Table 1.
List of marine-derived anticancer peptides and their mode of action.
| Name of Peptide | Natural Sources | Class/Types | Mode of Action/Investigative Status | Growth Inhibition Concentration (Cell Line) | Ref. |
|---|---|---|---|---|---|
| Apratoxin A–D (1–4) |
Cyanobacteria: Lyngbya majuscula, L. sordida | Cyclic depsipeptide |
Induction of G1 phase cell cycle arrest and apoptosis/in vitro only | IC50: 0.36 nM (LoVo), 0.52 nM (KB), 2.6 nM (H-460) |
[29,30,31,32,33,34,35] |
| Aurilide (5), B (6), C (7) | Cyanobacteria: Lyngbya majuscula | Cyclic depsipeptide |
Cytotoxicity /in vitro only |
LC50: 40–130 nM (NCI-H460), 10–50 nM (neuro-2a), GI50 < 10 nM (NCI 60 cell line panel) |
[36,37] |
| Bisebromoamide (8) | Cyanobacteria: Lyngbya majuscula | Linear peptide | Activation of ERK pathway/in vitro only | IC50: 0.04 μg/mL (HeLa S3), GI50 = 40 nM (JFCR39 cell line panel) |
[38] |
| Coibamide A (9) | Cyanobacteria: Leptolyngbya sp. | Cyclic depsipeptide |
Cancer cell proliferation inhibition/in vitro only | LC50 < 23 nM (NCI-H460, neuro-2a) GI50 < 7.6 nM (NCI 60 cell line panel) |
[39] |
| Cryptophycin (10) | Cyanobacteria: Nostoc sp. | Depsipeptide | Apoptosis and microtubule inhibition /in vitro only (Cryptophycin-52: Phase II human clinical trial) |
IC50 < 50 pM (MDR tumor cell lines), | [40,41,42,43,44] |
| Desmethoxymajusculamide C (11) | Cyanobacteria: Lyngbya majuscula | Cyclic depsipeptide |
Tubulin polymerization Inhibition/in vitro only |
IC50: 20 nM (HCT-116), | [45] |
| Grassypeptolide A–E (12–16) | Cyanobacteria: Lyngbya confervoides | Cyclic depsipeptide |
Induction of G2/M phase cell cycle arrest /in vitro only |
IC50: 192–335 nM (HeLa), 407–599 nM (neuro-2a) | [46,47] |
| Hantupeptin A (17) | Cyanobacteria: Lyngbya majuscula | Cyclic depsipeptide |
Cytotoxicity /in vitro only |
IC50: 32 nM (MOLT-4), 4 μM (MCF-7) | [48,49,50] |
| Hectochlorin (18) | Cyanobacteria: Lyngbya majuscula | Lipopeptide | Hyperpolymerization /in vitro only |
IC50: 20 nM (CA46), 300 nM (PtK2) | [51] |
| Hormothamnin A (19) | Cyanobacteria: Hormothamnion enteromorphoides | Cyclic undecapeptide | Cytotoxicity /in vitro only |
IC50: 0.13–0.72 μg/mL (SW1271, A529, B16-F10, HCT-116)) | [52] |
| Itralamide A (20), B (21) | Cyanobacteria: Lyngbya majuscula | Cyclic depsipeptide |
Antiproliferative activity/in vitro only | IC50: 6 μM (HEK293) | [53] |
| Lagunamide A–C (22–24) | Cyanobacteria: Lyngbya majuscula | Cyclic depsipeptide |
Antiproliferative activities and apoptosis/in vitro only | IC50: 6.4–24.4 nM (P388) | [54,55] |
| Largazole (25) | Cyanobacteria: Symploca sp. | Cyclic depsipeptide |
Stimulation of histone hyperacetylation in the tumor/in vitro only | GI50: 7.7 nM (MDA-MB-231), 122 nM (NMuMG), 55 nM (U2OS), 480 nM (NIH3T3) | [56,57,58,59,60] |
| Laxaphycin A (26), B (27) | Cyanobacteria: Lyngbya majuscula | Cyclic peptide | Antiproliferative activities/in vitro only |
IC50 < 2 μM (CEM-WT) | [61,62,63] |
| Lyngbyabellin A (28), E (29), B (30) | Cyanobacteria: Lyngbya majuscula | Lipopeptides | Cytoskeletal actin disruption/in vitro only | IC50: 0.03–0.1 μg/mL (KB), IC50: 0.5–0.83 μg/mL (LoVo), LC50: 0.4–1.2 μg/mL (NCI-H460, neuro-2a) |
[64,65] |
| Lyngbyastatin 4–7 (31–34) | Cyanobacteria: Lyngbya sp. | Depsipeptide | Porcine pancreatic elastase inhibition /in vitro only |
