Oxidative stress plays a crucial role in the onset and development of prostate cancer [66–69]. It typically denotes the disruption between the production of reactive oxygen species and the antioxidant defenses, or the capability to oxidize beyond the existing antioxidant capacity. Reactive oxygen species (ROS) are characterized as unstable and highly reactive molecules, commonly existing as superoxide anion, hypochlorous acid, hydrogen peroxide, singlet oxygen, hypochlorite, hydroxyl radicals, and lipid peroxides, which are involved in cell processes such as growth, differentiation, and death [70]. Under physiological conditions, the human body has a solid antioxidant system, including antioxidant enzymes and some small molecules, the main antioxidant enzymes are phase II detoxifying enzymes: for example, glutathione S-transferase (GST), NAD (P)H quinone oxidoreductase(NQO), epoxide hydrolase, heme oxygenase 1 (HO-1), UDP-glucuronosyltransferases (UGT), superoxide dismutase (SOD), phase II detoxification enzymes are redox-sensitive stress-inducing proteins downstream of the Nrf2-Keap1 axis that reduces various oxidative stress and inflammation-derived cytotoxicity [71,72]. Numerous elements, both inherent to the cells (Nrf2 deficiency; DNA) and from the external environment (chronic; radiation), can result in elevated ROS generation in the prostate. Elevated levels of ROS can cause prostate dysfunction, which subsequently leads to even greater ROS production [73]. An antioxidant defense system, which can be enzymatic or non-enzymatic, helps to counteract and regulate the levels of reactive oxygen species (ROS) in order to sustain physiological homeostasis. Reducing ROS levels below the homeostatic threshold might disrupt both proliferation and the host defense mechanisms. Conversely, an accumulation of ROS in the prostate can disturb its normal functioning, resulting in a decreased antioxidant capacity by interfering with the Nrf2-antioxidant response element axis (ARE), increasing mitochondrial DNA (mtDNA) mutation and aggressive phenotypes, and causing DNA damage [73]. SFN is an antioxidant that, once in the cell from the blood, reacts spontaneously with glutathione and other thiols, enhancing the oxidative state of the cell and leading to a transient increase in reactive oxygen species. This change in oxidation status led to rapid activation of the Nrf2-antioxidant response element defense system (ARE), leading to increased transcription of many genes involved in restoring the redox state of cells and preventing ROS damage [74,75]. In homeostasis, Nrf2 is associated with cytoplasmic protein KEAP1, which is continuously ubiquitous by Cul3 E3 ubiquitin ligase and subsequently degraded by proteases. In the presence of oxidative stress, conformational changes KEAP1 can occur directly with Sulfhydryl KEAP1 or indirectly through changes in the cellular redox state, leading to Nrf2 separation from KEAP1, metastasis to the nucleus, heterogeneity with the small molecule myofascial fibrosarcoma (sMaf) protein, and binding to ARE, leading to a large number of gene transcription and antioxidant responses [76,77].

SFN activates Nrf2, leading to structural changes in KEAP1, disrupting the KEAP1-Nrf2 complex, blocking Nrf2 ubiquitination from being degraded, and promoting Nrf2 nuclear translocation [77], which enhances the expression of phase II detoxification enzymes GST, HO-1, and NQO-1, causing an enhanced antioxidant effect (Fig. 1). Excitingly, the effect of adding SFN to human prostate cells and the increased activity of phase II detoxification enzymes (GST, NQO1) after tube feeding of SFN in F-344 rats [72,78]. Significantly enhanced protein expression of Nrf2 and NOQ1 was similarly observed in transgenic adenocarcinoma mouse prostate (TRAMP)-C1 cell lines after SFN treatment [79].

