Anticancer potential of algae-derived metabolites: recent updates and breakthroughs

Sharma, Ritu; Mondal, Arijit Sankar; Trivedi, Nitin

doi:10.1186/s43094-023-00492-2

Future Journal of Pharmaceutical Sciences

Table 2 List of compounds with anticancer properties derived from various macroalgae

From: Anticancer potential of algae-derived metabolites: recent updates and breakthroughs

Seaweed	Compound/extract	Class of compound	Type of cancer	Model/cell line	In vitro/in vivo	Activity	Signaling	Effect	Dose	References
Green seaweeds
Caulerpa racemosa Ulva lactuca	Seaweed hydrolysates extracted by subcritical water extraction	Phenolic and flavonoids	Abelson leukemia virus infected BALB/c mice macrophage	RAW 264.7	In vitro	Antioxidant	ROS scavenging ability	Total antioxidant = 8.03 mg/g Total antioxidant = 11.82 mg/g	50 μg/ml	[199]
Caulerpa racemosa var. macrophysa	Methanol extract	Phenolic and flavonoids	Hepatoma Human cervical adenocarcinoma	Huh-7 HeLa	In vitro	Anti-proliferative and ROS production	Downregulation of the CDC2 gene and upregulation of BAX occurred in both the cell lines. However, Cas-3 was upregulated only in Huh-7 and p53 gene was induced in HeLa only	ROS inhibition (42%) ROS inhibition (56%)	EC₅₀ = 23 μg/ml (24 h) EC₅₀ = 130 μg/ml (24 h)	[200]
Caulerpa scalpelliformis	Methanol extract	Phenolic and flavonoids	Human hepatoma Human cervical adenocarcinoma	Huh-7 HeLa	In vitro	Anti-proliferative and ROS production	CDC2 gene and Cas-3 was downregulated and BAX was upregulated in both the cell lines. However, the p53 gene was only upregulated in HeLa cells	ROS inhibition (54%) ROS inhibition (30%)	EC₅₀ = 140 μg/ml (24 h) EC₅₀ = 200 μg/ml (24 h)	[200]
Ulva lactuca	–	Polysaccharide	Mouse ascetic hepatoma	H22-bearing mice	In vivo	Anti-proliferative	Stimulating the expression of p53 and BAX/Bcl-2 ratio, reducing the expression of P13K/AKT/mTOR pathway, and inhibiting TRAF/TNF-α and CD31/VEGF	Tumor growth inhibition = 74.41%	0.3 ml of 300 mg/kg ULP	[201]
Chaetomorpha sp.	Ethanol extract	Terpenes	Breast cancer	MDA-MB-231	In vitro	Anti-proliferative and radical scavenging	NF-κB signaling and mitochondrial pyruvate dehydrogenase kinase enzyme was inhibited	–-	Anti-proliferative: IC₅₀ value = 225.18 μg/ml Antioxidant: IC₅₀ value = 9.41 μg/ml	[202]
Udotea flabellum	Sulfated galactans	Sulfated polysaccharide fractions F-I and F-II	Murine melanoma	B16-F10	In vitro	Anti-adhesive, anti-migratory, and anti-proliferative on fibronectin-coated surface	Inhibits adhesion and proliferation by binding to fibronectin in extracellular matrix with fibronectin being its molecular target	Anti-adhesive = ~ 50% Anti-migratory = ~ 50% Anti-proliferative = ~ 40%	Conc. = 1 μg/ml Conc. = 0.1 μg/ml Conc. = 1 μg/ml	[203]
Caulerpa cupressoides var. flabellata	––	Sulfated polysaccharide fractions CCB-F0.5 and CCB-F1.0	Murine Melanoma	B16-F10	In vitro	Anti-migratory, anti-proliferative, and melanin production inhibition	Interferes in primordial stage of cancer development. Melanin production is inhibited either by reducing the expression levels of melanogenic factors or through antioxidant activity	Inhibit cell colony formation = 80–90% Anti-migratory effect = 40–75% Inhibits melanin production = ~ 20%	1000 μg/ml	[204]
