Yabancı Kökenli Makroalglerin Anti-Kanser Bileşik Kaynağı Olarak Potansiyeli: Ekoloji ve Farmakoloji Arasında Köprü

Abstract

Akdeniz’de iklim değişikliğinin önemli etkilerinden biri de yabancı türlerin varlığındaki artıştır. Bu türler yalnızca biyoçeşitlilik için değil, aynı zamanda ekonominin çeşitli sektörleri için de ciddi tehditler oluşturmaktadır. Bu türleri kontrol etme yöntemlerinden biri ekosistemden uzaklaştırılmalarıdır. Ancak, bu uzaklaştırma işlemi, tür ekonomik değeri olan bir özelliğe sahipse anlam kazanmaktadır. Bu çalışmada, beş farklı bölgeden toplanan beş yabancı makroalg türünün antikanser uygulamalarda potansiyel kullanımı, topoizomeraz inhibisyon aktivitesi yoluyla araştırılmıştır. Topoizomeraz I ve II enzim inhibisyon testlerinin ardından, interkalasyon aktivitesi analizleri gerçekleştirilmiştir. Tüm türlerin her iki enzimi inhibe etme potansiyeline sahip olduğu bulunmuştur. Ancak, yalnızca bir türde interkalasyon aktivitesi gözlemlenmiştir. Elde edilen sonuçlara göre, beş tür arasında en umut verici farmasötik aday, tüm aktivite analizlerinde güçlü bir performans sergileyen kırmızı alg Grateloupia turuturu olarak belirlenmiştir.

Keywords

• Topoizomeraz
• alg
• yabancı tür
• Akdeniz
• doğal ürün

Non-Indigenous Macroalgae as a Source of Anti-Cancer Agents: Bridging Ecology and Pharmacology

Abstract

One of the significant impacts of climate change is the increasing presence of non-native species in the Mediterranean Sea. These species pose significant threats not only to biodiversity but also to various sectors of the economy. One of the methods to control these species—although costly and labor-intensive—is their eradication from the ecosystem. However, this removal process is only worthwhile if the species possesses a characteristic with economic value, justifying the financial and labor investment. In this study, the potential use of five different alien macroalgae species, collected from five distinct locations, in anticancer applications was investigated through topoisomerase inhibition activity. Following topoisomerase I and II enzyme inhibition assays, intercalation activity analyses were conducted. All species were found to have the potential to inhibit both enzymes. However, intercalation activity was observed in only one species. Based on the results, among the five species, the most promising pharmaceutical candidate was identified as the red alga Grateloupia turuturu, which exhibited strong performance across all activity analyses.

Keywords

• Topoisomerase
• seaweed
• alien species
• mediterranean sea
• natural product

References

1. References [1] N. Myers, R. A. Mittermeier, C. G. Mittermeier, G. A. B. da Fonseca, J. Kent, Biodiversity hotspots for conservation priorities, Nature, 403 (2000) 853–858.
2. [2] A. Zenetos, S. Gofas, M. Verlaque, M. E. Çinar, J. E. G. Raso et al., Alien species in the Mediterranean Sea by 2010: a contribution to the application of European Union’s Marine Strategy Framework Directive (MSFD). Part I. Spatial distribution, Mediterr. Mar. Sci., 11 (2010) 381–493.
3. [3] O. Gonulal, C. Dalyan, N. B. Kesici, I. Tuney, Non-Indigenous Species Gaining Advantage with Climate Change in the Aegean Sea,” in Ecological Dynamics in the Face of Climate Change—Exploring Organisms, Habitats, and Behavioral Adaptations (Eds.: N. Doğruöz Güngör, E. Arslan Aydoğdu), Nobel Publishing, Istanbul, Turkiye, 2024, pp. 133–172.
4. [4] R. N. Mack, D. Simberloff, W. M. Lonsdale, H. Evans, M. Clout et al., Biotic invasions: causes, epidemiology, global consequences, and control, Ecol. Appl., 10 (2000) 689–710.
