Table 1.

Anticancer effects and mechanisms of action of various secondary metabolites of marine cyanobacteria.

Class	Secondary Metabolite	Biological Source	Cell Lines Used	Effects and Mechanisms	IC50 Values	References
Anthracycline	Komodoquinone A(1)	Streptomyces sp. KS3	Neuro 2A neuroblastoma cell	Neuritogenic activity, ↑cell differentiation	1 μg/mL	[84]
Phenoxazin-3-one	Chandrananimycins A, B, C (2,3,4)	Actinomadura sp.	CCL HT29 (colon cancer); MEXF 514L (melanoma); LXFA 526L, LXFL 529L (lung cancer); CNCL SF268, LCL H460, MACL MCF-7 (breast cancer); PRCL PC3M, RXF 631L (kidney tumor cells)	Anti-tumor activity	~1.4 μg/mL	[85]
Glycosilated polyketide	Ankaraholide A (5)	Geitlerinema sp.	NCI-H460; Neuro-2a; MDAMB- 435 cell lines	┴ Proliferation; ↑cytotoxicity	119; 262; 8.9 nM	[86]
Polyketide	Swinholide A (6)	Symploca cf. sp.	Several cancer cell lines	Antitumor activity; ┴ proliferation; ↑cytotoxicity; disruption of the actin cytoskeleton	0.37 nM–1.0 μM	[86]
Pentapeptide	Symplostatin 1 (7)	Symploca hydnoides	MDA-MB-435 (breast cancer cell), SK-OV-3 (ovarian cancer cell), NCI/ADR (multidrug-resistance ovarian cancer cell), A-10 (smooth muscle cells), and HUVEC (Human umbilical vein endothelial cells); in vivo study (murine colon 38 and murine mammary 16/C carcinoma cells)	Antitumor activity; ↑phosphorylation of Bcl-2; ↑micronuclei formation, ↑caspase 3, ↑apoptosis, cell cycle arrest at G2/M Phase, ┴tubulin accumulation	0.15 ± 0.03 nM; 0.09 ± 0.02 nM; 2.90 ± 0.64 nM; 1.8 ± 0.43 nM; 0.16 ± 0.02 nM	[72,87]
Macrocyclic depsipeptide	Grassypeptolide, Grassypeptolide A, B and C (8, 9, 10)	Lyngbya confervoides	human osteosarcoma (U2OS), cervical carcinoma (HeLa), colorectal adenocarcinoma (HT29), and neuroblastoma (IMR-32);	Anticancer activity; ┴proliferation; Cell cycle arrest at G1 or G2/M Phase	1–4.2 μM for grassypeptolide in all cell lines. Grassypeptolide A: 1.22 &1.01 μM in HT29 and Hela. Grassypeptolide B: 4.07 and 2.93 μM in HT29 and Hela. Grassypeptolide C: 76.7 and 44.6 nM HT29 and Hela.	[88,89]
ketopeptide	Curacin A (11)	Lyngbya majuscule	Non-small cell lung cancer cell line (A549)	Anticancer activity; ┴proliferation; ↑apoptosis; cell cycle arrest at G2/M Phase; binds to tubulin at colchicines binding site	0.72 ± 0.02 μM	[90,91,92,93,94,95]
Linear peptide	Tasiamide B (12)	Symploca sp.	ĸB oral epidermoid cancer; human colon carcinoma (LoVo) cells	┴Proliferation; ↑cytotoxicity	0.48; 3.47 μg/mL	[96]
Cyclic depsipeptide	Apratoxin A (13)	Lyngbya majuscula	U2OS osteosarcoma; HeLa cervical carcinoma; in LoVo colon carcinoma; ĸB carcinoma cancer cells	┴Secretory pathway; ┴cell cycle at G1 Phase; ↑cytotoxicity; ┴translocation of protein targeting Sec61α	50; 2.2; 0.36; 0.52 nM	[97,98]
	Apratoxin B (14)	Lyngbya sp.	ĸB oral epidermoid cancer and LoVo colon cancer lines	↑Cytotoxicity	21.3; 10.8 nM	[97]