Enteromorpha compressa	Aqueous extract	–	Ehlrich ascites carcinoma	EAC	In vitro	Apoptosis	Induction of mitochondria-dependent apoptotic program	–	IC₅₀ = 95.35 μg/ml	[205]
Codium decorticatum	Glycoprotein	Polysaccharide	Breast cancer Cervical carcinoma Lung cancer	MCF-7 Siha A549	In vitro	Apoptosis	Cytotoxic to cancer cells by inducing cell membrane damage and releasing LDH enzyme	–	IC₅₀ = 45 μg/ml (48 h) IC₅₀ = 50 μg/ml (48 h) IC₅₀ = 40 μg/ml (48 h)	[206]
Ulva lactuca	–	Polysaccharide	Breast cancer	DMBA administered Wister rats MCF-7	In vivo In vitro	Apoptosis and anti-proliferative Cytotoxicity	Inhibits anti-apoptotic marker and bcl2 expression and elevates the level of pro-apoptotic and p53 protein	Normal duct, lobuloalveolar units, and acini with cuboidal epithelium lining Survival % of MCF-7 = ~ 60%	Single-dose of 25 mg/kg body weight of DMBA and 50 mg/kg body weight of ulvan polysaccharide every other day for 10 weeks IC₅₀ = 224.716 μg/ml	[106]
Ulva fasciata Delile	Guai-2-en-10α-ol	Terpene	Triple-negative breast cancer	MDA-MB-231	In vitro	Anti-proliferative	Downregulation of EGFR inhibited the functioning of key proteins of EGFR/P13K/Akt pathway and cell cycle arrest in G1 phase was also observed	Inhibition = 55–60%	IC₅₀ = 17.35 μM (24 h)	[207]
Ulva lactuca	Water extract	Polysaccharide	Hepatocellular carcinoma Human breast cancer Cervical cancer	HepG2 MCF-7 HeLa	In vitro	Cytotoxicity	May be due to low cell reactivity to Ulex europaeus-1 lectins	Cell viability = 0% for all the three cell lines at 100 μg/ml	IC₅₀ = 29.67 μg/ml IC₅₀ = 25.09 μg/ml IC₅₀ = 36.33 μg/ml	[147]
Gayralia oxysperma	Sulfated heterorhamnans	Sulfated polysaccharide fractions: OX OXS OXSb OXSc	Human glioblastoma	U87MG	In vitro	Cytotoxicity and cell cycle arrest	Increase in cell number in G₁ phase and mRNA expression levels of p53 and p21	Reduction in cell viability = 48.4% Reduction in cell viability = 46.1% Reduction in cell viability = 26.6% Reduction in cell viability = 28%	100 μg/ml for 48 h	[208]
Ulva intestinalis	–	Sulfated polysaccharide	Human hepatoma	HepG2	In vitro	Apoptosis	Induce the mitochondrial/caspase apoptotic pathway by enhancing the expression of Bax, cleaved caspase-3/-9, PARP, decreasing the expression of Bcl-2, loss of mitochondrial membrane potential, and cytochrome c release	Apoptotic cells = 30.2% (100 μg/ml) Apoptotic cells = ~ 40% (200 μg/ml) Apoptotic cells = 62% (400 μg/ml)	IC₅₀ = 98.5 μg/ml	[149]
Codium decorticatum	Glycoprotein	Polysaccharide	Breast cancer	MDA-MB-231	In vitro	Apoptosis	Induction of ROS dependent mitochondrial intrinsic apoptotic pathway by enhancing the Bax/Bcl-2 ratio, caspase-3/-9 cascade, loss of mitochondrial membrane potential, and cytochrome c release. In addition, the cell cycle gets arrested at the G₂/M phase, and the production of ROS increases	Apoptotic cells = ~ 60% ROS generation = 62%	IC₅₀ = 55 μg/ml (24 h)	[209]
