# Phytosterols in Seaweeds: An Overview on Biosynthesis to Biomedical Applications
## 4 Health Benefits and Biomedical Applications of Phytosterols
### Phytosterols as Anticancer Agents  
Foods enriched with phytosterols and their oxy- derivatives could help to prevent tumor growth in humans. Phytosterols play various roles in the human body to control the progression of the numerous cancer types [116]. In gastric cancer cells (SNU-1), stigmasterol induces mitochondrial-mediated apoptosis, through which it suppresses cancer development. The activation of the apoptotic pathway by stigmasterol was evidenced by increased Bax and decreased Bcl-2 expression. In a concentration-dependent manner, it also reduced cancer cell migration and caused G2/M cell cycle arrest. In addition, stigmasterol suppresses the JAK/STAT signaling pathway, which is thought to be responsible for its anticancer effect in SNU-1 cells [117]. In Swiss albino mice, the effect of stigmasterol on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was examined. In the stigmasterol-treated groups, the tumor size and the total number of papillomas were decreased. Meanwhile, GSH, SOD, and catalase activity were all elevated in the skin of stigmasterol-treated mice. Furthermore, stigmasterol treatment dramatically reduced high levels of lipid peroxide and DNA damage in the control group. This implied that stigmasterol protected against DMBA-induced genotoxicity by acting as an antigenotoxic and antioxidant [118]. In a time- and dose-dependent way, stigmasterol dramatically reduced the viability of gastric cancer cell lines, such as SGC-7901 and MGC-803. Changes in the expression of the apoptotic key proteins Bax and Bcl-2, the cleavage of caspase-3, and poly (ADP-ribose) polymerase (PARP) have indicated apoptotic-mediated cell death upon treatment with stigmasterol in both cell lines [119]. LC3-II acts as a marker for an autophagic activity [120]. Treatment with stigmasterol resulted in an increase in LC3-II levels, indicating the activation of autophagy. Similarly, beclin 1 is an upstream molecule that is essential for autophagosome formation and that plays a key role in autophagy induction [121]. The expression of beclin-1 was also enhanced upon stigmasterol treatment, which further confirmed autophagy activation (Figure 5). As a result, stigmasterol's anti  
formation, and the formation of vessel branches [123]. Campesterol has been shown to reduce bFGF-induced pathological angiogenesis in HUVEC endothelial cells. The CAM assay confirmed that campesterol significantly hindered the creation of new embryonic blood vessels without impacting the established vasculature [124]. Brassicasterol treatment has been found to reduce the viability of LNCaP and PC-3 cells. It reduced the number of LNCaP cells and suppressed the expression of prostate-specific antigen and androgen receptors. Also, brassicasterol caused sub-G1 phase arrest. The expression of PARP was inhibited by brassicaterol treatment, during which induced cleaved caspase-3 expression was noted. Brassicaterol inhibits cell migration in LNCaP cells, as well [125]. Furthermore, it inhibited n-butyl-(4-hydroxybutyl) nitrosamine (BHBN) and SS-induced carcinogenesis. Cyclin D1 has been found to be overexpressed in bladder epithelial cells and it is a key player in the cell cycle [126]. When compared to the carcinogenesis group, the expression levels of cyclin D1, c-fos, and c-jun were significantly lower in brassicaterol-treated mice. This indicates the occurrence of cell cycle arrest. Prostaglandin E2 (PGE2), which is produced by the enzyme cyclooxygenase-2 (COX-2), also plays a role in the development of bladder cancer [127]. Brassicaterol treatment significantly reduced the expression of COX-2 in rats with comparison to the cancer-induced rats. Testosterone has a key role in bladder cancer development, while 5-\(\alpha\)-reductase converts testosterone to the active metabolite dihydrotestosterone (DHT). DHT has androgenic properties because it interacts with the nuclear androgen receptor (AR). When rats treated with brassicaterol were compared to cancer-induced rats, the expression level of 5-\(\alpha\)-R1 was considerably lower.