# Phytosterols in Seaweeds: An Overview on Biosynthesis to Biomedical Applications
## 4 Health Benefits and Biomedical Applications of Phytosterols
### Phytosterols as Anticancer Agents
Similarly, treatment with brassicaterol also dramatically reduced the expression levels of 5-\(\alpha\)-reductase type 2 (5-\(\alpha\)-R2) and AR, compared with the cancer-induced rats. According to these findings, brassicaterol inhibits bladder carcinogenesis by acting on cell cycle-associated signaling and androgen signaling via several mechanisms [128]. \(\beta\)-Sitosterol treatment caused DNA fragmentation and tailing in the COLO 320 DM human colon cancer cell line. In COLO 320 DM cells, it also resulted in the production of free radicals. In vitro, \(\beta\)-sitosterol treatment dramatically reduced \(\beta\)-catenin and PCNA expression in COLO 320 DM cells. Similarly, in vivo, \(\beta\)-sitosterol treatment for 16 weeks significantly reduced the number of aberrant crypts and crypt multiplicity in DMH-treated rats [129]. At 48 h, \(\beta\)-sitosterol significantly inhibited cancer cell proliferation in MDA-MB-231 cells. It triggered G0/G1 arrest, as shown by lower levels of CDK4 and cyclin D1 proteins and higher levels of p21/Cip1 and p27/Kip1 proteins. Apoptotic activation was also confirmed by Bcl-2 downregulation and Bax upregulation. The depolarization of mitochondrial membrane potentials is caused by \(\beta\)-sitosterol-induced apoptosis [130]. The cytotoxic effects of seaweed-derived compounds pertaining to anticancer activity are listed in Table 2.  
The effects of \(\beta\)-sitosterol on A549 cells was significant, with concentration- and time-dependent action. \(\beta\)-sitosterol-treated Swiss albino mice were healthy and showed no significant changes in behavior or mortality rate. A549 cells treated with \(\beta\)-sitosterol showed nuclear and DNA fragmentation with apoptotic morphological changes. \(\beta\)-sitosterol treatment caused the decreased expression of Bcl-2 and upregulated the expression of Bax protein; it also resulted in the cleavage of caspase-3 and PARP protein. \(\beta\)-sitosterol induced mitochondrial membrane depolarization and released cytochrome c, which confirmed that the mode of apoptosis induced by \(\beta\)-sitosterol in A549 cells was intrinsic. Furthermore, when cells were treated with \(\beta\)-sitosterol, the number of cells in the G2/M phase was increased [131]. The effect of \(\beta\)-sitosterol in A549 cells was mediated by elevated ROS, which was confirmed by the pretreatment of NAC. In cancer cells elevated levels of thioredoxin (Trx1) and thioredoxin reductase (TrxR1) play a role in ROS homeostasis [132]. \(\beta\)-sitosterol decreased the expression of both TrxR1 and Trx1 in A549 cells thereby causing oxidative stress and intrinsic mode of cancer cell death [133]. \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Seaweed Names** & **Cell Lines Used** & \begin{tabular}{c} **Therapeutic** \\ **Compounds** \\ \end{tabular}  & **Anticancer Activity** & **References** \\ \hline _Ulca fasciata_, & human breast & palmitic acid, oleic acid, & & \\ _Ulva lactuca_, _Amphira_ & adenocarcinoma & retinoic acid, & & \\ _ancys_, _Cornallina_ & line (MCF-7) and & dihydroactinidiolide, & & \\ _mediterranean_, and & colorectal carcinoma & thiosemicbarazide, & & \\ _Sargassum filipendula_ & cell line (HCT-116) & disobutyl phthalate, & & \\ _Sargassum spp._ & \begin{tabular}{c} SMMC-7721, Huh7, \\ and HCCLM3 liver \\ \end{tabular}  & \ \begin{tabular}{c} fucoidan \\ \end{tabular}  & \begin{tabular}{c} deactivates the integrin \\ \(\alpha\)V\(\beta\)3/SRC/E2F1 \\ signaling pathway; \\ \end{tabular}  & [135] \\ \hline _Ulva lactuca, Codium_ & & & & \\ _tomentosum_, _Cystoseira_ & human colorectal & & \\ _crinita_, _Cystoseira stricta_, & carcinoma (Caco2) and & polyphenols and & human colorectal \\ _Sargassum vulgar,_ & human corneal & flavonoids & carcinoma & \\ _Gelidin latifolium_, & epithelial cells (HCEC) & & & \\ _Hypnea musciformis_ and & & & & \\ _Jania rubens_ & & & & \\ \hline _Ecklonia maxima_ & HeLa, H157 and MCF7 & phlorotannins and & & \\ _Sargassum spp.,_ & breast cancer (MCF-7) & & & \\ _Turbinaria spp.