It has been shown that ab initio synthesis of fatty acids is necessary for prostate cancer growth and that lipid metabolism and genes related to lipid metabolism can play an important role in the progression of prostate cancer through metabolic pathways and anti-apoptotic effects [80–83]. The key enzyme for fatty acid synthesis is fatty acid synthase (FASN), a 250–270 kDa cytoplasmic protein, and fatty acid synthase is involved in the final step in the ab initio synthesis of fatty acids (i.e., condensation of acetyl coenzyme-A and malonyl coenzyme-A to produce palmitate), which in turn generates more types of fatty acids, which undergo β-oxidation catalyzed by the key enzyme carnitine palmitoyltransferase 1A (CPT1A). It also plays an important function in energy homeostasis, converting excess carbon into fatty acid stores and supplying energy through β-oxidation when necessary. The mechanisms regulating the expression of fatty acid synthases are complex and not fully understood, and their expression and activity are regulated by growth factors, hormones, and dietary factors, among others [84]. The expression of FASN is low in most human tissues and high in liver and adipose tissue [85]. It has been shown that FASN gene expression is upregulated in approximately one-quarter of human prostate cancer patients [86]. Migita et al. showed that FASN overexpression leads to prostate intraepithelial neoplasia (PIN) progression [87]. However, the regulation of fatty acid synthase mechanisms is unknown, cytotoxicity can be produced on tumor cells through the use of FASN inhibitors [88], and because of this, FSAN is considered a potential new target for the treatment of many cancer cell line (22Rv1), Singh et al. found that SFN could reduce the protein and mRNA levels of acetyl-CoA carboxylase 1 (ACC1A), FASN and CPT1A, and the expression of FASN and ACC1A protein in TRAMP mouse model treated with SFN was also significantly reduced chemoprevention of prostate cancer is associated with the inhibition of fatty acid synthesis and its β-oxidation [59] (Fig. 2).

In normal cells, glucose undergoes initial metabolism to pyruvate within the cytoplasm; under aerobic circumstances, pyruvate is further converted to carbon dioxide through the process of oxidative phosphorylation (OXPHOS). In contrast, when oxygen is absent, pyruvate is transformed into lactate through glycolysis, thereby generating ATP [89]. In cancer cells, the energy supply comes mainly from aerobic glycolysis and tumor cells convert the major ATP pathway OXPHOS to aerobic glycolysis also known as the Warburg effect [89]. The conversion from glucose to lactate requires the involvement of several enzymes such as hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) [90]. In Singh et al.’s study, it was found that SFN significantly downregulated the expression of hexokinase 2 (HK2), pyruvate kinase M2 (PKM2) and/or lactate dehydrogenase A (LDHA) in mouse TRAMP model and prostate tumor lesions in Hi-Myc mice in-vitro and in-vivo, and significantly inhibited glycolysis in the prostate of Hi-Myc mice, reversing Warburg phenomenon in prostate cancer [60]. Warburg effect is considered to be a central component of tumor metabolic recoding and is mainly associated with overexpression of the transcription factor hypoxia-inducible factor HIF-1. HIF-1 is mainly composed of two subunits, HIF-1α and HIF-1β. Under normoxic conditions, HIF-1α is hydroxylated by proline and recognized with the Von Hippel-Lindau Disease Tumor Suppressor (pVHL) complex, which exhibits ubiquitin ligase activity that ubiquitinates HIF-1α, causing its degradation through the proteasomal pathway. Under hypoxic conditions, proline hydroxylation is inhibited, resulting in the accumulation of HIF-α translocated into the nucleus and HIF-1β forming a dimer with the hypoxia response elements (HREs) binding and recruitment of transcriptional co-activators (e.g., the histone acetyltransferases CBP/P300) thus obtaining complete transcriptional activity [91]. SFN can affect directly and/or indirectly affect glycolysis in prostate cancer (Fig. 2). Findings from a study conducted on the DU145 cell line related to human prostate cancer indicated that SFN may reduce the expression of HIF-1α induced by hypoxia by inhibiting the pathways of Jun N-terminal kinase (JNK) and extracellular regulated protein kinase (ERK) [92]. In addition, Carrasco et al. showed that SFN blocked androgen receptor agonist (androgen and Tip60)-induced glycolysis in human prostate cancer LNCaP cells, and that hexokinase and acetone kinase activities increased to reduce HIF-1α stability [93]. In addition, Myc genes can upregulate genes of the glycolytic pathway (HK2, LDHA) to enhance glucose metabolism [94], and one study reported SFN-mediated inhibition of c-Myc protein levels in human prostate cancer cell lines (LNCaP, PC-3, C4-2) and prostate adenocarcinoma of a Hi-Myc transgenic mouse(Myc-CaP cell line) [95].