5. [5] B. Schaffelke, J. E. Smith, C. L. Hewitt, Introduced macroalgae – a growing concern, J. Appl. Phycol., 18 (2006) 529–541.
6. [6] B. S. Galil, Loss or gain? Invasive aliens and biodiversity in the Mediterranean Sea, Mar. Pollut. Bull., 55 (2007) 314–322.
7. [7] D. Edelist, G. Rilov, D. Golani, J. T. Carlton, E. Spanier, Restructuring the sea: profound shifts in the world’s most invaded marine ecosystem, Divers. Distrib., 19 (2013) 69–77.
8. [8] S. Katsanevakis, I. Wallentinus, A. Zenetos, E. Leppäkoski, M. E. Çinar et al., Impacts of invasive alien marine species on ecosystem services and biodiversity: a pan-European review, Aquat. Invasions, 9 (2014 ) 391–423.

9. [9] M. Wesselmann, I. E. Hendriks, M. Johnson, G. Jordà, F. Mineur et al., Increasing spread rates of tropical non-native macrophytes in the Mediterranean Sea, Glob. Change Biol., 30 (2024) e17249.
10. [10] R. Early, B. A. Bradley, J. S. Dukes, J. J. Lawler, J. D. Olden et al., Global threats from invasive alien species in the twenty-first century and national response capacities, Nat. Commun., 7 (2016) 12485.
11. [11] S. L. Williams, J. E. Smith, A global review of the distribution, taxonomy, and impacts of introduced seaweeds Annu. Rev. Ecol. Evol. Syst., 38 (3007) 327–359.
12. [12] A. Zenetos, M. Galanidi, I. Giovos, N. Doumpas, M. E. Çinar et al., Established non-indigenous species increased by 40% in 11 years in the Mediterranean Sea, Mediterr. Mar. Sci., 23 (2022) 679–698.
13. [13] P. Panayotidis, K. Tsiamis, “Seaweed flora and vegetation of the Aegean Sea,” in The Aegean Sea Environment, Vol. 1 (Eds.: C. L. Anagnostou, A. G. Kostianoy, I. Mariolakos, G. Tsaltas), 1st edn., Springer, Cham, Switzerland, 2021, pp. 291–301.
14. [14] M. Verlaque, C. Durand, J. M. Huisman, C. F. Boudouresque, Y. le Parco, On the identity and origin of the Mediterranean invasive Caulerpa racemosa (Caulerpales, Chlorophyta), Eur. J. Phycol., 38 (2003) 325–329.
15. [15] M. Montefalcone, C. Morri, V. Parravicini, C. N. Bianchi, A tale of two invaders: divergent spreading kinetics of the alien green algae Caulerpa taxifolia and Caulerpa cylindracea, Biol. Invasions, 17 (2015) 2717–2728.
16. [16] J. Klein, M. Verlaque, The Caulerpa racemosa invasion: a critical review, Mar. Pollut. Bull., 56 (2008) 205–225.
17. [17] A. Fortic, Z. Almajid, A. Badreddine, J. C. Baez, A. Belmonte-Gallegos et al., New records of introduced species in the Mediterranean Sea (April 2023), Mediterr. Mar. Sci., 24 (2023) 182–202.
18. [18] M. Verlaque, S. Ruitton, F. Mineur, C. F. Boudouresque, Macrophytes” in CIESM Atlas of Exotic Species in the Mediterranean, Vol. 4 (Ed.: F. Briand), CIESM Publishers, Monaco 2015, pp. 360.
19. [19] MSFD, “European Union, Commission Decision (EU) 2017/848” 2017, http://data.europa.eu/eli/dec/2017/848/oj, accessed 10 September 2025.
20. [20] IAS, “European Union, Regulation (EU) No 1143/2014” 2014, https://ec.europa.eu/jrc/en/science-update/best-options-control-marine-invasive-species, accessed 10 September 2025.
21. [21] S. J. Green, E. D. Grosholz, Functional eradication as a framework for invasive species control, Front. Ecol. Environ., 19 (2021) 98–107.