	Apratoxin C (15)	Symploca cf. sp.	Several cancer cell lines	↑Cytotoxicity	1.0; 0.73 nM	[97]
	Apratoxin D (16)	Lyngbya majuscule; Lyngbya sordida	H-460 lung cancer		2.6 nM	[98]
	Apratoxin E (17)	Lyngbya bouilloni	U2OS osteosarcoma, HT29 colon adenocarcinoma and HeLa epithelial carcinoma	↑Antiproliferative Activity	59; 21; 72 nM	[99]
	Apratoxin F (18)	Lyngbya sp.	H-460 lung cancer; HCT-116 colorectal cancer cells	↑Cytotoxicity	2; 36.7 nM	[100]
	Apratoxin G (19)				14 nM; Not specified
	Aurilide B (20)	Lyngbya majuscula	NCI-H460 human lung tumor and neuro-2a mouse neuroblastoma cells	↑Antiproliferative activity; ↑OPA1 synthesis, ↑apoptosis	0.04; 0.01 µM	[101,102]
	Aurilide C (21)	Lyngbya majuscula	U2OS osteosarcoma, HT29 colon adenocarcinoma and HeLa epithelial carcinoma		0.13; 0.05 µM
	Coibamide A (22)	Leptolyngbya sp.	MDA-MB-231, melanoma LOX IMVI, leukemia HL-60 and astrocytoma SNB75	↑Cytotoxicity; ┴cell cycle at G1 Phase	2.8; 7.4; 7.4 and 7.6 nM	[103]
			glioblastoma cell lines U87-MG and SF-295	↑Cytotoxicity	20 nM	[104]
			Normal human umbilical vein endothelial cells (HUVECs)	┴Proliferation; ↓VEGFR2	0.3–3 nM
			Human U87-MG glioblastoma cells and SF-295 glioblastoma cells	↑Cytotoxicity; ↑autophagy	28.8, 96.2 nM	[105]
	Hoiamide A (23)	Lyngbya majuscule, Phormidium gracile	H-460 lung cancer and neuro-2a mouse neuroblastoma	↑Cytotoxicity; ↑neurotoxicity	11.2; 2.1 μM	[106]
	Hoiamide B (24)				8.3 μM; no effect on neuro-2a
	Homodolastatin 16 (25)	Lyngbya majuscule	WHCO1 and WHCO6 esophageal cancer; ME180 cervical cancer	↑Apoptosis; ┴cell cycle at G2/M Phase; ↑cytotoxicity	4.3 and 10.1; 8.3 µg/mL	[107]
	Largazole (26)	Symploca sp.	MDA-MB-23I breast cancer; U2OS osteosarcoma; colon HT29; neuroblastoma IMR-32; nontransformed murine mammary epithelial cells NMuMG; HCT-116 colorectal carcinoma	↑Cytotoxicity; ┴tumor; cell cycle arrest at G2/M Phase; ┴HDAC	7.7; 55; 12; 16; 122 nM; Not specified	[108,109]
	Lyngbyabellin A (27)	Lyngbya majuscula	ĸB nasopharyngeal carcinoma and LoVo colon adenocarcinoma	↑Cytotoxicity; ┴tumor; cell cycle arrest at G2/M Phase; ↑actin polymerization	0.03; 0.05 μg/mL	[110]
	Lyngbyabellin B (28)	Lyngbya majuscula			0.10; 0.83 μg/mL	[110]
	Lyngbyabellin E (29)	Lyngbya majuscula Symploca sp.	NCI-H460 human lung tumor and neuro-2a mouse neuroblastoma cells	┴Tumor growth; ┴cell microfibrils network	0.4; 1.2 μM	[111]
	Lyngbyabellin F (30)	Lyngbya majuscula		↑Cytotoxicity	1; 1.8 μM
	Lyngbyabellin G (31)	Lyngbya majuscula			2.2; 4.8 μM	[111]
	Lyngbyabellin H (32)				0.2; 1.4 μM	[111]
	Lyngbyabellin I (33)	Lyngbya majuscula			1; 0.7 μM	[111]
	Lyngbyabellin N (34)	Moorea bouillonii	HCT116 (colon cancer cell line)	Anticancer activity; ↑cytotoxicity	40.9 ± 3.3 nM	[112]
