| REVIEW |
|
|
|
|
|
Marine natural products as a source of novel anticancer drugs: an updated review (2019-2023) |
| Hesham R. El-Seedi1,2,3,4, Mohamed S. Refaey5, Nizar Elias6, Mohamed F. El-Mallah4, Faisal M. K. Albaqami7, Ismail Dergaa8, Ming Du9, Mohamed F. Salem10, Haroon Elrasheid Tahir11, Maria Dagliaa2,12, Nermeen Yosri13,14, Hongcheng Zhang15, Awg H. El-Seedi16, Zhiming Guo13, Shaden A. M. Khalifa2,17 |
1. Department of Chemistry, Faculty of Science, Islamic University of Madinah, 42351, Madinah, Saudi Arabia;
2. International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang, 212013, China;
3. International Joint Research Laboratory of Intelligent Agriculture and Agri-Products Processing, Jiangsu Education Department, Jiangsu University, Nanjing, 210024, China;
4. Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Kom, 31100107, Egypt;
5. Department of Pharmacognosy, Faculty of Pharmacy, University of Sadat City, Sadat City, 32897, Egypt;
6. Department of Laboratory Medicine, Faculty of Medicine, University of Kalamoon, P. O. Box 222, Dayr Atiyah, Syria;
7. Biology Department, Faculty of Science, Islamic University of Madinah, 42351, Madinah, Saudi Arabia;
8. Primary Health Care Corporation (PHCC), Doha, Qatar;
9. School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian, 116034, China;
10. Department of Environmental Biotechnology, Genetic Engineering and Biotechnology Research Institute, GEBRI, University of Sadat City, P. O. Box:79, Sadat City, Egypt;
11. Agricultural Product Processing and Storage Lab, School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, Jiangsu, China;
12. Department of Pharmacy, University of Napoli Federico II, Via D. Montesano 49, 80131, Naples, NA, Italy;
13. School of Food and Biological Engineering, Jiangsu University, Zhenjiang, 212013, China;
14. Chemistry Department of Medicinal and Aromatic Plants, Research Institute of Medicinal and Aromatic Plants (RIMAP), Beni-Suef University, Beni-Suef, 62514, Egypt;
15. State Key Laboratory of Resource Insects, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing, 100093, China;
16. International IT College of Sweden Stockholm, Arena Academy, H?lsobrunnsgatan 6, 11361, Stockholm, Sweden;
17. Psychiatry and Neurology Department, Capio Saint G?ran's Hospital, Sankt G?ransplan 1, 112 19, Stockholm, Sweden |
|
|
|
|
Abstract Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications, particularly in oncology. This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023. With a focus on recent research findings, the review explores the rich biodiversity of marine organisms, including sponges, corals, algae, and microorganisms, which have yielded numerous compounds exhibiting promising anticancer properties. Emphasizing the multifaceted mechanisms of action, the review discusses the molecular targets and pathways targeted by these compounds, such as cell cycle regulation, apoptosis induction, angiogenesis inhibition, and modulation of signaling pathways. Additionally, the review highlights the innovative strategies employed in the isolation, structural elucidation, and chemical modification of marine natural products to enhance their potency, selectivity, and pharmacological properties. Furthermore, it addresses the challenges and opportunities associated with the development of marine-derived anticancer drugs, including issues related to supply, sustainability, synthesis, and clinical translation. Finally, the review underscores the immense potential of marine natural products as a valuable reservoir of novel anticancer agents and advocates for continued exploration and exploitation of the marine environment to address the unmet medical needs in cancer therapy
|
| Keywords
Marine natural products
Microorganism
Anticancer
Clinical trials
Drugs
|
|
Corresponding Authors:
Hesham R. El-Seedi, E-mail:elseedi_99@yahoo.com;Faisal M. K. Albaqami, E-mail:falbaqami@iu.edu.sa;Shaden A. M. Khalifa, E-mail:shaden.khalifa@regionstockholm.se
E-mail: elseedi_99@yahoo.com;falbaqami@iu.edu.sa;shaden.khalifa@regionstockholm.se
|
|
Issue Date: 17 May 2025
|
|
|
[1] Hulvat MC. Cancer incidence and trends. Surg Clin. 2020;100:469-81.
