Marine natural products have drawn a great deal of attention as a vital source of new drugs for the last five decades. However, marine organisms in the seas surrounding Turkey (the Black Sea, the Aegean Sea and the Mediterranean Sea) haven’t been yet extensively explored. In the present study, three marine organisms (Dysidea avara, Microcosmus sabatieri and Echinaster sepositus) were sampled from the Dardanelles (Turkish Straits System, Western Turkey) by scientific divers, transferred to the laboratory and then were extracted with 70% ethanol. The extracts were tested for their cytotoxic effect against K562, KMS-12PE, A549, and A375 cancer cell lines. The sponge extract elicited the most promising cytotoxic activity, thus it was further evaluated against H929, MCF-7, HeLa, and HCT116 cancer cells. Most of the designated cells showed a considerable sensitivity for the sponge extract particularly H929, K562, KMS-12PE and HeLa cells with IC50 less than 10 μg/mL. On the contrary, the other two extracts exhibited no cytotoxic activity on all cells at 100 μg/mL concentration. The sponge extract was tested for its capacity to induce apoptosis in cancer cells and to inhibit a panel of tyrosine kinases showing remarkable results. The outcome of this study represents a platform for discovery of new chemotherapeutic agents of marine natural origin.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Nasr H, Abdel-Aziz M, Radwan M, Shaaban M (2015) Bioactive secondary metabolites from terrestrial Streptomyces baarnensis MH4. Br J Pharma Res 5:72–81. https://doi.org/10.9734/BJPR/2015/14074
Zhang C, Liu Y (2015) Targeting cancer with sesterterpenoids: the new potential antitumor drugs. J Nat Med 69:255–266. https://doi.org/10.1007/s11418-015-0911-y
Radwan MO, Ismail MAH, El-Mekkawy S et al (2016) Synthesis and biological activity of new 18β-glycyrrhetinic acid derivatives. Arab J Chem 9:390–399. https://doi.org/10.1016/j.arabjc.2013.06.032
Aung T, Qu Z, Kortschak R, Adelson D (2017) Understanding the effectiveness of natural compound mixtures in Cancer through their molecular mode of action. Int J Mol Sci 18:656. https://doi.org/10.3390/ijms18030656
Ibrahim M, El-Alfy A, Ezel K et al (2017) Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space. Marine Drugs 15:248. https://doi.org/10.3390/md15080248
Pujiastuti DY, Ghoyatul Amin MN, Alamsjah MA, Hsu J-L (2019) Marine organisms as potential sources of bioactive peptides that inhibit the activity of angiotensin I-converting enzyme: a review. Molecules 24:2541. https://doi.org/10.3390/molecules24142541
Zhang H, Dong M, Chen J et al (2017) Bioactive secondary metabolites from the marine sponge genus Agelas. Marine Drugs 15:351. https://doi.org/10.3390/md15110351
Heydari H, Gozcelioglu B, Konulugil B (2019) Biodiversity and secondary metabolites of marine sponges from Turkey. Rec Nat Prod 13:367–378. https://doi.org/10.25135/rnp.118.18.07.340
Shinde P, Banerjee P, Mandhare A (2019) Marine natural products as source of new drugs: a patent review (2015–2018). Exp Opin Ther Patents 29:283–309. https://doi.org/10.1080/13543776.2019.1598972
Liang X, Luo D, Luesch H (2019) Advances in exploring the therapeutic potential of marine natural products. Pharmacol Res 147:104373. https://doi.org/10.1016/j.phrs.2019.104373
Newman D, Cragg G (2014) Marine-sourced anti-Cancer and Cancer pain control agents in clinical and late preclinical development. Marine Drugs 12:255–278. https://doi.org/10.3390/md12010255
Skropeta D, Pastro N, Zivanovic A (2011) Kinase inhibitors from marine sponges. Marine Drugs 9:2131–2154. https://doi.org/10.3390/md9102131