Ulva fasciata	Methanolic extract	–	Human cervical adenocarcinoma Human breast carcinoma (estrogen positive) Human breast carcinoma (estrogen negative) Human hepatocellular carcinoma Human colon carcinoma	HeLa MCF-7 MDA-MB-231 HepG2 HT-29	In vitro	Cytotoxicity and apoptosis	Number of cells increased in Sub-G₁ phase	–	At 72 h: IC₅₀ = 54 μg/ml (72 h) IC₅₀ = 33 μg/ml (72 h) IC₅₀ = 84 μg/ml (72 h) IC₅₀ = 100 μg/ml (72 h) IC₅₀ = 400 μg/ml	[210]
Capsosiphon fulvescens	Glycoprotein	Polysaccharide	Human gastric carcinoma	AGS	In vitro	Anti-proliferative, anti-migratory, and apoptosis	Inhibits TGF-β1-activated FAK/P13K/AKT pathways, thereby downregulating integrin expression	Anti-proliferative = 50% Apoptotic = 42.68%	At 24 h: Anti-proliferative = 20 μg/ml Apoptotic = 20 μg/ml Anti-migratory = 20 μg/ml	[211]
Capsosiphon fulvescens	Glycoprotein	Polysaccharide	Human gastric carcinoma	AGS	In vitro	Anti-adhesive, anti-migratory, and apoptosis	Inhibits Wnt-1 signaling, β-catenin, and transcription factors. Additionally, cell cycle arrest was observed in G₀/G₁ phase	Cell cycle arrest = 73.1%	Cell cycle arrest = 20 μg/ml (24 h)	[212]
Red seaweeds
–	3,6-anhydro- l-galactose	Agar-derived sugar	Human colon cancer	HCT-116	In vitro	Anti-proliferative, and apoptosis	Induction of cell viability and apoptosis. Apoptosis was induced by reducing the level of Bcl-2 and enhancing Bax expression, caspase-3, caspase-9, p53, and PARP	Cell viability ~ 10%	100 μg/ml (72 h)	[213]
Gelidium latifolium	Ethanolic extract	–	Murine melanoma	B16-F10	In vitro	Anti-proliferative, cytotoxicity and induction of apoptosis	Mitochondria-mediated intrinsic pathway was promoted for apoptosis with increasing p53, Bax, Bak expression and decreasing Bcl2 expression	Apoptotic cells = 66.83%	IC₅₀ = 84.29 μg/ml	[214]
Pyropia yezoensis	Galactan fractions: GPY_crude GPY₃₀₀ GPY₁₀ GPY₁₀	Sulfated polysaccharide	Human prostate cancer	DU145 PC-3	In vitro	Anti-proliferative	Increases ROS generation, expression of Bax, initiator caspase-8 and -9, and executor caspase-3; targets P13K/AKT/mTOR pathway	Loss cell viability = 64% Loss cell viability = 68% Growth inhibition = 80% (750 μg/ml) Growth inhibition = 73% (750 μg/ml)	IC₅₀ = 100 μg/ml	[215]
Pyropia yezoensis Sookwawon 124	Gamma irradiated PYSP at doses 20 and 100 kGy: PYSP-20 PYSP-100	Polysaccharide	Breast cancer Human cervical adenocarcinoma Liver cancer	MDA-MB-231 HeLa Hep3B	In vitro	Anti-proliferative	mRNA expression levels of cyclin B1 and Cdk1 was downregulated while that of P53 and P21 was upregulated	Inhibition %: PYSP-20 ~ 45% PYSP-100 ~ 37% PYSP ~ 50% PYSP-20 ~ 50% PYSP-100 ~ 49% PYSP ~ 53% PYSP-20 ~ 47% PYSP-100 ~ 53%	Conc. = 200 μg/ml (48 h)	[216]
Pyropia yezoensis Chonsoo2	Native and Gamma irradiated PYP at doses 20 and 50: PYP PYP-20 PYP-50	Porphyran	Human cervical adenocarcinoma Breast cancer Liver cancer	HeLa MDA-MB-231 Hep3B	In vitro	Anti-proliferative and arrests G2/M phase	Cyclin B1 and Cdk1 had lower levels of mRNA expression while P53 and P21 had higher amounts	Inhibition %: PYP = 75% PYP-20 = ~ 50% PYP-50 = ~ 50% PYP-20 = ~ 41% PYP-50 = ~ 43% PYP = ~ 80% PYP-20 = 40% PYP-50 = 25%	Conc. = 200 μg/ml (48 h)	[217]