[2] Falzone L, Salomone S, Libra M. Evolution of cancer pharmacological treatments at the turn of the third millennium. Front Pharmacol. 2018;9:1300.
[3] Cruz-Reyes N, Radisky DC. Inflammation, infiltration, and evasion—tumor promotion in the aging breast. Cancers. 2023;15:1836.
[4] WHO. Cancer. 2022.
[5] Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-49.
[6] Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17-48.
[7] Tenore G, et al. Tobacco, alcohol and family history of cancer as risk factors of oral squamous cell carcinoma: case-control retrospective study. Appl Sci. 2020;10:3896.
[8] An S-Y, et al. Obesity is positively related and tobacco smoking and alcohol consumption are negatively related to an increased risk of thyroid cancer. Sci Rep. 2020;10:19279.
[9] Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Drug Resist Combat Drug Resist Cancer. 2019;2:141-60.
[10] Yosri N, et al. Marine organisms: pioneer natural sources of polysaccharides/proteins for green synthesis of nanoparticles and their potential applications. Int J Biol Macromol. 2021;193:1767-98.
[11] El-Seedi HR, et al. Exploring natural products-based cancer therapeutics derived from Egyptian flora. J Ethnopharmacol. 2021;269:113626.
[12] Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Marine natural products. Nat Prod Rep. 2021;38:362-413.
[13] Carroll AR, Copp BR, Davis RA, Keyzers RA, Prinsep MR. Marine natural products. Nat Prod Rep. 2023;40:275-325.
[14] Lu W-Y, Li H-J, Li Q-Y, Wu Y-C. Application of marine natural products in drug research. Bioorg Med Chem. 2021;35:116058.
[15] El-Seedi HR, et al. Review of marine cyanobacteria and the aspects related to their roles: chemical, biological properties, nitrogen fixation and climate change. Mar Drugs. 2023;21:439.
[16] Montuori E, Hyde CAC, Crea F, Golding J, Lauritano C. Marine natural products with activities against prostate cancer: recent discoveries. Int J Mol Sci. 2023;24:1435.
[17] Khalifa SAM, et al. Marine natural products: a source of novel anticancer drugs. Mar Drugs. 2019;17:491.
[18] Hentschel U, Piel J, Degnan SM, Taylor MW. Genomic insights into the marine sponge microbiome. Nat Rev Microbiol. 2012;10:641-54.
[19] Perdicaris S, Vlachogianni T, Valavanidis A. Bioactive natural substances from marine sponges: new developments and prospects for future pharmaceuticals. Nat Prod Chem Res. 2013;1:2329-6836.
[20] Radjasa OK, et al. Highlights of marine invertebrate-derived biosynthetic products: their biomedical potential and possible production by microbial associants. Bioorg Med Chem. 2011;19:6658-74.
[21] Altmann K-H. Drugs from the oceans: marine natural products as leads for drug discovery. Chimia. 2017;71:646.
[22] Cappello E, Nieri P. From life in the sea to the clinic: the marine drugs approved and under clinical trial. Life. 2021;11:1390.
[23] De AK, et al. A natural quinazoline derivative from marine sponge Hyrtios erectus induces apoptosis of breast cancer cells via ROS production and intrinsic or extrinsic apoptosis pathways. Mar Drugs. 2019;17:658.
[24] Jomori T, Setiawan A, Sasaoka M, Arai M. Cytotoxicity of new diterpene alkaloids, ceylonamides G-I, isolated from Indonesian marine sponge of Spongia sp. Nat Prod Commun. 2019;14:1934578X19857294.
[25] Sakai R, et al. Soritesidine, a novel proteinous toxin from the okinawan marine sponge Spongosorites sp. Mar Drugs. 2019;17:216.
[26] Wu Y, et al. Phakefustatins A-C: kynurenine-bearing cycloheptapeptides as RXRα modulators from the marine sponge Phakellia fusca. Org Lett. 2020;22:6703-8.
[27] Ki D-W, et al. New cytotoxic polyacetylene amides from the Egyptian marine sponge Siphonochalina siphonella. Fitoterapia. 2020;142:104511.
