Table I. 2005-6 Antitumour pharmacology of marine natural products with established mechanisms of action.
| Compound | Organism | Chemistry | Experimental or clinical model1 | Mechanism of action2 | Country3 | Ref. |
|---|---|---|---|---|---|---|
| aaptamine | Sponge | Alkaloid | HU osteosarcoma cell line | Induction of p21 gene and G2/M cell cycle arrest | INDO, JAPN | (90) |
| agosterol A | Sponge | Steroid | Insect cell expression of MRP1 wild type or mutants | [I125]-azido agosterol A binding to MRP1 abolished by ICL5 & ICL7 domain mutations | JAPN | (11) |
| alkylpyridinium salts | Sponge | Alkaloid | HU adenocarcinoma cell lines | Induction of apoptosis and reduced cell adhesion | ITA, SLO | (91) |
| aplidine | Ascidian | Depsipeptide | MU fibroblast cell line | Oxidation and inactivation of low molecular weight-protein tyrosine phosphatase activity | ITA, SPA | (12) |
| HU thyroid cancer cells | Cytostatic, blocks G1 phase of cell cycle, reduction of cyclin D1, cdk4 and p21 protein levels | SPA | (13) | |||
| Fas-positive and deficient HU leukemia cell line | Apoptosis promoted by concentration of death receptors, adaptors & signaling molecules in lipid rafts | SPA | (15) | |||
| HU-breast cancer cell line | JNK-dependent apoptosis affected by glutathione homeostasis, Rac1 GTPase activation & MKP-1 phosphatase | GER, SPA | (17) | |||
| aplyronine A | Sea hare | Macrolide | Synchrotron radiation method | Binding to hydrophobic cleft in actin molecule involving trimethylserine moiety | JAPN | (92) |
| ascididemin | Ascidian | Alkaloid | Assessment of DNA binding | Enhanced binding to telomeric DNA quadruplex | FRA, BEL | (21) |
| bastadin 6 | Sponge | Alkaloid | HU epidermoid carcinoma & leukemia cell lines | Inhibition of angiogenesis in vitro and in vivo involves apoptosis | JAPN | (93) |
| bistramide A | Ascidian | Polyketide | Depolymerization of F-actin, inhibition of G-actin polymerization, binding to actin subdomains 1 and 3 | USA | (27;28) | |
| bromovulone III | Soft coral | Prostanoid | HU hepatocarcinoma cell line | Apoptosis and endoplasmic reticulum stress, activation of caspase-12 | TAIW | (29) |
| Hormone-resistant prostate cancer cell line | Apoptosis via induction of Fas clustering and caspase-8/Bid/caspase-9 cascade | TAIW | (30) | |||
| bryostatin-1 | Bryozoan | Macrolide | HU prostate cancer cell lines | Apoptosis induction enhanced by PKCε overexpression | USA | (31) |
| HU cervical carcinoma cells | Enhanced cisplatin sensitivity associated to PKCδ regulation | USA | (32) | |||
| HU monocytic cell lines | Transcriptional and posttranscriptional regulation of IFNγ receptor 2 | USA | (35) | |||
| MU keratinocytes | Modulation of RasGRP1 receptor | USA | (34) | |||
| cephalostatin 1 | Tube worm | Steroid | HU Jurkat T cell line | Bcl-2 hyperphosphorylation independent of M-phase arrest and DNA damage | GER | (39) |
| HU Jurkat T cell line | Apoptosis induction via ER stress response signaling & caspase -4 & -9 activations | USA, GER | (40) | |||
| clavulone II | Soft coral | Prostanoid | HU leukemia cell line | G1 cell cycle arrest & apoptosis | TAIW | (94) |
| cortistatin A | Sponge | Alkaloid | HU normal and tumour cell lines | Selective inhibition of angiogenesis | JAPN, INDO | (95) |
| cryptophycins 52, 53, 249, & 309 | Bacterium | Depsipeptide | HU & MU glutathione metabolism | Cytosolic GSTs metabolize C52 & C53 | USA | (41) |
| 13-deoxytedanolide | Sponge | Macrolide | Ribosomal binding and polypeptide synthesis | Binding to 80S ribosome & 60S subunit; inhibition of polypeptide elongation | JAPN | (96) |
| dictyostatin-1 | Sponge | Macrolide | HU ovarian adenocarcinoma cell lines | Tubulin binding, taxoid site binding and antiproliferative effects comparable to discodermolide | USA | (44) |
| dideoxypetrosynol A | Sponge | Polyacetylene fatty acid | HU monocytic leukemia | Induction of Cdk inhibitor p16 expression & down-regulation of pRB phosphorylation | S. KOR | (46) |
| discodermolide | Polyketide | Direct photoaffinity labeling | Binding to amino acid residues 305-359 in the S9-S10 loop in β-tubulin | USA | (47) | |
| HU tumour cell lines | Inhibition of hypoxia-inducible factor 1α | SPA, USA | (48) | |||
| HU lung, colon, breast and cervical carcinoma | Induction of accelerated senescence | USA | (49) | |||
| dolastatin 10 & 15 | Mollusc | Peptide | HU tumour panel and MU cell line | Antitumour action & DNA fragmentation time-dependent & less affected by P-gp | JAPN | (52) |