Chondrus armatus	Native carrageenan: κ-carrageenan λ-carrageenan Degraded carrageenan: κ-carrageenan λ-carrageenan	Polysaccharide	Human esophageal adenocarcinoma Squamous cell carcinoma	FLO1 KYSE30	In vitro	Antimetabolic	Induces anti-inflammatory cytokine (IL-10) and mediates TLR pathway (λ-carrageenan) or TLR-independent pathway (κ-carrageenan)	FLO1: Reduction in metabolic activity = 83.3–100.8% Reduction in metabolic activity = 79.1–80% KYSE30: Reduction in metabolic activity = 47–52.5% Reduction in metabolic activity = 55.1–56.2% FLO1: Reduction in metabolic activity = 31.2–57.8% Reduction in metabolic activity = 55.7–74.1% KYSE30: Reduction in metabolic activity = 62.3–64.6% Reduction in metabolic activity = 64.3–76.8%	Conc = 400 μg/ml (24 h)	[218]
Laurencia obtusa	–	Sulfated polysaccharide	Acute monocytic leukemia	THP-1	In vitro	Apoptosis	Immunostimulation of certain immune cells (NK cells, T and B cells, macrophages) and pro-inflammatory cytokines	Apoptosis = 98.1% (200 μg/ml)	EC₅₀ = 53 μg/ml	[150]
Hypnea musciformis	κ-carrabiose	Polysaccharide	Murine mammary adenocarcinoma Human ovarian cancer Myelogenous leukemia Mouse melanoma Mouse bladder cancer Human lung cancer Murine cutaneous squamous cell carcinoma	LM2 IGROV-1 K562 B16-F10 MB49 A549 Pam212	In vitro	Cytotoxicity and anti-migratory	Induction of the arrest of G2/M phase and apoptosis	Migration index = 0.52 (0.05 mg/ml) At 0.06 mg/ml, sub-G1 populations increased to 21.3% and an arrest in S phase increased to 13.6% in LM2 cells	At 48 h: IC₅₀ = 0.043 mg/ml IC₅₀ = 0.099 mg/ml IC₅₀ = 0.049 mg/ml IC₅₀ = 0.039 mg/ml IC₅₀ = 0.045 mg/ml IC₅₀ = 0.066 mg/ml IC₅₀ = 0.051 mg/ml	[219]
Palisada perforate (formerly known as Laurencia papillosa)	κ-carrageenan (LP-W1) ι-carrageenan (LP-W2) λ-carrageenan (LP-W3)	Sulfated polysaccharide	Human breast cancer	MCF-7	In vitro	Apoptosis	Reduction in cell viability by increasing apoptotic activity and induction of ACTIVE-CASPASE-3, PARP, Bax gene and p53 gene	At 72 h: Cell viability = 51.8% Cell viability = 18.4% Early apoptosis = 26% Late apoptosis = 30% Cell viability = 22.7% Early apoptotis = 7% Late apoptosis = 54%	IC₅₀ = 200 μM IC₅₀ = 50 μM IC₅₀ = 25 μM	[220]
Iridaea cordata Pyropia endiviifolia	Ethyl acetate Hexane extract	–	Human epidermoid carcinoma	A-431	In vitro	Cytotoxicity	–	Inhibitory ratio = 91.1% Inhibitory rate = 56.6%	Conc = 500 μg/ml (24 h)	[221]
Acanthophora spicifera	–	Sulfated polysachharide	Human lung cancer	A549	In vitro	Cytotoxicity and apoptosis	Cytotoxic to A549 cells by swelling, crooking of membrane and chromatin condensation	–	IC₅₀ = 400 μg/ml (48 h)	[222]
Asparagopsis armata Sphaerococcus coronopifolius Asparagopsis armata Sphaerococcus coronopifolius	Dichloromethane extract Methanol extract	Polysaccharide	Human colorectal cancer	Caco-2	In vitro	Antiproliferative and cytotoxicity	–	Loss of cell viability = 98.96% Anti-proliferative = 100% Loss of cell viability = 98.08% Anti-proliferative = 99.04% Loss of cell viability = 92.68% Loss of cell viability = 96.47%	Conc. = 1 mg/ml (24 h) for all Cytotoxicity: IC₅₀ = 21.3 μg/ml Anti-proliferation: IC₅₀ = 36.5 μg/ml	[223]
Gracilaria fisheri	Sulfated galactans	Polysaccharide	Cholangiocarcinoma	HuCCA-1 RMCCA-1	In vitro	Anti-migration	Decrease MMP-9, expression of p-FAK, blocks phosphorylation of EGFR, ERK, increases expression of E-cadherin, and inhibits MAPK/ERK signal transduction pathway	Distance of wound closure = 40.6% Distance of wound closure = 21.1% (24 h) (100 μg/ml)	IC₅₀ = 7 μg/ml Conc = 100 μg/ml (24 h) IC₅₀ = 8 μg/ml Conc = 100 μg/ml (24 h)	[224]