22. [22] P. Susano, J. Silva, C. Alves, A. Martins, S. Pinteus et al., Mitigating the negative impacts of marine invasive species—Sargassum muticum—a key seaweed for skincare products development, Algal Res., 62 (2022) 102634.
23. [23] J. J. Champoux, R. Dulbecco, An activity from mammalian cells that untwists superhelical DNA: a possible swivel for DNA replication (polyoma-ethidium bromide-mouse-embryo cells-dye binding assay), PNAS, 69 (1972) 143–146.
24. [24] J. Wang, Interaction between DNA and an Escherichia coli protein ω, J. Mol. Biol., 55 (1971) 523–533.
25. [25] J. C. Wang, Cellular roles of DNA topoisomerases: a molecular perspective, Nat. Rev. Mol. Cell. Biol., 3 (2002) 430–440.
26. [26] M. Yanagida, Basic mechanism of eukaryotic chromosome segregation, Philos. Trans. R. Soc. B., 360 (2005) 609–621.
27. [27] A. S. Belmont, Mitotic chromosome structure and condensation, Curr. Opin. Cell. Biol., 18 (2006) 632–638.
28. [28] J. L. Nitiss, Targeting DNA topoisomerase II in cancer chemotherapy, Nat. Rev. Cancer., 9 (2009) 338–350.
29. [29] M. Durand-Dubief, J. P. Svensson, J. Persson, K. Ekwall, Topoisomerases, chromatin and transcription termination, Transcription, 2 (2011) 66–70.
30. [30] S. M. Vos, E. M. Tretter, B. H. Schmidt, J. M. Berger, All tangled up: How cells direct, manage and exploit topoisomerase function, Nat. Rev. Mol. Cell Biol., 12 (2011) 827–841.
31. [31] C. K. Jain, H. K. Majumder, S. Roychoudhury, Natural Compounds as Anticancer Agents Targeting DNA Topoisomerases, Curr. Genomics, 18 (2017) 75–92.
32. [32] A. M. Fry, C. M. Chresta, S. M. Davies, M. C. Walker, A. L. Harris, et al., Relationship between topoisomerase II level and chemosensitivity in human tumor cell lines, Cancer Res., 51 (1991) 6592–6595.
33. [33] T. D. Pfister, W. C. Reinhold, K. Agama, S. Gupta, S. A. Khin, et al., Topoisomerase I levels in the NCI-60 cancer cell line panel determined by validated ELISA and microarray analysis and correlation with indenoisoquinoline sensitivity, Mol. Cancer Ther., 8 (2009) 1878–1884.
34. [34] M. E. Ashour, R. Atteya, S. F. El-Khamisy, Topoisomerase-mediated chromosomal break repair: an emerging player in many games, Nat. Rev. Cancer, 15 (2015) 137–151.
35. [35] T. Chen, Y. Sun, P. Ji, S. Kopetz, W. Zhang, Topoisomerase IIα in chromosome instability and personalized cancer therapy, Oncogene, 34 (2015) 4019–4031.
36. [36] A. K. McClendon, N. Osheroff, DNA topoisomerase II, genotoxicity, and cancer, Mutat. Res., 623 (2007) 83–97.
37. [37] J. E. Deweese, N. Osheroff, The DNA cleavage reaction of topoisomerase II: wolf in sheep’s clothing, Nucleic Acids Res., 37 (2009) 738–748.
38. [38] Y. Pommier, P. Pourquier, Y. Fan, D. Strumberg, Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme, Biochim. Biophys. Acta, 1400 (1998) 83–1058.
39. [39] A. C. Ketron, N. Osheroff, Phytochemicals as anticancer and chemopreventive topoisomerase II poisons, Photochem. Rev., 13 (2014) 19–35.
40. [40] N. Anand, D. Rachel, N. Thangaraju, P. Anantharaman, Potential of marine algae (sea weeds) as source of medicinally important compounds; in Evolving Trends in Plant Based Drug Discovery (Ed.: S. Rasool), Cambridge University Press, Cambridge, UK 2016, pp. 303–313.