| ecteinascidin-743 (ET-743) | Ascidian | Isoquinoline alkaloid | NIH 3T3 fibroblasts and HU hepatoma cell lines | Cell-cycle promoters are selectively affected | ITA | (62) |
| Lipo-, leio-, osteo- and chondrosarcoma cell lines | Up-regulation of 86 genes, down-regulation of 244 genes, cDNA microarray analysis with 6,700 cancer genes | SPA | (69) | |||
| S. pombo yeast model system | ET-743 binding to Arg314 in a 46-amino acid region of DNA-binding domain of human nuclease FEN-1 | SPA | (127) | |||
| fucoxanthinol | Ascidian | Carotenoid | HU leukemia, breast and colon tumour cell lines | Induction of apoptosis and decrease in Bcl-2 protein | JAPN | (97) |
| geodiamolides | Sponge | Peptide | HU breast cancer cell lines | Disorganization of actin filaments | BRA, JAPN | (98) |
| geoditin A | Sponge | Triterpene | HU leukemia cell line | Reactive oxygen species generation and caspase-3 mediated apoptosis | CHI | (99) |
| halichondrin B analogue E7389 | Sponge/Synthetic | Macrolide derivative | HU breast tumour cell line | Suppression of microtubule dynamics both in vitro and in vivo | USA | (80) |
| HU tumour cell lines, molecular modeling | Proposed binding site on tubulin results in unstable, aberrant tubulin polymers | USA, NZEL | (81) | |||
| hemiasterlin analogue HTI-286 | Sponge/synthetic | Tripeptide | Molecular docking experiments | Binding to specific residues in the β-tubulin | USA | (82) |
| ircinin-1 | Sponge | Sesterterpene | HU melanoma cell line | G1 phase inhibition and apoptosis induction | S. KOR | (100) |
| jasplakinolide | Sponge | Depsipeptide | HU breast and lung cancer cell lines | Enhanced motility of A549 lung cancer cells but not MCF7 breast tumour cells | BEL | (83) |
| kahalalide F | Mollusk | Depsipeptide | HU vulval, hepatic, colon and breast carcinoma cell lines | ErbB3 protein and PI3K-Akt pathway involved in necrosis induction | SPA, NETH | (84) |
| lamellarin D | Mollusk | Alkaloid | HU and MU tumour cell lines | Apoptosis induced by effect on mitochondria at μM concentrations | FRA, SPA | (86) |
| laxaphycins A & B | Bacterium | Cyclic peptides | HU lymphoblastic cell lines | Increased polyploidy by putative topoisomerase II alterations | FRA, BEN | (101) |
| leptosins C & F | Fungus | Alkaloid | HU lymphoblastoid cell line | DNA topoisomerase I & II inhibition, apoptosis induction & Akt/PKB inactivation | JAPN | (102) |
| ningalins | Ascidian/synthetic | Alkaloid | HU leukemia and breast cancer cell lines | Inhibition of PgP and MDR-reversing activity | USA | (103) |
| onnamide A | Sponge | Polyketide | HU leukemia cell line | Protein synthesis inhibition, activation of stress-activated protein kinases & apoptosis | JAPN | (104) |
| pateamine A | Sponge | Macrolide | HU T cell leukemia | Sequestration of RNA helicase elF4A inhibiting translation initiation | CAN, NZEL, USA | (87) |
| peloruside A | Sponge | Macrolide | HU breast cancer cell line | Synergistic effect with taxoid site drugs but not with laulimalide | NZEL, UK, USA | (88) |
| philinopside A | Sea cucumber | Saponin | HU adenocarcinoma cell lines | Inhibition of angiogenesis and receptor tyrosine kinases | CHI | (105) |
| psammaplin A | Sponge | Alkaloid | HU tumour cell lines | Activation of PPARγ and apoptosis induction | USA | (89) |
| salinosporamide A | Bacterium | Alkaloid | HU tumour cell lines | SAR studies revealed importance of chloroethyl group | USA | (106) |
| stellettin A | Sponge | Triterpene | HU leukemia cell line | Induction of oxidative stress & FasL-caspase 3 apoptotic pathway | CHI | (107) |
| strobilinin-felixinin | Sponge | Sesterterpene | HU tumour cell line | Cell cycle S phase arrest & inhibition of topoisomerase I and pol α-primase | S.KOR | (108) |
| variolin B | Sponge | Alkaloid | HU colon, leukemia & ovarian cell lines | Inhibition of cyclin-dependent kinases and apoptosis induction | FRA, ITA, SPA | (109) |
| verrucarin A | Fungus | Macrolide | HU leukemia cell lines | Inhibition of MAP kinase, enhanced p38 & JNK phosphorylation | JAPN | (110) |
1
Experimental or clinical model: HU: human; MU; murine;
2
Mechanism of action: SAR: Structure-activity relationship
3
Country: BEL: Belgium, BEN: Benin, BRA: Brazil, CAN: Canada, CHI: China, FRA: France, GER: Germany, INDO: Indonesia, ITA: Italy, JAPN: Japan, NETH: The Netherlands, NZEL: New Zealand, S.KOR: South Korea, SLO: Slovenia, SPA: Spain, TAIW: Taiwan, UK: United Kingdom.