Pterocladiella capillacea	Mertensene	Hlaogenated monoterpene	Human colon adenocarcinoma	HT-29 LS174	In vitro	Apoptosis, and cell cycle arrest	Inhibition of cell viability and induction of caspase-dependent apoptotic pathway via activation of MAPK ERK-1/-2, AKT, and NF-κB pathways. Moreover, mertensene is 2.4 to 3.7 fold toxic against LS174 and arrest G2/M phase in HT-29	Apoptotic cells = 20% Apoptotic cells = 38% Apoptotic cells = 46.7%	Conc. = 50 μg/ml (72 h) Conc. = 70 μg/ml (72 h) Conc. = 90 μg/ml (72 h) Cell viability: IC₅₀ = 56.50 μg/ml IC₅₀ = 49.77 μg/ml	[225]
–	λ-carrageenan	Sulfated polysaccharide	Human mammary carcinoma	MCF-7	In vitro	Anti-angiogenesis	Inhibition of the degradation of heparin sulfate present in extracellular matrix by heparanase to prevent pseudo-vessel formation	Slowing pseudo-vessel formation = 32% (FBS-free medium) Slowing pseudo-vessel formation = 48% (heparanase-rich medium)	Conc. = 200 μg/ml	[226]
Gracilariopsis lemaneiformis	–	Polysaccharide	Human lung cancer Human gastric cancer Mouse melanoma	A549 MKN28 B16	In vitro	Anti-proliferative and apoptosis	Upregulation of Fas/FasL-mediated apoptotic pathway	At 72 h: Cell proliferation inhibition = 41.376% Cell proliferation inhibition = 47.134% Cell proliferation inhibition = 52.151%	Anti-proliferative: IC₅₀ = 50 μg/ml (48 h) IC₅₀ = 78 μg/ml (48 h) IC₅₀ = 90 μg/ml (48 h) Apoptotic: Conc = 60 μg/ml	[227]
Kappaphycus alvarezii	Native carrageenan	Sulfated polysaccharide	Breast carcinoma Colon carcinoma Liver carcinoma Osteosarcoma	MCF-7 HT-29 Hep-G2 MG63	In vitro	Cell viability and growth inhibition	Induction of apoptosis via both mitochondrial- and death receptor-mediated pathways	Reduction in cell viability = 43.63% (150 μg/ml) Growth inhibition = 56.37% (150 μg/ml) Growth inhibition = 67.67% (150 μg/ml) Growth inhibition = 64.81% (150 μg/ml) Growth inhibition = 65.70% (150 μg/ml)	IC₅₀ = 103.2 μg/ml IC₅₀ = 73.87 μg/ml IC₅₀ = 56.71 μg/ml IC₅₀ = 47.85 μg/ml	[228]
Palisada perforata (formerly known as Laurencia papillosa)	–	Sulfated polysaccharide	Breast cancer	MDA-MB-231	In vitro	Apoptosis and cell cycle arrest	Induction of cell death, G₁-phase cell cycle arrest, Bax gene and ROS production, and downregulation of Bcl-2 gene to induce apoptosis	At 24 h: Cell death induction = 52% G₁ phase = 73% Apoptotic cells = 50%	Conc. = 50 μg/ml Conc. = 10 μg/ml Conc. = 50 μg/ml	[229]
Asparagopsis armata Sphaerococcus coronopifolius Asparagopsis armata Sphaerococcus coronopifolius	Dichloromethane extract Methanolic extract	Polysaccharide	Human hepatocellular carcinoma	HepG2	In vitro	Antiproliferative and cytotoxicity	–	Cell viability = 11.22% Anti-proliferation = 98.56% Cell viability = 12.84% Anti-proliferation = 99.61% Cell viability = 1.51% Cell viability = 14.04%	Conc. = 1000 μg/ml (24 h) Cytotoxicity: IC₅₀ = 14.1 μg/ml Anti-proliferation: IC₅₀ = 32.3 μg/ml	[230]
Laurencia obtusa	Methanolic extract	–	Breast cancer	MCF-7	In vitro	Apoptosis	–	Inhibition of cell viability = 82.86%	IC₅₀ = 99.1 μg/ml	[231]
