Cyanidin-3-O-[178,179]. prostate cancer prevention and treatment. roots[62]gingerol fresh/driedin the cytoplasm with the formation of the apoptosome and activation of executioner caspases [147]. The proposed mechanisms contributing to the circumvention of apoptosis and induction of malignancy may include impaired cell death receptor activity, defects in tumor suppressor gene into the cytoplasm, decreased the levels of anti-apoptotic proteins Bcl-2 and Bcl-2-extra-large (Bcl-XL) proteins, and Tead4 increased the level of Bax [150]. Moreover, the apoptotic processes produced by apigenin have been demonstrated by Dapivirine induction of the elevated levels of TNF-related apoptosis-inducing ligand (TRAIL) and Dapivirine death receptor 5 (DR5) in prostate cancer cells [150,151]. In addition, apigenin upregulated the level of caspase-3 and -8 in cancer stem cells isolated from androgen-negative prostate cancer cells [82]. Cyanidin-3-O-[178,179]. However, their protection can be interrupted by a loss of heterozygosity mutation [178]. Apigenin stabilizes tumor suppressor protein p53 by phosphorylation of alternate frame reading protein Dapivirine (p14ARF) and upregulation of p27 protein in prostate cancer cells [125,150]. It was reported that curcumin increased the expression level of p53 in prostate cancer cells from lung metastasis in a mouse model [119], while EGCG increased the levels of p53 and p21 in a dose- and time-dependent manner in androgen-dependent prostate cancer cells [154]. 2.5.3. DNA Methylation and Histone ModificationEpigenetic mechanisms involve the modification in the gene status by activating or silencing the transcription, without changes in the DNA sequence [180]. The phenomenon is extremely complex due to the high diversity of genomic DNA [181]. However, the major biochemical mechanisms related to epigenetic modifications might be summarized as methylation, acetylation, phosphorylation, or ubiquitination [180,181]. Hypomethylation is correlated with genome instability, activation of transposons and proto-oncogenes, while hypermethylation might silence genes involved in anticancer mechanisms, such as tumor suppressor genes or genes involved in promoting apoptosis or cell cycle arrest [182]. For instance, in prostate cancer the transposable elements Alu (DNA sequence first identified with restriction endonuclease isolated from gene methylationLNCaP, PC-3 cell lines[185,186] miRNA EGCGoncogenic miR-21
tumor suppressor miR-330LNCaP, 22Rv1 cell lines[113] Genisteinoncogenic miR-151
tumor suppressor miR-574-3pLNCaP, PC-3, DU-145 PCa cell lines
RWPE-1 non-malignant epithelial prostate cell line[73] Resveratroloncogenic miR-21Highly invasive PC-3M-MM2, DU-145, LNCaP cell lines [79] Open in a separate window Legend: ROS, reactive oxygen species; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; GSR, glutathione reductase; EGCG, epigallocatechin gallate; AR, androgen receptor; HSP90, heat shock protein 90; IGF-1, insulin-like growth factor 1; EGFR, epidermal growth factor receptor; HER2, receptor tyrosine kinase ErbB2/v-ErbB2 avian erithroblastic leukemia viral homolog 2; CXCL-1, -2, chemokine with CXC motif ligand -1, -2; c-Met/HGF, hepatocyte growth factor; PI3K, phosphatidylinositol 3-kinase; Akt, Ak tymoma protein/PKB, protein kinase B; ERK 1/2, extracelluar signal-regulated kinases -1, -2; FoxO, forkhead box O protein; NF-B, nuclear factor kappa-light-chain-enhancer of activated B cells; mTOR, mammalian target of rapamacyn; GSK-3, glycogen synthase kinase; PDK1, phosphoinositide-dependent kinase-1; IB, inhibitor of NF-B; SOS, son of sevenless; GRB2, growth factor receptor-bound protein 2; PKC, protein kinase C, JNK, c-Jun N-terminal kinase; MAPK, mitogen activated protein kinase; MRP1, multidrug resistance-associated protein 2; PTEN, phosphatase and tensin homolog; cdc25, cell cycle division protein 25; CHK1, checkpoint kinase 1; caspase-3, cysteine-aspartic acid protease 3; m, mitochondrial membrane potential; Bcl-2, B-cell lymphoma type 2 protein; Bcl-XL, Bcl-2 extralarge protein; Bax,.