# Anticancer Effects of Seaweed-Derived Bioactive Compounds
## 6 Mono-, Sesqui-, and Diterpenes  
Terpenoids have been shown to inhibit the growth of a variety of cancer cells, including leukemia, breast cancer, prostate cancer, pancreatic cancer, skin cancer, and colon cancers [67, 68, 69]. For more than two decades, several terpen from seaweeds have been investigated as anticancer compounds with relevant cytotoxic activities against various cancer cell lines. Figure 4 shows examples of seaweed terpenoids. The cytotoxicity of meronorsesquiterpenes (cystoazorones A [30] and B [31]) and two new meroditerpenes (cystoazorol A and B) isolated from _Cystoseira abies-marina_ were evaluated in HeLa cells. Cystoazorol A (**32**) was three times more potent than cystoazorone A when comparing the IC\({}_{50}\) value [70].  
The diterpenoids (**33-36** and **37**) isolated from the Mediterranean brown algae _Dilophus ligulatus_ showed interesting cytotoxic activity against murine leukemia cells (p-388) and p-388 doxorubicin-resistant cells with IC50 3.64-13.3 uM and IC\({}_{50}\) 5.95-12.9 uM, respectively [71]. Flabellinol (**38**) and flabellinone (**39**) isolated from _S. flabelliforme_ possessed  
Figure 3: Structures of seaweed carotenoids.  
two polycyclic fused oxidized rings that exhibited cytotoxicity against NCI-H460 cells (IC\({}_{50}\) 9 uM and 14 uM, respectively) by blocking the cellular sodium channel activity [72]. Two cyclic meroditerpenoids, atomarianone A (**40**) and atomarianone B (**41**), which are analogs of flabellinone (**39**), were isolated from the brown algae _Taonia atomaria_ in the Aegean Sea. This previous study is the second report on metabolites with a functionalized indane moiety instead of a benzofurano- or a benzopyrano-ring connecting their aromatic and diterpenoid parts. Both metabolites exhibited significant cytotoxic activity against two lung cancer cell lines (NSCLC-N6 and A549) [73].  
Red algae of the genus _Laurencia_ in tropical oceans are known to have highly diverse secondary metabolites, especially terpenoids and acetogenins [74,75]. Some of these metabolites, including laurebiphenyl (**42**), dehydromoepiaplysinol (**43**), dehydromoelysin (**44**), and isoasplysin (**46**), exhibited cytotoxic effects against various types of cancer cell lines [76,77]. In particular, dehydromoelysin (**45**) and isoaplysin (**46**) are sesquiterpenes with different structures, with C3a-hydroxyl and C3a-bromomethyl groups. Debromoaplysin (**44**) showed more selective toxicity to cancer cell lines than isoaplysin (**46**) [77]. Meanwhile, dehydromoepiaplysinol (**43**) and debromoaplysinol (**45**) are epimers because of the difference in the stereochemistry at the C3 chiral center. The chiral center plays a pivotal role in the drug-receptor interaction. Therefore, debromoepiaplysinol (**43**) is less active than debromoaplysin (**44**).  
The monoterpenes (**47**-**52**) isolated from the macroalga _Pocaminium subrii_ collected from South Africa were identified as halogenated compounds. The halogenated monoterpenes showed strong cytotoxic effects on esophageal cancer cell lines (WHCO1) with an IC\({}_{50}\) value in the range of 6.6-15.1 uM [78].  
Figure 4: Chemical structures of terpenoids isolated from seaweeds.  
The seaweed diterpenoid 14-keto-stypodiol diacetate (**53**), isolated from _Stypopodium flabelliforme_, showed cytotoxic effects on the prostate cancer cell line DU-145 with an IC\({}_{50}\) of 24 uM. This compound exhibited a clear mechanism of microtubule assembly inhibition, which can cause mitotic arrest and inhibitory effects on cell invasion [79]. However, the molecular mechanisms of many marine natural products are not clear because of their lower activity.