Inflammation has a role in cancer in regulating the tumor microenvironment (TME) and promoting tumor proliferation and migration [96–99]. For example, the cytokine interleukin-6 (IL-6) can promote prostate cancer cell proliferation and inhibit apoptosis through a variety of cellular signaling pathways [100]. Nuclear transcription factor-κB (NF-κB) is an inducible protein transcription factor, mainly formed as a heterodimer by p50 and p65 of the Rel protein family. NF-κB can be activated by a variety of stimuli, such as tumor necrosis factor α (TNF-α), interleukin-1 (IL-1), lipopolysaccharide (LPS), ultraviolet (UV) and oxidative stress, etc. Activation of NF-κB by extracellular stimuli leads to phosphorylation, ubiquitination, and protein degradation of IκB kinase, which exposes the nuclear localization signal on NF-κB, resulting in nuclear translocation of the NF-κB complex and phosphorylation of p65. NF-κB regulates different inflammatory responses and immune responses and can also promote tumor progression by controlling tumor angiogenesis through upregulation of vascular endothelial growth factor (VEGF) and receptors [101,102], and Huang et al. have also shown that transfection of the highly metastatic prostate cancer cell line PC-3M with mutated IκBα (blocking NF-κB activity) injected into the prostate of nude mice revealed significant inhibition of major pro-angiogenic molecules such as VEGF, IL-8, and Matrix metalloproteinase 9 (MMP-9), as well as downregulation of MMP-9 mRNA and collagenase activity, and in general, blocking NF-κB signaling inhibited tumor invasion, angiogenesis, and metastasis [103]. In conclusion, NF-κB activation is common in cancer and is thought to be a key link between inflammation and cancer, with inflammatory factors in the tumor microenvironment again being the most common factors that enable NF-κB activation. Interestingly, SFN is known for its anti-inflammatory effects. Following stress, bacterial, viral, and pro-inflammatory cytokine-related cellular stimulation, IκB kinase is phosphorylated and then the kinase is degraded, which allows free translocation of NF-κB dimers into the nucleus and induces transcription of pro-inflammatory cytokines (IL-6, IL-10, TNF-α) [104]. It was shown that SFN could reduce inflammation by inhibiting the binding of NF-κB to DNA [105]. In addition, it has also been shown that SFN inhibits IκB kinase complex (IKK) phosphorylation in human prostate cancer PC-3 cells, specifically inhibiting IKKβ, leading to IKKβ-mediated inhibition of IκBα phosphorylation. This in turn leads to reduced ubiquitination and protein degradation of IκBα, with subsequent retention of NF-κB in the cytoplasm and reduced nuclear translocation of p65 and consequent attenuation of NF-κB-regulated VEGF, cyclin D1, and B-cell lymphoma/leukemia-2 protein X-linked (Bcl-XL) gene expression [106]. The stimulation of tumor cell proliferation, apoptosis, or mutations in cancer cells can be prompted by the activation of NF-κB and the subsequent cascade of inflammatory cytokines or chemokines [107]. Consequently, blocking the activation of NF-κB plays a crucial role in mitigating detrimental effects. SFN notably reduces the levels of several inflammatory mediators, including IL-6, IL-1β, TNF-α, nitric oxide (NO), and prostaglandin E2 (PGE2), along with inflammatory enzymes such as inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2), through the suppression of the NF-κB signaling pathway [61,105].

In addition, Toll-like receptors (TLR) are key pattern recognition receptors (PRR) that induce innate or adaptive immune responses, whereas TLR-4 is a key signaling receptor that triggers inflammation. LPS recognizes CD14/TLR-4/MD-2 heterotrimers and activates myeloid differentiation factor 88 (MyD88)-dependent pathways and TRIF (MyD88-independent pathway) to trigger inflammation.TLR4 activation also increases the expression of VEGF and transforming growth factor-β1 (TGF-β1) in prostate cancer cells, thus promoting tumor development [108]. It has been shown that SFN inhibits the TLR4/MyD88 pathway and reduces TNF-α and IL-6 levels [109]. In macrophages, HIF-1 can upregulate TLR4 expression, while SFN can inhibit hypoxia and CoCl₂-induced TLR4 expression upregulation by inhibiting phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) pathway and HIF-1α activation [110]. It has also been shown that the anti-inflammatory mechanism of action of SFN is closely related to the inhibition of TLR4 response by directly and indirectly targeting the TLR4-md2 receptor complex [111,112]. In addition, signal transducer and activator of transcription 3 (STAT-3) is closely associated with inflammation, and tumor promoters, lipopolysaccharide, and cigarette smoke can activate the STAT-3 signaling pathway, and STAT-3 binds competitively with NF-κB at overlapping DNA binding sites [113], and studies have shown that SFN reduces STAT-3 in the prostate cancer cell lines DU145 and LNCap expression [114]. In conclusion, SFN can inhibit pro-inflammatory factors through various targets to disrupt the tumor microenvironment in prostate cancer (Fig. 3).