[28] Surti M, et al. Ilimaquinone (marine sponge metabolite) induces apoptosis in HCT-116 human colorectal carcinoma cells via mitochondrial-mediated apoptosis pathway. Mar Drugs. 2022;20:582.
[29] Wang Z, et al. Kalihioxepanes A—G: seven kalihinene diterpenoids from marine sponge Acanthella cavernosa collected off the south China Sea. Chin J Chem. 2022;40:1785-92.
[30] Carpi S, et al. Pro-apoptotic activity of the marine sponge Dactylospongia elegans metabolites pelorol and 5-epi-ilimaquinone on human 501Mel melanoma cells. Mar Drugs. 2022;20:427.
[31] Zhou M, et al. 12-deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine sponge Hippospongia sp., induces HeLa cells apoptosis via MAPK/ERK Pathway and modulates nuclear receptor Nur77. Mar Drugs. 2020;18:643.
[32] Ki D-W, et al. New cytotoxic polyacetylene alcohols from the Egyptian marine sponge Siphonochalina siphonella. J Nat Med. 2020;74:409-14.
[33] Yu H-B, et al. Cytotoxic meroterpenoids from the marine sponge Dactylospongia elegans. Nat Prod Res. 2021;35:1620-6.
[34] Tran HN, Kim MJ, Lee Y-J. Scalarane sesterterpenoids isolated from the marine sponge Hyrtios erectus and their cytotoxicity. Mar Drugs. 2022;20:604.
[35] Chikamatsu S, et al. In vitro and in vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells. Cancer Med. 2019;8:5662-72.
[36] Cheng S-Y, et al. Anti-invasion and antiangiogenic effects of stellettin B through inhibition of the Akt/Girdin signaling pathway and VEGF in glioblastoma cells. Cancers. 2019;11:220.
[37] Feng C-W, et al. In vitro and in vivo neuroprotective effects of stellettin B through anti-apoptosis and the Nrf2/HO-1 pathway. Mar Drugs. 2019;17:315.
[38] Ahn J-H, Woo J-H, Rho J-R, Choi J-H. Anticancer activity of Gukulenin A isolated from the marine sponge Phorbas gukhulensis in vitro and in vivo. Mar Drugs. 2019;17:126.
[39] Stanojkovic TP, et al. Evaluation of in vitro cytotoxic potential of avarol towards human cancer cell lines and in vivo antitumor activity in solid tumor models. Molecules. 2022;27:9048.
[40] Mohamadkhani A. Gene cluster analysis of marine bacteria seeking for natural anticancer products. Jundishapur J Nat Pharm Prod. 2021;16: e104665.
[41] Kačar D, et al. Identification of trans-AT polyketide clusters in two marine bacteria reveals cryptic similarities between distinct symbiosis factors. Environ Microbiol. 2021;23:2509-21.
[42] Kristoffersen V, et al. Two novel lyso-ornithine lipids isolated from an arctic marine Lacinutrix sp. bacterium. Molecules. 2021;26:5295.
[43] Malhão F, et al. Cytotoxic and antiproliferative effects of preussin, a hydroxypyrrolidine derivative from the marine sponge-associated fungus Aspergillus candidus KUFA 0062, in a panel of breast cancer cell lines and using 2D and 3D cultures. Mar Drugs. 2019;17:448.
[44] Farha AK, Hatha AM. Bioprospecting potential and secondary metabolite profile of a novel sediment-derived fungus Penicillium sp. ArCSPf from continental slope of Eastern Arabian Sea. Mycology. 2019;10:109-17.
[45] Liu L, et al. Penicindopene A, a new indole diterpene from the deep-sea fungus Penicillium sp. YPCMAC1. Nat Prod Res. 2019;33:2988-94.
[46] Cheng Z, et al. Three new cyclopiane-type diterpenes from a deep-sea derived fungus Penicillium sp. YPGA11 and their effects against human esophageal carcinoma cells. Bioorg Chem. 2019;91:103129.