	Majusculamide C (35)	Lyngbya majuscule	Ovarian carcinoma OVCAR-3, kidney cancer A498, lung cancer NCI-H460, colorectal cancer KM20L2; glioblastoma SF-295	Anticancer activity; ↑cytotoxicity	0.51; 0.058; 0.0032; 0.0013; 0.013 μg/mL	[110,113]
	Desmethoxymajusculamide C (36)	Lyngbya majuscule	HCT-116 human colon carcinoma cells	Selective antitumor activity	20 nM	[110]
	Obyanamide (37)	Lyngbya confervoides	ĸB and LoVo cells	Anticancer activity	0.58; 3.14 µg/mL	[114]
	Palau’amide (38)	Lyngbya confervoides	ĸB oral epidermoid cancer cells	Anticancer activity	13 nM	[115]
	Palmyramide A (39)	Lyngbya majuscule	Neuro2a cells and human lung cell H-460	Anticancer activity; ↑cytotoxicity; blocking the voltage regulated sodium channel	17.2; 39.7 µM	[116]
	Pitipeptolide A (40)	Lyngbya majuscule	HT29 colon adenocarcinoma cancer cells, MCF-7 and LoVo colon cancer	Anticancer activity; ↑cytotoxicity	13; 13 µM & 2.25 µg/mL	[117,118]
	Pitipeptolide B(41)	Lyngbya majuscula	HT29 colon adenocarcinoma cancer cells, MCF-7 and LoVo colon cancer	Anticancer activity; ↑cytotoxicity	13; 11 µM; 1.95 µg/mL	[117,118]
	Pitiprolamide (42)	Lyngbya majuscula	HCT116 colorectal carcinoma and MCF7 breast adenocarcinoma	Anticancer activity, ↑cytotoxicity	33; 33 µM	[119]
	Tasipeptins A (43)	Symploca sp.	ĸB oral epidermoid cancer	Anticancer activity, ↑cytotoxicity	0.93 µM	[120]
	Tasipeptins B (44)	Symploca sp.	ĸB oral epidermoid	Anticancer activity, ↑cytotoxicity	0.82 µM	[120]
	Ulongapeptin (45)	Lyngbya sp.	ĸB oral epidermoid cancer	Anticancer activity; ↑cytotoxicity	0.63 µM	[121]
	Veraguamide A-G (46–52)	Symploca cf. hydnoides, Oscillatoria margaritifera	HT29 colon adenocarcinoma; HeLa cervical carcinoma	Anticancer activity; ↑cytotoxicity	26; 2 µM & 141 nM; 30 & 17 µM; 5.8 & 6.1 µM; 0.84 & 0.54 µM; 1.5 & 0.83 µM; 49 & 49 µM; 2.7 & 2.3 µM	[122,123]
	Wewakpeptins A-D (53–56)	Lyngbya semiplena	H-460 lung cancer	Anticancer activity; ↑cytotoxicity	0.4 µM	[124]
Cyclic heptapeptides	Nostocyclopeptide A1 & A2 (57, 58)	Nostoc sp.	ĸB oral epidermoid cancer and LoVo colon carcinoma cell line	Anticancer activity; ↑cytotoxicity	1 & 1 µM for both	[125]
Cyclopeptide	Symplocamide (59)	Symploca sp.	Non-small cell lung cancer cells H-460 and neuro-2a neuroblastoma cells	Anticancer activity; ↑cytotoxicity	40; 29 nM	[110]
Cyclicpeptide	Tasiamide (60)	Symploca sp.	Human nasopharyngeal carcinoma (ĸB) and human colon carcinoma (LoVo) cells	Anticancer activity; ↑cytotoxicity	0.48; 3.47 µg/mL	[126]
Linear tetrapeptide	Belamide A (61)	Symploca sp.	MCF7 breast cancer cell; HCT-116 colon cancer cell	Anticancer activity; ↑cytotoxicity; depolymerizing effect on microtubule in A-10 cells; antimitotic activity	1.6 µM; 0.74 µM	[127]
Peptide	Bisebromoamide (62)	Lyngbya sp.	HeLa S3 cells; a panel of 39 human cancer cell lines of the Japanese Foundation for Cancer Research (JFCR39) Cancer Research	↑Cytotoxicity; ┴protein kinases; ┴phosphorylation of ERK	0.04 µg/mL; average 40 nM	[128,129]