Numerous experimental studies, both in vivo and in vitro, have demonstrated that SFN and its metabolites can inhibit cell proliferation and induce apoptosis in prostate cancer (Fig. 4). Induction of G2/M phase cell cycle arrest in SFN-treated human prostate cancer cell line (PC-3) involves checkpoint kinase 2 (ChK2) checkpoint activation leading to phosphorylation of cell division cycle 25C (cdc25C), resulting in its segregation in the cytoplasm [115]. SFN was also found to upregulate CD44 variants v4, v5, and v7 to slow down the proliferative activity of tumor cells in human prostate cancer cell lines (DU-145 and PC-3 cell lines) in-vitro, and also upregulate the tumor suppressor p19 in blocking cell cycle and apoptosis [116]. Administration of SFN in a PTEN gene-deficient mouse model reversed the effects of early prostate cancer development due to PTEN deficiency and served to inhibit cell proliferation [117].

Phosphorylated expression of AKT protein (cell cycle protein D1) was reduced after feeding high doses of broccoli sprouts in a TRAMP mouse model, thereby inhibiting cell proliferation [118]. SFN was also found to cause G2/M phase cell cycle arrest in wild-type LNCap cell lines, but not in its variant Rh-0 cells (mitochondrial DNA deletion), thus SFN causes G2/M phase cell cycle arrest in human prostate cancer cells due to mitochondria-derived ROS-mediated [119]. Moreover, telomerase consists of a complex of ribonucleoproteins in eukaryotes that includes six distinct subunits: heat shock protein 90, the human telomerase RNA component (hTERC), dyskerin, the telomerase-associated protein 1 (TEP1), p23, and the human telomerase reverse transcriptase (hTERT). The activity of the hTERT gene is absent in normal human cells; however, it is frequently expressed in different forms of cancers (such as:prostate cancer), signifying a necessary role in the unlimited proliferation of tumor cells [120]. It has been shown that SFN can inhibit hTERT expression in prostate cancer cells in two prostate cancer cell lines, LNCap and PC-3 [121].The apoptosis triggered by SFN is primarily facilitated through intrinsic mitochondrial pathways as well as extrinsic death receptors (DRs) mechanisms [122]. Intrinsic mitochondrial-mediated apoptosis begs the question of mitochondrial autophagy, a catabolic process in which the autophagic system targets damaged mitochondria and delivers them to lysosomes for degradation. Mitochondrial autophagy helps control the quality and quantity of mitochondria [123]. Mitochondrial autophagy is one of the organelle-specific autophagic pathways that are used to maintain cell structure and function [124]. Mitochondria are believed to be the primary location for the production of ROS, primarily via the electron transport chain and various localized proteins, and overproduction of ROS occurs when mitochondrial dysfunction occurs, and overproduction of ROS further damages mitochondria, creating a vicious cycle [125]. Excessive intracellular ROS production and imbalance of antioxidant capacity cause oxidative stress, which not only leads to mitochondrial dysfunction, but excessive accumulation of damaged mitochondria may lead to apoptosis. In turn, mitochondrial autophagy and tumor cell suppression are closely related [126].