IC50: 120–210 μM (elastase inhibition) | [66,67] |
| Symplocamide A (35) | Cyanobacteria: Symploca sp. | Cyclic depsipeptide | Proteasome inhibition/in vitro only | IC50: 40 nM (NCI-H460), 29 nM (neuro-2a) | [68] |
| Tasiamide (36), B (37) | Cyanobacteria: Symploca sp. | Linear peptide | Cytotoxicity /in vitro only |
IC50: 0.48 μg/mL (KB), 3.47 μg/mL (LoVo) | [69,70,71] |
| Veraguamide A (38), D (39), E (40) | Cyanobacteria: Oscillatoria margaritifera, Symploca cf. Hydnoides sp. | Cyclic depsipeptide | Cytotoxicity /in vitro only |
LC50: 141 nM (H-460), IC50: 0.5–1.5 μM (HT29, HeLa) | [72,73] |
| Azonazine (41) | Fungus: Aspergillus insulicola | Hexacyclic dipeptide | Cytotoxicity /in vitro only |
IC50 < 15 ng/mL (HCT-116) | [74] |
| Sansalvamide A (42) | Fungus: the genus Fusarium | Cyclic depsipeptide |
Apoptosis and inhibition of topoisomerase I /in vitro only |
IC50: 4.5 μg/mL (HT29) | [75,76] |
| Scopularides A (43), B (44) | Fungus: Scopulariopsis brevicaulis | Cyclic depsipeptide |
Cytotoxicity /in vitro only |
IC50: 10 μg/mL (Colo357, Panc89, HT29) | [77] |
| Arenastatin A (45) | Sponge: Dysidea arenaria | Cyclic depsipeptide |
Inhibition of microtubule assembly /in vitro only |
IC50: 5 pg/mL (KB) | [78,79,80,81,82,83] |
| Discodermin A–H (46–53) | Sponge: Discodermia kiiensis | Tetra- decapeptide |
Membrane permeabilization /in vitro only |
IC50: 0.02–20 μg/mL (P388, A549) | [84] |
| Geodiamolide H (54) | Sponge: Geodia corticostylifera | Cyclic depsipeptide |
Antiproliferative activity /in vitro only |
G100: 18.6 nM (OV Car-4), | [85,86,87] |
| Hemiasterlin (55), A (56), C (57) | Sponge: Auletta sp., Siphonochalina sp. | Linear tripeptide |
Inhibition of tubulin polymerization /Phase I human clinical trial, (HT1286: Phase I) |
IC50: 0.0484–0.269 nM (PC3), 0.404–10.3 nM (NFF), | [88,89,90,91,92,93,94,95] |
| Homophymine A–E (58–62), A1–E1 (63–67) | Sponge: Homophymia sp. |
Cyclic depsipeptide |
Activation of caspase-3 and 7/in vitro only | IC50: 2–100 nM (MCF7/MCF7R, HCT116/HCT15, HL60/HL60R) | [96] |
| Jaspamide (68) | Sponge: Jaspis johnstoni | Cyclic depsipeptide |
Activation of caspase-3, depression of Bcl-2 protein expression /in vitro only |
IC50 : 0.04 ng/mL (P388) | [97,98,99] |
| Koshikamide B (69), F–H (70–72) | Sponge: Theonella sp. | Peptide lactone | Cytotoxicity /in vitro only |
IC50: 0.45–2.3 μM (P388), 5.5–10 μM (HCT-116) | [100,101] |
| Microcionamide A (73), B (74) | Sponge: Clathria (Thalysias) abietina | Cyclic heptapeptide |
Cytotoxicity /in vitro only |
IC50: 125–177 nM (MCF-7), 98–172 μM (SKBR-3) | [102] |
| Orbiculamide A (75) | Sponge: Theonella sp. | Cyclic peptide | Cytotoxicity /in vitro only |
IC50: 4.7 μg/mL (P388) | [103] |
| Papuamide A–F (76–81) | Sponge: Theonella mirabilis, T. swinhoei | Cyclic depsipeptide | Cytotoxicity and inhibition of infection /in vitro only |
IC50: 0.75 ng/mL (human cell line panel) | [83,104,105] |
| Phakellistatin 1 (82), 13 (83) | Sponge: Phakellia carteri | Cyclic heptapeptides | Antiproliferative activity/in vitro only |
ED50: 7.5 ug/mL (P388), IC50: 0.75 ng/mL (BEL-7404) | [106,107,108] |
| Rolloamide A (84) | Sponge: Eurypon laughlini | Cyclic heptapeptides | Tubulin polymerization inhibition/in vitro only |
IC50: 0.4–5.8 μM (SKBR3, A2780) | [109] |