41. [41] I. C. Nova, A. S. Oliveira, I. L. Bezerra, N. A. M. Ribeiro, L. F. Dias, et al., It comes from the sea: macroalgae-derived bioactive compounds with anti-cancer potential, Crit. Rev. Biotechnol., 43 (2023) 385–407.
42. [42] C. S. Vairappan, Potent antibacterial activity of halogenated metabolites from Malaysian red algae, Laurencia majuscule (Rhodomelaceae, Ceramiales), Biomol. Eng., 20 (2003) 255–259.
43. [43] W. Gul, M. T. Hamann, Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases, Life Sci., 78 (2005) 442–453.
44. [44] Y. X. Li, Y. Li, Z. J. Qian, M. M. Kim, S. K. Kim, In vitro antioxidant activity of 5-HMF isolated from marine red alga Laurencia undulata in free radical mediated oxidative systems, J. Microbiol. Biotechnol., 19 (2009) 1319–1327.
45. [45] S. Mohamed, S. N. Hashim, H. A. Rahman, Seaweeds: A sustainable functional food for complementary and alternative therapy, Trends Food Sci. Technol., 23 (2012) 83–96.
46. [46] J. Almeida, T. Ferreira, S. Santos, M. J. Pires, R. M. Gil da Costa, et al., The red seaweed Grateloupia turuturu prevents epidermal dysplasia in HPV16-transgenic mice Nutrients, 13 (2021) 4529.
47. [47] E. W. Prayogo, I. Sholikhah, S. Dej-adisai, R. Widyowati, Systematic Review of Green Seaweed Caulerpa racemosa as an Anti-Inflammatory Agent: Current Insights and Future Perspectives, J. Pharm. Pharm. Sci., 11 (2024) 156–173.
48. [48] Y. B. Kim, Y. G. Moon, M. S. Heo, Antioxidant and antimicrobial activities of seaweed, Ecklonia cava, J. Biotechnol., 136 (2008) 598.
49. [49] M. Cho, G. M. Park, S. N. Kim, T. Amna, S. Lee, et al., Glioblastoma-specific anticancer activity of pheophorbide a from the edible red seaweed Grateloupia elliptica, J. Microbiol. Biotechnol., 24 (2014) 346–353.
50. [50] E. Taskin, O. Aydogan, E. Cinar, M. Ozturk, Alien marine macrophytes in Turkey, Eur. J. Phycol., 46 (2011) 188.
51. [51] E. Taşkın, M. Özturk, Türkiye Deniz Algleri, Celal Bayar Üniversitesi, 2013.
52. [52] C. Rodríguez-Prieto, E. Ballesteros, F. Boisset, J. Afonso-Carrillo, Guía de las macroalgas y fanerógamas marinas del Mediterráneo occidental, Ediciones Omega, Barcelona, Spain, 2013. ISBN 978-84-282-1592-3.
53. [53] F. N. Onal, I. Ozturk, A. Kose, G. Der, E. Kilinc, et al., Comparative Evaluation of Polyphenol Contents and Biological Activities of Five Cistus L. Species Native to Turkey, J. Nat. Prod., 86 (2023) 1123–1135.
54. [54] Z. Topcu, Densitometric quantification of DNA topoisomers in ethidium bromide-stained agarose gels and chemiluminescence-detected X ray films, Acta Biochim. Pol., 47 (2000) 835–839.
55. [55] Z. Topcu, F. J. Castora, Mammalian mitochondrial DNA topoisomerase I preferentially relaxes supercoils in plasmids containing specific mitochondrial DNA sequences, Biochim. Biophys. Acta Gene Struct. Expr., 1628 (2003) 45–54.
56. [56] Y. Baran, S. Zencir, Z. Cakir, E. Ozturk, Z. Topcu, Imatinib-induced apoptosis: A possible link to topoisomerase enzyme inhibition, JBUON, 16 (2010) 141–147.
57. [57] A. Zenetos, P. Albano, E. L. Garcia, N. Stern, K. Tsiamis, M. Galanidi, Corrigendum to the Review Article: Established non-indigenous species increased by 40% in 11 years in the Mediterranean Sea, Mediterr. Mar. Sci., 23 (2022) 876–878.