Lipopeptides	Dragonamide, Pseudodysidenin (63, 64)	Lyngbya majuscula	P-388; A-549 lung epithelial adenocarcinoma, HT-29 colon adenocarcinoma; MEL-28 melanoma	Anticancer activity; ↑cytotoxicity	> 1 µg/mL	[130]
Lipopeptide	Kalkitoxin (65)	Phormidium sp.	HCT-116 colon cancer cell; T47D breast tumor cells	Anticancer activity; ↑cytotoxicity; ┴hypoxia-induced activation of HIF-1; ↓mitochondrial oxygen consumption at electron transport chain (ETC) complex I (NADH-ubiquinone oxidoreductase); blocking of VEGF	2.7 nM; 5.6 nM	[131]
Lipopeptide	Somocystinamide A (66)	Lyngbya majuscula	Jurkat, CEM (leukemia), A549 (lung carcinoma), Molt4 (T cell leukemia), M21 melanoma, and U266 myeloma cell lines	↑Cytotoxicity; ↑apoptosis via caspase 8	3; 14; 46; 60 nM; 1.3; 5.8 µM	[132]
Lipopeptide, Lyngbic acid derivative	Malyngamide 2 (67)	Lyngbya sordida	H-460 lung cancer	↑Cytotoxicity	27.3 µM	[133]
	Malyngamide C, J, & K (68, 69, 70)	Lyngbya majuscula	NCI-H460, Neuro-2a, and HCT-116	↑Cytotoxicity	1.4; 3.1; 0.2 µg/mL 10.8, 4 µg/mL, nd 1.1; 0.49 µg/mL, nd	[134]
Peptide ester	Malevamide D (71)	Symploca hydnoides Kü tzing ex Gomont	P388, Lung cancer A-549, colon cancer HT-29 Melanoma MEL-28	↑Cytotoxicity	0.3–0.7 nM 0.7 nM	[135]
Cyclodepside	Malyngolide dimer (72)	Lyngbya majuscule	NCI H-460 human lung tumor cell line	Moderate cytotoxicity; anticancer activity	Not specified	[136]
Macrolide depsipeptide	Cryptophycin 1 (73)	Nostoc sp.	L1210 murine leukemia cells	Anticancer activity; ↑disruption of microtubule assembly	Not specified	[137,138]
			kB cells and LoVo cell	↑Apoptosis	4.58, 7.63 pM	[139]
			MDA-MB-435 mammary adenocarcinoma; SKOV3 ovarian carcinoma cell lines	┴Proliferation; ┴cell cycle at G2/M Phase	50 pM	[140,141]
Cyclic depsipeptide	Lagunamides A, B (75, 76)	Lyngbya majuscule	P388 (a murine leukemia cell line)	↑Cytotoxicity	6.4 and 20.5 nM	[142]
	Lagunamides C (77)		P388, A549, PC3, HCT8, and SK-OV3carcinoma cell lines		2.1 to 24.4 nM	[143]
Macrolide glycoside	Biselyngbyaside (78)	Lyngbya sp.	HeLa S3 epithelial carcinoma; SNB-78 central nervous system cancer; NCI H522 lung cancer	┴Proliferation of cancer cell; induced cytotoxicity	0.1 µg/mL; 0.036; 0.067 µM	[144]
	Biselyngbyasid B (79)	Symploca hydnoides	HeLa S3 cells and HL60 cells	┴Proliferation of cancer cell; induced cytotoxicity	3.5 & 0.82 µM	[145]
	Biselyngbyasid E & F (80, 81)	Lyngbya sp.	HeLa and HL60 cells	┴Proliferation of cancer cell; induced cytotoxicity	0.19 & 0.071 µM; 3.1 & 0.66 µM	[146]
Glycomacrolide	Lyngbyaloside B (82)	Lyngbya sp.	ĸB nasopharyngeal carcinoma and LoVo colon adenocarcinoma	↑Cytotoxicity; anticancer activity	4.3; 15 µM	[147]
	2-epi-lyngbyalosid (83)	Lyngbya bouillonii	HT29 colorectal adenocarcinoma and HeLa cells	Anticancer activity; ┴proliferation	38 and 33 µM	[148]
