# Anticancer Effects of Seaweed-Derived Bioactive Compounds
## 4 Phenolic Compounds  
Phenolic compounds are a large family of natural organic compounds found in land plants and seaweeds. Polyphenols are known as radical scavengers that improve endogenous antioxidant properties [30; 31]. Seaweed polyphenols possess multiple phenolic units. Many seaweeds generate polyphenols as secondary metabolites, and polyphenols have beneficial effects, including antioxidant, antiviral, antimicrobial, and anticancer effects [32; 33]. Seaweeds are a valuable source of polyphenolic compounds, such as phlorotannins, bromophenols, flavonoids, phenolic terpenoids, and mycosporine-like amino acids. Various biological activities are related to the interaction of polyphenolic compounds with various cellular receptors, transcription factors, and enzymes [34; 35; 36]. Phlorotannins are composed of phloroglucinol (1,3,5-tri-hydroxy benzene) (**7**) and are found in brown algae, such as kelps, rockweeds, and _Sargassacean_ species, and in red algae in low amounts [37; 38; 39; 40]. Phlorotannins are classified into six major groups (Table 2) [41]. Dieckol (**14**) isolated from the brown algae _Ecklonia cava_ inhibited PANC-1 cell growth by inducing apoptosis. The induction of apoptosis and the expression of apoptotic proteins, such as Bax and Bcl-2, were further analyzed using Western blot [42]. Dieckol (**14**) also inhibited the proliferation and migration of non-small-cell lung cancer by regulating the PI3K/AKT signaling pathway [43]. Moreover, at a concentration of 84.3 ug/mL and 99.6 ug/mL, dieckol (**14**) inhibited A2780 ovarian carcinoma and SKOV3 cells, respectively [11; 44]. The phlorotannin-rich fraction (100 ug/mL) isolated from _Laminaria japonica_ showed 30% and 43% inhibitory effects against BEL-7402 human hepatocellular carcinoma cells and P388 murine leukemic cells, respectively [45]. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Group** & **Chemical Name** & **Structure** \\ \hline Monomeric unit & Phloroglucinol (**7**) & \\ \hline Fucol & Trifucol (**8**) & \\ \hline Phlorethol & Tetraphorethol (**9**) & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Structures of phloroglucinol and six major groups of phlorotannins. Adapted from [41]. Figure 2 shows structures of phenolic compounds. The 8,8-bieckol (**15**), 6,6-bieckol (**16**), and 6,8-bieckol (**17**) have been isolated from several brown algae; however, their anticancer activities have not yet been reported. Phloroglucinol isolated from _Eckonia cava_ decreased the cell viability of and induced apoptosis in HT-29 cells by altering Bcl-2 family proteins, cytochrome c release, and activation of caspase-3 and caspase-8 [46]. Furthermore, phloroglucinol decreased CD44 (+) cancer cells and cancer stem cell regulators, including sox2, CD44, Oct4, Notch2, and \(\beta\)-catenin [47]. Furthermore, phloroglucinol increased the sensitivity of breast cancer cells to anticancer drugs, such as cisplatin, doxorubicin, and taxol. Phloroglucinol regulates the maintenance of breast cancer stem-like cells (BCSCs) by inhibiting Kirsten rat sarcoma virus (KRAS) and its downstream regulators of the PI3K/AKT and RAF-1/ERK signaling pathway [47]. \begin{table}
\begin{tabular}{c c c} \hline
**Group** & **Chemical Name** & **Structure** \\ \hline \hline \multirow{2}{*}{Fucophilorethol} & \multirow{2}{*}{Fucodiphorethol (**10**)} & \multirow{2}{*}{\
\begin{tabular}{c} HO, OH \\ HO, OH \\ OH \\ \end{tabular} } & \multirow{2}{*}{
\begin{tabular}{c} OH, OH \\ OH \\ \end{tabular} } \\ \cline{1-1}  & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Cont. Bromophenol (BP) compounds are secondary metabolites of marine algae, which have benzene rings attached to substituents, such as hydroxyl and bromine. Many studies have demonstrated the anti-tumor properties of marine BP by using different in vitro and in vivo tumor models.