58. [58] M. Borghini, H. Bryden, K. Schroeder, S. Sparnocchia, A. Vetrano, The Mediterranean is getting saltier, Ocean Sci. Discuss., 11 (2014) 735–752.
59. [59] L. Stabili, S. Fraschetti, M. I. Acquaviva, R. A. Cavallo, S. A. De Pascali, et al., The Potential Exploitation of the Mediterranean Invasive Alga Caulerpa cylindracea: Can the Invasion Be Transformed into a Gain?, Mar. Drugs, 14 (2016) 210.
60. [60] A. A. Mansur, M. T. Brown, R. A. Billington, The cytotoxic activity of extracts of the brown alga Cystoseira tamariscifolia (Hudson) Papenfuss, against cancer cell lines changes seasonally, J. Appl. Phycol., 32 (2020) 2419–2429.
61. [61] B. Aydın, Antibacterial activities of methanolic extracts of different seaweeds from Iskenderun Bay, Turkey, IJSM, 8 (2021) 120–126.
62. [62] Ö. Demirkiran, E. Erol, H. Şenol, İ. M. Kesdi, G. Ö. A. Toraman, E. Ş. Okudan, G. Topcu, Cytotoxic meroterpenoids from brown alga Stypopodium schimperi (Kützing) Verlaque & Boudouresque with comprehensive molecular docking & dynamics and ADME studies, Process Biochem., 136 (2024) 90–108.
63. [63] A. Kozak-Balkan, Determination of secondary metabolite from macroalgae and anti-cancer activities, PhD thesis, Ege University, Izmir, Turkiye, 2020
64. [64] E. Erol, M. D. Orhan, T. Avsar, A. Akdemir, E. S. Okudan, G. O. A. Toraman, G. Topcu, Anti-SARS-CoV-2 and cytotoxic activity of two marine alkaloids from green alga Caulerpa cylindracea Sonder in the Dardanelles, RSC Adv., 12 (2022) 29983.
65. [65] T. Nakatsu, B. N. Ravi, D. J. Faulkner, Antimicrobial constituents of Udotea flabellum, J. Org. Chem., 46 (1981) 2435–2438.
66. [66] M. L. M. Marques, F. B. Presa, R. L. S. Viana, M. S. S. P. Costa, M. O. R. Amorim, et al., Anti-thrombin, anti-adhesive, anti-migratory, and anti-proliferative activities of sulfated galactans from the tropical green seaweed Udotea flabellum, Mar. Drugs, 17 (2019) 5.
67. [67] R. Moo-Puc, D. Robledo, Y. Freile-Pelegrin, Enhanced antitumoral activity of extracts derived from cultured Udotea flabellum (Chlorophyta), eCAM 2011, 2011, 969275.
68. [68] I. Cardoso, J. Cotas, A. Rodrigues, D. Ferreira, N. Osório, et al., Extraction and Analysis of Compounds with Antibacterial Potential from the Red Alga Grateloupia turuturu, J. Mar. Sci. Eng., 7 (2019) 220.
69. [69] E. Plouguerné, C. Hellio, E. Deslandes, B. Véron, V. Stiger-Pouvre, Anti-microfouling activities in extracts of two invasive algae: Grateloupia turuturu and Sargassum muticum, Bot. Mar., 51 (2008) 202–208.
70. [70] N. García-Bueno, P. Decottignies, V. Turpin, J. Dumay, C. Paillard, et al., Seasonal antibacterial activity of two red seaweeds, Palmaria palmata and Grateloupia turuturu, on European abalone pathogen Vibrio harveyi, Aquat. Living Resour., 27 (2014) 83–89.
71. [71] A. G. Pereira, M. Fraga-Corral, P. Garcia-Oliveira, C. Lourenço-Lopes, M. Carpena, M. A. Prieto, J. Simal-Gandara, The use of invasive algae species as a source of secondary metabolites and biological activities: Spain as case-study, Mar. Drugs, 19 (2021) 178.