	18E-lyngbyaloside C; 18Z-lyngbyaloside C (84, 85)	Lyngbya sp.	HT29 colorectal adenocarcinoma and HeLa cells	Anticancer activity; ┴proliferation;	13 & 9.3 µM; >100 µM & 53 µM	[148]
Macrolide	Biselyngbyolide A; Biselyngbyolide B (86, 87)	Lyngbya sp.	HeLa S3 cells and HL60 cells	Anticancer activity	0.22 & 0.027 µM; 0.028 & 0.0027 µM	[149]
Macrolide	Koshikalide; Acutiphycin and 20, 21-didehydroacutiphycin (88, 89, 90)	Lyngbya sp., Oscillatoria acutissima	HeLa S3 cells; KB and NIH/3T3 cells	Anticancer activity; ↑cytotoxicity	42 µg/mL, Not specified for Acutiphycin and 20, 21-didehydroacutiphycin	[150,151]
Glycosylated macrolide	Lyngbouilloside (91)	Lyngbya bouillonii	Neuro-2a neuroblastoma cells	Anticancer activity; ↑cytotoxicity	17 µM	[152]
Glycosylated macrolide	Polycavernoside D (92)	Okeania sp.	H-460 human lung cancer cell line	┴Proliferation	EC50 = 2.5 µM	[153]
Macrocyclic lactone	Tolytoxin(93) 6-hydroxyscytophycin B (95), 19-O-demethylscytophycin C (96), and 6-hydroxy-7-O-methylscytophycin E (98)	Seytonema ocellaturn Lyngbye ex Bornet and Flahault	L1210 (murine leukemia), LoVo, kB, HEp-2 (human epithelial type 2 cells), HL-60 (Human promyelocytic leukemia), HBL-100 (breast cancer cell), T47-D (human ductal carcinoma), COLO-201 (colon adenocarcinom), KATO-III (human gastric carcinoma) Nasopharynx cell (ĸB cells), &LoVo cells	Anticancer activity; ↑cytotoxicity;	3.9, 8.4, 5.3, 2.3, 4.8, 2.4, 4.9, 0.52, and 0.78 nM >5 ng/mL	[154,155]
Macrolactone	Caylobolide A (99), Caylobolide B (100)	Lyngbya majuscula Phormidium sp.	HCT-116 colon tumor HT29 colorectal adenocarcinoma, and HeLa cervical carcinoma	Anticancer activity; ↑cytotoxicity	9.9 µM (same for both caylobolide A & B) 4.5; 12.2 µM	[156,157]
Fatty acid amines	Isomalyngamide A (101), and Isomalyngamide A-1 (102)	Lyngbya majuscula	Breast cancer MCF-7 and MDA-MB-231	┴Proliferation; ┴apoptosis; ┴cell migration; antimetastatic activity	4.6 & 2.8 µM; 12.7 µM & > 20 µM	[158]
	Jamaicamides A, B, & C (103, 104, 105)	Lyngbya majuscula	H-460 lung cancer and Neuro-2a mouse neuro blastoma cell lines	┴proliferation	LC50: 15 µM for all	[159]
Pigment	Scytonemin (106)	Stigonema sp.	Jurkat T cells	↑Apoptosis; ┴formation of mitotic spindle; ┴protein serine/threonine kinase activity	7.8 μM	[160,161]
Boron containing metabolite	Borophycin (107)	Nostoc spongiaeforme, N. linckia	Human cancer cell lines ĸB colorectal adenocarcinoma and LoVo (human epidermoid carcinoma)	┴Cancer; ┴cell cycle at G2/M Phase	Not specified	[48,162]
Phenanthridine alkaloids	Calothrixins A and B (108, 109)	Calothrix sp.	Human carcinoma cell line (HeLa)	↑Cytotoxicity;┴proliferation	40and 350 nM	[163,164]
			CEM leukemia cells	┴Proliferation;┴cell cycle at G1 and G2/M Phases	0.20 to 5.13 µM	[165]

Various symbols (↑, ↓ and ┴) indicate increase, decrease and inhibition in the obtained variables, respectively.