Brown seaweed
Sargassum pallidum	–	Sulfated polysaccharide fractions: SPP-1 and SPP-0.7	Human lung cancer Human hepatoma Murine melanoma	A549 HepG2 B16	In vitro	Anti-proliferative and apoptosis	Increase in the activity of lymphocytes, macrophages, and serum cytokines such as IL-6, IL-1β, iNOS, TNF-α. Expression of genes related to TGF-β signaling, RIG-I-like receptor signaling, p53 signaling, and hippo signaling mediates anti-tumor activity	Inhibitory rate = 64.28% (SPP-0.7) Apoptotic rate = 7.99% Apoptotic rate = 8.01% Apoptotic rate = 3.62% Inhibitory rate = 39.26% (SPP-1) Inhibitory rate = 30.06% (SPP-0.7)	Conc. = 100 μg/ml Conc. = 25 μg/ml Conc. = 100 μg/ml Conc. = 400 μg/ml Conc. = 400 μg/ml Conc. = 25 μg/ml	[232]
Sargassum polycystum	Fucoidan (low molecular weight fraction)	Sulfated polysaccharide	Human leukemia Human breast cancer	HL-60 MCF-7	In vitro	Apoptosis	Mitochondria-mediated apoptotic pathway, G₁ phase cell cycle arrest	–	IC₅₀ = 84.63 μg/ml IC₅₀ = 93.62 μg/ml	[233]
Hizikia fusiforme	Fucose	Sulfated polysaccharide	Human bladder cancer EJ tumor xenografts	MGH-U1 Balb/C nude mice	In vitro In vivo	Anti-proliferative	G₁ phase cell cycle arrest and inhibits MMP-9 expression Decline in the number of cancer cells	–	IC₅₀ = 800 μg/ml Conc. = 20 mg/kg (5 days)	[234]
Sargassum linearifolium Cystoseira crinita	Hot aqueous extract Cold methanolic extract	–	Human breast adenocarcinoma	MCF-7	In vitro	Apoptosis and autophagy	Increased mRNA expression levels of Bax, and Beclin-1 and decreased expression of Bcl-2	–	IC₅₀ = 31.1 μg/ml IC₅₀ = 18.0 μg/ml	[235]
Sargassum hemiphyllum	Oligo-fucoxanthin	–	Human liver cancer	HepG2	In vitro	Apoptosis and cell cycle arrest	Suppression of cell viability, cell cycle arrest in G₁ phase and induction of apoptosis via activation of caspase-8/-9 and regulating the expression of IncRNA profile	Loss of cell viability = 81.34% G₁ phase = 39.5%	Conc. = 50 μg/ml Conc. = 50 μg/ml	[236]
Fucus vesiculosus	Hydrothermal treated fucoidan	Polysaccharide	Burkitt lymphoma	Raji	In vitro	Anti-proliferative	–	Reduced viable cells = 88%	Conc. = 150 μg/ml (72 h)	[237]
Sargassum fusiforme	–	Polysaccharide	Nasopharyngeal carcinoma cell line; CNE cells were injected into axilla of left hind leg	Balb/c nude mice	In vivo	Anti-proliferative	The growth of tumor was inhibited and the tumor weight was reduced through by increasing the serum levels of IL-1β, TNF-α, nitric oxide, and IgM	Tumor weight = 1.61 g Tumor inhibition rate = 17.9% Tumor weight = 1.42 g Tumor inhibition rate = 27.6% Tumor weight = 1.12 g Tumor inhibition rate = 42.9%	Conc. = 50 mg/kg Conc. = 100 mg/kg Conc. = 200 mg/kg	[238]
Sargassum fusiforme	–	Polysaccharide	Human hepatoma HepG2 cells inoculated in mice	HepG2 Balb/c nude mice	In vitro In vivo	Anti-proliferative and apoptosis	Increase in the level of Bax protein and decrease in Bcl-2 protein Tumor growth was inhibited and the weight of the tumor was reduced	Apoptotic cells = 8.1% Apoptotic cells = 16.1% Apoptotic cells = 50.7% Apoptotic cells = 40.1% Apoptotic cells = 43.2% Tumor weight = 1.46 g Tumor weight = 1.25 g Tumor weight = 0.99 g	IC₅₀ = 1158.6 μg/ml Conc. = 125 mg/ml Conc. = 250 mg/ml Conc. = 500 mg/ml Conc. = 1000 mg/ml Conc. = 2000 mg/ml Conc. = 100 mg/kg Conc. = 200 mg/kg Conc. = 400 mg/kg	[239]