[47] Fan B, et al. Pyrenosetin D, a new pentacyclic decalinoyltetramic acid derivative from the algicolous fungus Pyrenochaetopsis sp. FVE-087. Mar Drugs. 2020;18:281.
[48] Chen J-J, et al. Highly oxygenated constituents from a marine alga-derived fungus Aspergillus giganteus NTU967. Mar Drugs. 2020;18:303.
[49] Dezaire A, et al. Secondary metabolites from the culture of the marine-derived fungus Paradendryphiella salina PC 362H and evaluation of the anticancer activity of its metabolite hyalodendrin. Mar Drugs. 2020;18:191.
[50] Parthasarathy R, et al. Molecular profiling of marine endophytic fungi from green algae: assessment of antibacterial and anticancer activities. Process Biochem. 2020;96:11-20.
[51] Ma M, Ge H, Yi W, Wu B, Zhang Z. Bioactive drimane sesquiterpenoids and isocoumarins from the marine-derived fungus Penicillium minioluteum ZZ1657. Tetrahedron Lett. 2020;61:151504.
[52] Bae SY, et al. Antitumor activity of asperphenin A, a lipopeptidyl benzophenone from marine-derived Aspergillus sp. fungus, by inhibiting tubulin polymerization in colon cancer cells. Mar Drugs. 2020;18:110.
[53] Wang F, et al. Waikikiamides A-C: complex diketopiperazine dimer and diketopiperazine-polyketide hybrids from a hawaiian marine fungal strain Aspergillus sp. FM242. Org Lett. 2020;22:4408-12.
[54] Tang R, Zhou D, Kimishima A, Setiawan A, Arai M. Selective cytotoxicity of marine-derived fungal metabolite (3S,6S)-3,6-dibenzylpiperazine-2,5-dione against cancer cells adapted to nutrient starvation. J Antibiot. 2020;73:873-5.
[55] Jiang L-L, et al. Cytotoxic secondary metabolites isolated from the marine alga-associated fungus Penicillium chrysogenum LD-201810. Mar Drugs. 2020;18:276.
[56] Zhang J, et al. Cytotoxic secondary metabolites from a sea-derived fungal strain of Hypoxylon rubiginosum FS521. Chin J Org Chem. 2020;40:1367.
[57] Feng J, et al. FGFC1 exhibits anti-cancer activity via inhibiting NF-κB signaling pathway in EGFR-mutant NSCLC cells. Mar Drugs. 2022;20:76.
[58] Chen L, et al. Isolation of 4,4'-bond secalonic acid D from the marine-derived fungus Penicillium oxalicum with inhibitory property against hepatocellular carcinoma. J Antibiot. 2019;72:34-44.
[59] Jayawardena TU, et al. Antiproliferative and apoptosis-inducing potential of 3$β$-hydroxy-$Δ$5-steroidal congeners purified from the soft coral Dendronephthya putteri. J Oceanol Limnol. 2019;37:1382-92.
[60] Tseng WR, et al. Bioactive capnosanes and cembranes from the soft coral Klyxum flaccidum. Mar Drugs. 2019;17:9-11.
[61] Hegazy MEF, et al. Sarcoehrenbergilides D-F: cytotoxic cembrene diterpenoids from the soft coral: Sarcophyton ehrenbergi. RSC Adv. 2019;9:27183-9.
[62] Huang C, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506.
[63] Alarif WM, et al. Two new xeniolide diterpenes from the soft coral Xenia umbellata; displayed anti proliferative effects. Pharmacogn Mag. 2020;16:774-9.
[64] Yang F, et al. Uncommon nornardosinane, seconeolemnane and related sesquiterpenoids from Xisha soft coral Litophyton nigrum. Bioorg Chem. 2020;96:103636.
[65] Huang TY, et al. New hydroquinone monoterpenoid and cembranoid-related metabolites from the soft coral Sarcophyton tenuispiculatum. Mar Drugs. 2021;19:8.
[66] Lin YC, et al. Targeted isolation of xenicane diterpenoids from Taiwanese soft coral Asterospicularia laurae. Mar Drugs. 2021;19:123.
[67] Mohamed TA, et al. A new cembranoid from the Red Sea soft coral Sarcophyton acutum. Nat Prod Res. 2024;38:512.