Chakraborty C, Hsu C-H, Wen Z-H, Lin C-S (2009) Anticancer drugs discovery and development from marine organisms. Curr Top Med Chem 9:1536–1545. https://doi.org/10.2174/156802609789909803
Cooper EL, Yao D (2012) Diving for drugs: tunicate anticancer compounds. Drug Discov Today 17:636–648. https://doi.org/10.1016/j.drudis.2012.02.006
Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Discov 8:69–85. https://doi.org/10.1038/nrd2487
Mehbub M, Lei J, Franco C, Zhang W (2014) Marine sponge derived natural products between 2001 and 2010: trends and opportunities for discovery of bioactives. Marine Drugs 12:4539–4577. https://doi.org/10.3390/md12084539
Takamatsu S (2018) Naturally occurring cell adhesion inhibitors. J Nat Med 72:817–835. https://doi.org/10.1007/s11418-018-1220-z
Anuradha V, Byju K, Emilda R, Anu G, Nair SM, Chandramohanakumar N, Peter KJP, Kumar TRG, Vasundhara G (2013) In silico biological activity of steroids from the marine sponge Axinella carteri. Med Chem Res 22:1142–1146. https://doi.org/10.1007/s00044-012-0119-6
Çelenk FG, Özkaya AB, Sukatar A (2016) Macroalgae of Izmir gulf: Dictyotaceae exhibit high in vitro anti-cancer activity independent from their antioxidant capabilities. Cytotechnology 68:2667–2676. https://doi.org/10.1007/s10616-016-9991-0
Dogan E, Demir O, Sertdemir M, et al (2018) Screening of the selected marine sponges from the coasts of Turkey for antimicrobial activity. Indian J Geo-Mar Sci
Özalp HB, Alparslan M (2016) Scleractinian diversity in the Dardanelles and Marmara Sea (Turkey): morphology, ecology and distributional patterns. Oceanol Hydrobiol Stud 45:259–285. https://doi.org/10.1515/ohs-2016-0023
Özalp HB, Caroselli E, Raimondi F, Goffredo S (2018) Skeletal growth, morphology and skeletal parameters of a temperate, solitary and zooxanthellate coral along a depth gradient in the Dardanelles (Turkey). Coral Reefs 37:633–646. https://doi.org/10.1007/s00338-018-1687-9
Altıntop M, Ciftci H, Radwan M et al (2017) Design, synthesis, and biological evaluation of novel 1,3,4-Thiadiazole derivatives as potential antitumor agents against chronic Myelogenous leukemia: striking effect of Nitrothiazole moiety. Molecules 23:59. https://doi.org/10.3390/molecules23010059
Dagenais GR, Leong DP, Rangarajan S et al (2019) Variations in common diseases, hospital admissions, and deaths in middle-aged adults in 21 countries from five continents (PURE): a prospective cohort study. Lancet. https://doi.org/10.1016/S0140-6736(19)32007-0
Sever B, Altıntop MD, Radwan MO, Özdemir A, Otsuka M, Fujita M, Ciftci HI (2019) Design, synthesis and biological evaluation of a new series of thiazolyl-pyrazolines as dual EGFR and HER2 inhibitors. Eur J Med Chem 182:111648. https://doi.org/10.1016/j.ejmech.2019.111648
Ali TFS, Ciftci HI, Radwan MO et al (2019) New SIRT2 inhibitors: Histidine-based bleomycin spin-off. Bioorg Med Chem. https://doi.org/10.1016/j.bmc.2019.03.003
Radwan MO, Ciftci HI, Ali TFS et al (2019) Antiproliferative S-Trityl-l-cysteine -derived compounds as SIRT2 inhibitors: repurposing and solubility enhancement. Molecules 24:3295. https://doi.org/10.3390/molecules24183295
Ciftci HI, Radwan MO, Ozturk SE et al (2019) Design, synthesis and biological evaluation of Pentacyclic Triterpene derivatives: optimization of anti-ABL kinase activity. Molecules 24:3535. https://doi.org/10.3390/molecules24193535
Shida W, Tateishi H, Tahara Y et al (2019) Antileukemic activity of twig components of Caucasian beech in Turkey. Molecules 24:3850. https://doi.org/10.3390/molecules24213850
Bayrak N, Yıldırım H, Yıldız M et al (2020) A novel series of chlorinated plastoquinone analogs: design, synthesis, and evaluation of anticancer activity. Chemical Biology & Drug Design cbdd.13651. https://doi.org/10.1111/cbdd.13651