Extrinsic death receptors mainly include Tumor necrosis factor-related apoptosis-inducing ligand 1 (TNFR1), Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand 1 (TRAIL1) receptors (DR-4, DR-5), and Fas (Apo-1; CD95) mediated [122]. Research indicates that the cell death induced by SFN in human prostate cancer cells is attributed to the generation of ROS. This ROS production triggered by SFN is associated with a disruption of the mitochondrial membrane potential, which in turn facilitates the release of cytochrome C from the mitochondria into the cytoplasm. This process culminates in the activation of caspase 9, ultimately resulting in cell death [127]. It has also been reported that in human prostate cancer cell line PC-3, SFN-induced apoptosis is associated with upregulation of B-cell lymphoma-2 Associated X Protein (Bax), downregulation of B-cell lymphoma-2 Bcl-2) and activation of caspase-3, caspase-8 and caspase-9. SFN causes upregulation of the pro-apoptotic protein Bax and downregulation of the anti-apoptotic protein Bcl-2 in the Bcl-2 protein family will lead to an increase in the Bax to Bcl-2 ratio, making activation of the mitochondrial pathway for cytochrome c release, which activates caspase-9; and then caspase-8 and caspase-9 activate caspase 3 to shear the DNA repair enzyme PARP, leading to apoptosis [128]. In addition, research involving mouse embryonic fibroblasts (MEFs) revealed that SFN plays a role in triggering caspase activation, which in turn facilitates apoptosis by enhancing the expression of Apoptotic protease activating factor (Apaf) and decreasing levels of X-linked inhibitor of apoptosis protein (XIAP) [129].

In addition, in BPH1, PC3 and LNCap prostate cancer cells, SFN induced apoptosis by inhibiting HDAC activity, inducing cell cycle arrest through upregulation of mRNA and protein levels of p21 and Bax, and activating caspase [130]. Hahm et al. in DU145 and LNCap human prostate cancer cell lines found that SFN induced apoptosis by inhibiting IL-6/JAK2/STAT3 signaling pathway to promote apoptosis [114]. It has also been shown in DU-145 and PC-3 cells that the SFN metabolites SFN-cysteine (SFN-Cys) and SFN-N-acetylcysteine (SFN-NAC) cause apoptosis by activation of caspase 3 and induction of protein kinase 1/2 (ERK1/2) phosphorylation, resulting in downregulation of α-microtubulin [131]. SFN was found to activate p38 Mitogen-activated protein kinase (p38MAPK), JNK leading to apoptosis in a PC-3 prostate cancer cell line [132]. In studies on androgen-independent prostate cancer cell lines (PC-3, DU145) and androgen-dependent prostate cancer cell lines (VcaP), SFN was found to have cytotoxic and pro-apoptotic effects on prostate cancer cell lines [62].

Prostate cancer initially develops in a manner dependent on androgens, driven by the signaling pathway of the androgen receptor (AR), which is critical not only for normal prostate development and physiological function, but also for the proliferation, survival, invasion, and clonogenic capacity of PCa cells [133–135]. SFN has been shown to reduce AR protein in LNCap and C4-2 cell lines by inhibiting transcription of androgen receptor mRNA, leading to Ser210/213 phosphorylation and reduced total androgen receptor [64] and increasing proteasomal degradation of androgen receptor protein [136]. SFN was shown in LNCap cells and Vcap cells to increase HSP90 acetylation and lead to AR and HSP90 dissociation by inhibiting HDAC6 activity in cells, decreasing AR protein levels and reducing AR target gene expression [136]. In 22Rv1 cell line (a CRPC cell line expressing AR-FL and multiple AR splice variants), it was demonstrated that SFN can reduce AR-FL and AR-V7 levels, and this reduction in AR protein levels may result in diminished cell proliferation, migration and cloning capacity [137]. SFN was found to reduce AR protein levels through AR protein degradation and inhibition of AR gene expression in androgen-dependent cell lines (LNCap) and androgen-independent cell lines (C4-2B) [138]. Another interesting study in a TRAMP mouse model found that SFN treatment with Nrf2 levels similar to ADT treatment reduced ROS levels in prostate cancer cells and caused prostate cancer cells to show similar sensitivity to radiotherapy as with ADT treatment [139].