[68] Welsch JT, et al. Tuaimenals B-H, merosesquiterpenes from the Irish deep-sea soft coral Duva florida with bioactivity against cervical cancer cell lines. J Nat Prod. 2023;86:182.
[69] Ghandourah MA. Cytotoxic ketosteroids from the Red Sea soft coral Dendronephthya sp. Open Chem. 2023;21:4-9.
[70] Zhang J, et al. Seven new lobane diterpenoids from the soft coral Lobophytum catalai. Mar Drugs. 2023;21:451.
[71] Chao CH, et al. Cembranolides and related constituents from the soft coral Sarcophyton cinereum. Molecules. 2022;27:1760.
[72] Nayaka S, et al. A potential bioactive secondary metabolites and antimicrobial efficacy of Streptomyces thermocarboxydus strain KSA-2, isolated from Kali River, Karwar. Curr Res Microbiol Infect. 2020;1:5-13.
[73] Fahmy NM, Abdel-Tawab AM. Isolation and characterization of marine sponge-associated Streptomyces sp. NMF6 strain producing secondary metabolite(s) possessing antimicrobial, antioxidant, anticancer, and antiviral activities. J Genet Eng Biotechnol. 2021;19:102.
[74] Nadar Rajivgandhi G, et al. Molecular identification and structural detection of anti-cancer compound from marine Streptomyces akiyoshiensis GRG 6 (KY457710) against MCF-7 breast cancer cells. J King Saud Univ Sci. 2020;32:3463-9.
[75] Bhattacharya B, Mukherjee S. Cancer therapy using antibiotics. J Cancer Ther. 2015;06:849-58.
[76] Demain AL, Vaishnav P. Natural products for cancer chemotherapy. Microb Biotechnol. 2011;4:687-99.
[77] Al-Ansari M, Kalaiyarasi M, Almalki MA, Vijayaraghavan P. Optimization of medium components for the production of antimicrobial and anticancer secondary metabolites from Streptomyces sp. AS11 isolated from the marine environment. J King Saud Univ Sci. 2020;32:1993-8.
[78] Song Y, et al. Chlorinated bis-indole alkaloids from deep-sea derived Streptomyces sp. SCSIO 11791 with antibacterial and cytotoxic activities. J Antibiot. 2020;73:542-7.
[79] Nair V, et al. Verrucosamide, a cytotoxic 1,4-thiazepane-containing thiodepsipeptide from a marine-derived actinomycete. Mar Drugs. 2020;18:549.
[80] Marchbank DH, Ptycia-Lamky VC, Decken A, Haltli BA, Kerr RG. Guanahanolide A, a meroterpenoid with a sesterterpene skeleton from coral-derived Streptomyces sp. Org Lett. 2020;22:6399-403.
[81] Riccio G, et al. Jellyfish as an alternative source of bioactive antiproliferative compounds. Mar Drugs. 2022;20:350.
[82] Riccio G, et al. Bioactivity screening of Antarctic sponges reveals anticancer activity and potential cell death via ferroptosis by mycalols. Mar Drugs. 2021;19:459.
[83] Cruz C, et al. Multicenter phase II study of lurbinectedin in BRCA-mutated and unselected metastatic advanced breast cancer and biomarker assessment substudy. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36:3134-43.
[84] Jimenez PC, et al. Enriching cancer pharmacology with drugs of marine origin. Br J Pharmacol. 2020;177:3-27.
[85] Deeks ED. Polatuzumab vedotin: first global approval. Drugs. 2019;79:1467-75.
[86] Sehn LH, et al. Polatuzumab vedotin in relapsed or refractory diffuse large b-cell lymphoma. J Clin Oncol Off J Am Soc Clin Oncol. 2020;38:155-65.
[87] Rosenberg JE, et al. Pivotal trial of enfortumab vedotin in urothelial carcinoma after platinum and anti-programmed death 1/programmed death ligand 1 therapy. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37:2592-600.
[88] Lonial S, et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. Lancet Oncol. 2020;21:207-21. |
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
| |
Shared |
|
|
|
|
| |
Discussed |
|
|
|
|