72. [72] M. Kendel, A. Couzinet-Mossion, M. Viau, J. Fleurence, G. Barnathan, G. Wielgosz-Collin, Seasonal composition of lipids, fatty acids, and sterols in the edible red alga Grateloupia turuturu, J. Appl. Phycol., 25 (2013) 425–432.
73. [73] M. Kendel, G. Barnathan, J. Fleurence, V. Rabesaotra, G. Wielgosz-Collin, Non-methylene interrupted and hydroxy fatty acids in polar lipids of the alga Grateloupia turuturu over the four seasons, Lipids, 48 (2013) 535–545.
74. [74] J. Kim, J. H. Choi, G. Ko, H. Jo, T. Oh, B. Ahn, T. Unno, Anti-Inflammatory Properties and Gut Microbiota Modulation of Porphyra tenera Extracts in Dextran Sodium Sulfate-Induced Colitis in Mice, Antioxidants, 9 (2020) 988.
75. [75] E. da Costa, T. Melo, M. Reis, P. Domingues, R. Calado, M. H. Abreu, M. R. Domingues, Polar Lipids Composition, Antioxidant and Anti-Inflammatory Activities of the Atlantic Red Seaweed Grateloupia turuturu, Mar. Drugs, 19 (2021) 414.
76. [76] B. Zengin, G. Ö. A. Toraman, R. S. Yanıkoğlu, F. Göç, H. Ö. Dinç, E. Ş. Okudan, H. Şenol, Chemical Contents and Bioactivities of Green Algae Ulva rigida C. Agardh Red Algae Grateloupia turuturu Yamada Extracts, Bezmialem. Sci., 12 (2024) 317–326.
77. [77] C. Cai, A. Anton, C. M. Duarte, S. Agusti, Spatial variations of nutrient and trace metal concentrations in macroalgae across blue carbon habitats of the Saudi Arabian Red Sea, Sci. Total Environ., 956 (2024) 177197.
78. [78] J. Fang, Y. Hu, Z. Hu, Comparative analysis of codon usage patterns in 16 chloroplast genomes of suborder Halimedineae, BMC Genomics, 25 (2024) 945.
79. [79] X. Zhang, G. Gao, Z. Gao, K. Gao, D. Liu, The contribution of biophysical and biochemical CO2 concentration mechanisms to the carbon fixation of the green macroalga Ulva prolifera, MLST, (2024) 1–12.
80. [80] Z. Skok, M. Durcik, D. G. Skledar, M. Barančoková, L. P. Mašič, T. Tomašič, A. Zega, D. Kikelj, N. Zidar, J. Ilaš, Discovery of new ATP-competitive inhibitors of human DNA topoisomerase IIα through screening of bacterial topoisomerase inhibitors, Bioorg. Chem., 102 (2020) 104049.
81. [81] S. Baikar, N. Malpathak, Secondary metabolites as DNA topoisomerase inhibitors: A new era towards designing of anticancer drugs, Pharmacogn. Rev., 4 (2010) 12–26.
82. [82] O. Kurt, F. Ozdal-Kurt, I. Tuglu, S. I. Deliloglu-Gurhan, M. Ozturk, “Neurotoxic effect of Caulerpa racemosa var. cylindracea by neurite inhibition on the neuroblastoma cell line” Russ. J. Mar. Biol., 5 (2009) 342–350.
83. [83] Y. Y. Chia, M. S. Kanthimathi, K. S. Khoo, J. Rajarajeswaran, H. M. Cheng, W. S. Yap, Antioxidant and cytotoxic activities of three species of tropical seaweeds, BMC Complement Altern. Med., 15 (2015)
84. [84] X. Xiao, M. Xu, C. Yang, Y. Yao, L. N. Liang, P. E. D. Chung, et al., Novel racemosin B derivatives as new therapeutic agents for aggressive breast cancer, Bioorg. Med. Chem., 26 (2018) 6096–6104.
85. [85] B. Tanna, B. Choudhary, A. Mishra, Metabolite profiling, antioxidant, scavenging and anti-proliferative activities of selected tropical green seaweeds reveal the nutraceutical potential of Caulerpa spp., Algal Res., 36 (2018) 96–105.