Ciftci HI, Bayrak N, Yıldırım H et al (2019) Discovery and structure–activity relationship of plastoquinone analogs as anticancer agents against chronic myelogenous leukemia cells. Arch Pharm 352:1900170. https://doi.org/10.1002/ardp.201900170
Bayrak N, Yıldırım H, Yıldız M, Radwan MO, Otsuka M, Fujita M, Tuyun AF, Ciftci HI (2019) Design, synthesis, and biological activity of Plastoquinone analogs as a new class of anticancer agents. Bioorg Chem 92:103255. https://doi.org/10.1016/j.bioorg.2019.103255
Ciftci HI, Ozturk SE, Ali TFS, Radwan MO, Tateishi H, Koga R, Ocak Z, Can M, Otsuka M, Fujita M (2018) The first Pentacyclic Triterpenoid Gypsogenin derivative exhibiting anti-ABL1 kinase and anti-chronic Myelogenous leukemia activities. Biol Pharm Bull 41:570–574. https://doi.org/10.1248/bpb.b17-00902
Lee RH, Slate DL, Moretti R, Alvi KA, Crews P (1992) Marine sponge polyketide inhibitors of protein tyrosine kinase. Biochem Biophys Res Commun 184:765–772. https://doi.org/10.1016/0006-291X(92)90656-6
Yoo H-D, Leung D, Sanghara J et al (2003) Isoarenarol, a new protein kinase inhibitor from the marine sponge Dysidea arenaria. Pharm Biol 41:223–225. https://doi.org/10.1076/phbi.220.127.116.1179
Bilalis A, Pouliou E, Roussou M et al Increased expression of platelet derived growth factor receptor β on trephine biopsies correlates with advanced myeloma. J BUON 22:1032–1037
Ribatti D, Vacca A (2018) New insights in anti-angiogenesis in multiple myeloma. Int J Mol Sci 19:2031. https://doi.org/10.3390/ijms19072031
Wadleigh M, DeAngelo DJ, Griffin JD, Stone RM (2005) After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies. Blood 105:22–30. https://doi.org/10.1182/blood-2003-11-3896
Gars E, McGee CS, Bosse RC et al (2010) Acute myeloid leukemia cells depend on VEGF, PDGFR and SCF receptor signaling: leukemia regression with Pazopanib. Blood 116:1057–1057. https://doi.org/10.1182/blood.V116.21.1057.1057
Lu L, Zhao T-T, Liu T-B, Sun WX, Xu C, Li DD, Zhu HL (2016) Synthesis, molecular modeling and biological evaluation of 4-Alkoxyquinazoline derivatives as novel inhibitors of VEGFR2. Chem Pharm Bull 64:1570–1575. https://doi.org/10.1248/cpb.c16-00386
MCF7 cells were provided by the RIKEN BRC through the National Bio-Resource Project of the MEXT/AMED, Japan. We also would like to thank to K. E. BARIS, Umut DARYOL and İlker PAŞA for their strenuous support during the scientific dives and ecological surveys in situ.
We are grateful to the Screening Committee of Anticancer Drugs supported by a Grant-in-Aid for Scientific Research on Innovative Areas, Scientific Support Programs for Cancer Research (No. 221S0001), from The Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT), for assistance with the evaluation of compounds. This work was supported by a Grant for Joint Research Project with Science Farm Ltd. The study was also supported in part by a Grant-in-Aid for Challenging Exploratory Research to M.O. (24659048). We are grateful for the support from Izmir Katip Celebi University grants commision (project number: 2019-ÖNAP-SUÜF-0002)
Conflict of interest
All authors declare that there is no conflict of interest in this article.
This article does not contain any studies with human participants or animals performed by any of the authors.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Ciftci, H.I., Can, M., Ellakwa, D.E. et al. Anticancer activity of Turkish marine extracts: a purple sponge extract induces apoptosis with multitarget kinase inhibition activity. Invest New Drugs 38, 1326–1333 (2020). https://doi.org/10.1007/s10637-020-00911-8
- Marine products
- Tyrosine kinase inhibitors