Dictyota dichotoma Dictyota spiralis	Cold methanolic extract	–	Breast cancer	MCF-7	In vitro	Apoptosis	–	Inhibition of cell viability = 91.32% (50 μg/ml) Inhibition of cell viability = 82.14%	IC₅₀ = 17.2 ng/ml IC₅₀ = 35.9 μg/ml	[231]
Turbinaria conoides	Fucoidan	Sulfated polysaccharide	Human lung adenocarcinoma	A549	In vitro	Anti-proliferative, apoptosis, and cell cycle arrest	Growth-inhibitory activity, and cell cycle arrest in G₀/G₁ phase	Cell number in G₀/G₁ phase = 76.3% (24 h) Cell number in G₀/G₁ phase = 78.86% (48 h) Cell proliferation decreased by 3.5 fold	GI₅₀ = 75 μg/ml Conc. = 5 μM	[240]
–	Fucoxanthin	Sulfated polysaccharide	Human glioma	U87 U251 BALB/c-nude mice injected with U87 cells	In vitro In vivo	Anti-proliferative and apoptosis	Activates apoptosis by inhibiting P13K/Akt/mTOR pathway and suppresses invasion and migration by blocking p38-MMP-2/9 pathway Reduced tumor volume and weight	Apoptotic rate = 14.32 Apoptotic rate = 28.36 Apoptotic rate = 17.00 Apoptoric rate = 27.31 Reduced tumor volume = 1644 mm³	Conc. = 25 μM Conc. = 50 μM Conc. = 25 μM Conc. = 50 μM Conc. = 200 mg/kg/day	[241]
Fucus vesiculosus	Fucoidan	Sulfated polysaccharide	Diffuse large B cell lymphoma	SUDHL-4 OCI-LY8 NU-DUL-1 TMD8 U2932 DB OCI-LY8 Injected NOD/SCID mice	In vitro In vivo	Anti-proliferative, apoptosis and cell cycle arrest in G₀/G₁	Induction of G₀/G₁ cell cycle arrest, caspase-dependent cell apoptosis, p21 upregulation and cyclin D1, Cdk4, Cdk6 downregulation Fucoidan reduced tumor volume and tumor weight in xenograft mouse model	G₀/G₁ cell population = 61.21 (24 h) Tumor weight = 0.5 g	Anti-proliferation: IC₅₀ = 80 μg/ml IC₅₀ = 82.3 μg/ml IC₅₀ = 93.7 μg/ml IC₅₀ = 97.5 μg/ml IC₅₀ = 101.6 μg/ml IC₅₀ = 95.5 μg/ml Conc. = 100 mg/kg/day for 21 days	[242]
Dictyota cilliolata Dictyota menstrualis	Methanolic extract	–	Human cervical adenocarcinoma	HeLa	In vitro	Cytotoxicity and apoptosis	Induction of mitochondria-dependent apoptotic pathway by activation of caspase-3 and − 9, and cell cycle arrest in S phase in MEDC	Cell viability inhibition rate = 50% Apoptotic cells = 4.32% Cell viability inhibition rate = 80% Apoptotic cells = 14.9%	Conc. = 0.2 mg/ml (72 h) Conc. = 0.2 mg/ml (48 h)	[243]
Ascophyllum nodosum	Ascophyllan	Sulfated polysaccharide	Murine melanoma B16 melanoma cells injected into tail vein	B16 C57BL/6 mice	In vitro In vivo	Anti-adhesive anti-migratory Anti-metastatic	Inhibition of cell adhesion and invasion by reducing the level of N-cadherin, MMP-9 and enhancing the level of E-cadherin Decline in the number of metastatic nodules on the lung surface	Cell adhesion inhibitory activity = 47% Cell adhesion inhibitory activity = 62% Cell adhesion inhibitory activity = 69% Invasion inhibition = 57% Invasion inhibition = 67% Invasion inhibition = 78% Anti-proliferative	Cell adhesion inhibition: Conc. = 10 μg/ml Conc. = 100 μg/ml Conc. = 1000 μg/ml Invasion inhibition: Conc. = 5 μg/ml Conc. = 10 μg/ml Conc. = 20 μg/ml Conc. = 25 mg/kg/day	[244]

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