In epigenetics, histone modifications, DNA methylation, RNA regulation and nucleosome remodeling are considered to be important influential mechanisms that are dysregulated in cancer [140–142], as well as in prostate cancer [143–145]. Modifications of histones include acetylation, methylation, phosphorylation, and ubiquitination, among which histone acetylation plays the most prominent role. Histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs) are in balance in normal cells, and when histone acetyltransferase expression is decreased and/or histone deacetyltransferase expression is increased is closely related to the process of tumorigenesis and progression, while SFN inhibits histone deacetylases (HDACs), histone deacetylase (HDAC) overexpression will lead to histone deacetylation, and deacetylation causes DNA to wrap around histones too tightly, thus inhibiting gene expression, which may lead to cancer development if the affected genes are oncogenes [146]. Zhang et al. treating TRAMP-C1 cell lines with 1.0, 2.5 μM SFN respectively found that SFN decreased HDAC1, HDAC4, HDAC5, HDAC7 proteins were reduced in a dose-dependent manner [79]. SFN inhibited the epigenetic regulator HDAC3 in PC-3 cells and decreased HDAC3 expression in TRAMP mice [147]. In prostate cancer cells PC3 and LnCap, as well as in BPH1, SFN similarly suppressed HDAC activity, which resulted in heightened global histone acetylation. This enhancement promoted the interaction between acetylated histone H4 and the P21 and Bax promoters, leading to an upregulation of both mRNA and protein levels of p21 and Bax [130].

DNA methylation occurs mainly at cytosine residues of cytosine-phosphate-guanine (CpG) dinucleotides and is regulated by DNA methylation transferase, and DNA hypermethylation leads to gene silencing. In prostate cancer, overall hypomethylation of tumor-associated genes and site-specific hypermethylation influence tumorigenesis and progression [148], with hypomethylation associated with genomic instability, transposons, and proto-oncogene activation, and hypermethylation can silence genes involved in cancer protection, with targets including those involved in DNA repair, detoxification, and apoptosis [148]. In previous studies treating TRAMP-C1 cell lines with 1.0 and 2.5 μM SFN respectively found that SFN reduced the protein levels of DNMT1 and DNMT3a in DNA methylation transferase (DNMT) in a dose-dependent manner [79]. It was also shown that SFN treatment of LNCap cell lines inhibited DNMT1 and DNMT3b expression, and SFN treatment of benign prostatic hyperplasia cells (BPH-1) and PC-3 cells significantly inhibited DNMT1 and DNMT3a mRNA expression, while protein expression only showed a downward trend. The expression of cell cycle protein D2 mRNA increased after SFN treatment in LNCap cell lines, which served to inhibit prostate cancer growth [149]. Furthermore, SFN in both LNCap and PC-3 prostate cancer cell lines by regulating and reversing aberrant promoter DNA methylation in chemokine-related gene targets in cancer cells [150].

Long non-coding RNAs (lncRNAs) are closely associated with prostate cancer development and progression [151,152]. Treatment with SFN in a study of LNCap and PC-3 cell lines was found to inhibit the expression of the long non-coding RNA (lncRNA) LINC01116 [65].

In addition to the above pathways through which SFN inhibits prostate cancer, it has been found that the SFN metabolite SFN-Cys causes sustained phosphorylation of ERK1/2 and triggers downregulation of galectin-1 (an invasion-associated protein) in DU145 and PC-3 cells, which in turn inhibits invasion [153]. SFN inhibits invasion by regulating E-calcine mucin (an invasion inhibitor), CD44v6 (invasion promoter) and MMP-2 (invasion promoter) to inhibit invasion [154]. In the advancement of lung metastasis, by diminishing cell proliferation and boosting the lytic activity of NK cells [155].

Singh et al. found that SFN treatment of TRAMP mice led to increased IL-12 production by dendritic cells. This effect leads to increased cytotoxicity of NK cells to prostate cancer cell lines, and improves the activation efficiency of dendritic cells with cytotoxic function of NK cells after co-culture. Aside from the effects observed in-vitro regarding NK cells and dendritic cells due to SFN administration, researchers noted a rise in T cell infiltration in the prostate tumors of TRAMP mice treated with SFN when contrasted with control mice. This research demonstrates that SFN has the potential to boost the immune response in prostate tumors by prompting dendritic cells to secrete IL-12, which leads to heightened NK cell cytotoxicity and, consequently, an increase in T cell presence within prostate tumors, ultimately contributing to a decrease in tumor burden and metastasis [155]. As we described earlier that the c-Myc gene is associated with cancer stem cells in addition to glycolysis [156], SFN also inhibits c-Myc protein levels to impair prostate cancer stem cell (pCSC) capacity in LNCaP, PC-3 and Myc-CaP cells [95]. It has also been observed in PC-3 cell lines that SFN inhibits protein synthesis and is accompanied by a reduction in mTOR substrate phosphorylation [157].