demonstrated in many human cancers such as breast, lung, prostate, lymphoma, leukemia, and head and neck cancers [11,13] through many mechanisms that include: the inhibition of topoisomerase I & II [14], inhibition of telomerase activity [15], inhibition of tyrosine kinase signaling pathway, inhibition of cell survival proteins; Akt and NF-kβ [16] and anti-apoptotic proteins -Bcl-2 and Bcl-XL [17][18][19], and also the inhibition of angiogenesis [10]. Genistein has been shown to also display bipolar properties in which at low concentrations, it behaves as an antioxidant and at high concentration acts as a pro-oxidant [12].…”

Involvement of Caspase-3 Pathway in Anti-cancer Properties of Genistein in AGS Gastric Cancer Cell Line is Still Enigmatic

“…Even though anti-cancer drugs usually target tumor cells by inducing apoptosis, it has been demonstrated that most tumors are resistant to chemotherapy-induced apoptosis (23). Thus recent studies have focused on using new therapeutic agents -nutraceutical phytochemicals such as genistein, in particular -which have significantly lower cytotoxicity compared to chemotherapy medicines but still exhibit anti-cancer effects (9).…”

“…In spite of conducting extensive investigations into cancer and having considerable knowledge about its genomic basis, cancer still remains a serious threat to human life (9). Current protocols for treatment of the cancers rely on the use of synthetic and chemical drugs; due to their unpleasant side effects, however, recent studies have been mainly focusing on the use of natural products and herbal plant-derived medicines.…”