86. [86] H. K. Permatasari, S. Bulain, M. R. Azizah, F. Z. Muslim, V. P. A. Daud, F. Nurkolis, Anticancer Properties of Caulerpa racemosa: A Review Study, Nutr. Clín. Diet. Hosp., 42 (2022) 110-121
87. [87] M. D. Guiry, G. M. Guiry, AlgaeBase. World-wide electronic publication, University of Galway, 2025. https://www.algaebase.org, Accessed 10 September 2025.
88. [88] M. Verlaque, S. Ruitton, F. Mineur, C.-F. Boudouresque, CIESM Atlas of exotic macrophytes in the Mediterranean Sea, Rapp. Comm. int Mer. Médit., 38 (2007) 14.
89. [89] C.-F. Boudouresque, M. Verlaque, Biological pollution in the Mediterranean Sea: invasive versus introduced macrophytes, Mar. Pollut. Bull., 44 (2002) 32–38.
90. [90] K. Chakraborty, A. M. George, T. J. Mereeta, C. Bose, M. J. Jetlin, Classification of organic compounds with reference to natural products from seaweeds, in Course Manual: ICAR Winter School on Harnessing Recent Advances in High-Value Compound Development and Seaweed Biomass Utilization for Human Well-being: Propelling Atmanirbhar Swastha Bharat and Empowering Farmers, ICAR–Central Marine Fisheries Research Institute, Kochi, India 2024, pp. 56–69.
91. [91] S. Hosseinzadeh, M. Heydari, S. Afsharmanesh, A. Hosseini, The comparison of antioxidant power of two marine algae species with the skin of oak fruit (Quercus brantii), WJFMS, 7 (2015) 237–242.
92. [92] T. Lafarga, F. G. Acién-Fernández, M. Garcia-Vaquero, Bioactive peptides and carbohydrates from seaweed for food applications: natural occurrence, isolation, purification, and identification, Algal Res., 48 (2020) 101909.
93. [93] A. K. Mandal, S. Parida, A. K. Behera, S. P. Adhikary, A. A. Lukatkin, S. A. Lukatkin, M. Jena, Seaweed in the diet as a source of bioactive metabolites and a potential natural immunity booster: a comprehensive review, Pharmaceuticals, 18 (2025) 367.
94. [94] M. S. Muthuraman, S. Mani, U. Thangaraj, A. Sivasubramanian, In vitro cytotoxicity and molecular docking studies on Acanthophora spicifera, Der. Pharma. Chemica., 6 (2014) 411–417.
95. [95] B. Babu, S. Palanisamy, M. Vinosha, R. Anjali, P. Kumar, B. Pandi, N. M. Prabhu, Bioengineered gold nanoparticles from marine seaweed Acanthophora spicifera for pharmaceutical uses: antioxidant, antibacterial, and anticancer activities, Bioprocess Biosyst. Eng., 43 (2020) 2231–2242.
96. [96] N. Salamat, N. Derakhshesh, N. Shiry, S. J. Alavinia, Cytotoxic activities of Padina gymnospora and Acanthophora spicifera extracts against human breast cancer cell lines, Iran J. Fish. Sci., 21 (2022) 1527–1538.
97. [97] J. L. Nitiss, K. Kiianitsa, Y. Sun, K. C. Nitiss, N. Maizels, Topoisomerase Assays, Curr. Protoc., 1 (2021) e250.
98. [98] M. Senarisoy, P. Canturk, S. Zencir, Y. Baran, Z. Topcu, Gossypol interferes with both type I and type II topoisomerase activities without generating strand breaks, Cell Biochem. Biophys., 67 (2013) 1073–1083.
99. [99] N. Khaiwa, N. R. Maarouf, M. H. Darwish, D. W. M. Alhamad, A. Sebastian, et al., Camptothecin’s journey from discovery to WHO Essential Medicine: Fifty years of promise, Eur. J.. Med. Chem., 223 (2021) 113639.