| Scleritodermin A (85) | Sponge: Scleritoderm nodosum | Cyclic peptide | Microtubule assembly inhibition/in vitro only |
IC50 < 2 μM (HCT116, SKBR3, A2780) | [110,111] |
| Aplidin (plitidepsin, 86) |
Tunicate: Aplidium albicans | Cyclic depsipeptide |
Activation of JNK and p38 MAPK/Phase III human clinical trial | IC50: 0.2–27 nM (CFU-GEMM, CFU-GM, BFU-E) | [112,113,114,115,116,117,118,119,120,121] |
| Didemnin B (87) | Tunicate: Trididemnum solidum | Cyclic depsipeptide |
Apoptosis/Phase II human clinical trial |
IC50: 2 ng/mL (L1210) | [122,123,124] |
| Cycloxazoline (88) | Ascidia: Lissoclinum bistratum |
Cyclic hexapeptide |
Apoptosis/in vitro only | IC50: 0.5 μg/mL (MRC5CV1, T24) | [125] |
| Diazonamide A (89) | Ascidia: Diazona angulata | Macrocyclic peptide |
Tubulin polymerization inhibition/in vitro only |
IC50: 2–5 nM (CA46, MCF7, PC3, A549) | [126,127] |
| Mollamide B (90), C (91) | Ascidia: Didemnum molle | Cyclic depsipeptide | Antiproliferative activity/in vitro only |
IC50: 1 μg/mL (P388), 1 μg/mL (A549, HT29) | [128,129,130] |
| Tamandarin A (92), B (93) | Ascidia: Didemnum sp. | Cyclic depsipeptide |
Cytotoxicity /in vitro only |
IC50: 1.79 μg/mL (BX-PC3), 1.36 μg/mL (DU145), 0.99 μg/mL (UMSCC10b) | [131] |
| Trunkamide A (94) | Ascidia: Lissoclinum sp. |
Cyclic peptide | Cytotoxicity /in vitro only |
IC50: 0.5 μg/mL (P388, A549, HT29), 1.0 μg/mL (MEL-28) | [132] |
| Virenamides A–C (95–97) | Ascidia: Diplosoma virens |
Linear tripeptides | Apoptosis /in vitro only |
IC50: 5–10 μg/mL (P388, A549, HT29, CV1) | [133] |
| Vitilevuamide (98) | Ascidia: Didemnum cuculiferum, Polysyncranton lithostrotum |
Bicyclic depsipeptide | Tubulin polymerization inhibition/in vitro only |
IC50: 6–311 nM (P388, A549, HT29) | [122,134] |
| Dolastatin 10 (99), 15 (100) | Mollusk: Dolabella auricularia | Linear peptide | Microtubule assembly inhibition and Bcl-2 phosphorylation /Human clinical trial Dolastatin 10: phase II (TZT-1027: Phase III) Dolastatin 15: preclinical (ILX651: Phase II, LU-103793: Phase I) |
IC50: 50–5000 pM (CA46), 0.5–3 nM (L1210) | [135,136,137,138,139,140,141] |
| Kahalalide F (101) | Mollusk: Elysia rufescens | Depsipeptide | ErbB3 protein and PI3K-Akt pathway involved in necrosis induction, apoptosis /Phase I human clinical trial (Elisidepsin: phase II) |
IC50: 0.162–0.288 μM (colon), 0.135 μM (A549), 0.162 μM (H5578T), 0.479 μM (HS-578T) | [142,143,144,145,146,147,148,149,150,151,152,153,154,155] |
| Keenamide A (102) | Mollusk: Pleurobranchus forskalii | Cyclic hexapeptide | Cytotoxicity /in vitro only |
IC50: 2.5 μg/mL (P388, A549, MEL-20), 5 μg/mL (HT29) | [156] |
| Kulokekahilide-2 (103) | Mollusk: Philinopsis speciosa | Cyclic depsipeptide | Cytotoxicity /in vitro only |
IC50: 4.2–59.1 nM (P388, SKOV-3, MDA-MB-435, A-10) | [157] |
| Ziconotide (104) | Mollusk: Conus magus | Linear peptide | Selective N-type calcium channel blocker/FDA approved | IC50: 100 nM (HEK), 10 nM (IMR32) | [158,159,160,161] |
| Pardaxin (105) | Fish: Pardachirus marmoratus | Linear peptide | Caspase-dependent and ROS-mediated Apoptosis /active in animal |
IC90: 13 μg/mL (NH-11) | [162,163] |
| YALRAH (106) | Fish: Setipinna taty | Linear peptide | Antiproliferative activity/in vitro only |
IC50: 11.1 μM (PC3) | [164] |