Marine anticancer drugs and their relevant targets: a treasure from the ocean

Abstract

Marine organisms comprising animals and plants are wealthiest sources of bioactive compounds possessing various pharmacological properties specifically: free radical scavenging, antitumor, antimicrobial, analgesic, neuroprotective and immunomodulatory. Marine drugs provide an alternative source to meet the demand of effective, safe and low-cost drugs that are rising with the continuously growing world population. Cancer is one of the leading reasons of mortality in western nations in contrast to communicable diseases of developing nations. In spite of outstanding developments in cancer therapy in past three decades, there is still an insistent necessity for innovative drugs in the area of cancer biology, especially in the unexplored area of marine anticancer compounds. However, recent technological innovations in structure revelation, synthetic creation of new compounds and biological assays have made possible the isolation and clinical assessment of innumerable unique anticancer compounds from marine environment. This review provides an insight into the anticancer research so far conducted in the area of the marine natural products/synthetic derivatives, their possible molecular targets and the current challenges in the drug development.

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

References

  1. 1.

    Suleria HAR, Gobe G, Masci P, Osborne SA. Marine bioactive compounds and health promoting perspectives; innovation pathways for drug discovery. Trends Food Sci Technol. 2016;50:44–55.

    Article  CAS  Google Scholar 

  2. 2.

    Suleria HAR, Osborne S, Masci P, Gobe G. Marine-based nutraceuticals: an innovative trend in the food and supplement industries. Mar Drugs. 2015;13:6336–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Kathiresan K, Duraisamy A. Current issues of marine microbiology. ENVIS is Envoirnmental information system. 2005;4:3–5.

    Google Scholar 

  4. 4.

    Jimeno J, Faircloth G, Sousa-Faro JMF, Scheuer P, Rinehart K. New marine derived anticancer therapeutics ─ a journey from the sea to clinical trials. Mar Drugs. 2004;2:14–29.

    Article  CAS  PubMed Central  Google Scholar 

  5. 5.

    Lindequist U. Marine derived pharmaceuticals - challenges and opportunities. Biomol Ther. 2016;24:561–71.

    Article  CAS  Google Scholar 

  6. 6.

    Leal MC, Madeira C, Brandão CA, Puga J, Calado R. Bioprospecting of marine invertebrates for new natural products — a chemical and zoogeographical perspective. Molecules. 2012;17:9842–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Malve H. Exploring the ocean for new drug developments: marine pharmacology. J Pharm Bioallied Sci. 2016;8:83–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Dyshlovoy SA, Honecker F. Marine compounds and cancer: where do we stand? Mar Drugs. 2015;13:5657–65.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Bergmann W, Feeney RJ. Contributions to the study of marine products. XXXII. The nucleosides of sponges. I. 1. J Org Chem. 1951;16:981–7.

    Article  CAS  Google Scholar 

  10. 10.

    Bergmann W, Stempien MF. Contributions to the study of marine products. XLIII. The nucleosides of sponges. V. the synthesis of spongosine 1. J Org Chem. 1957;22:1575–7.

    Article  CAS  Google Scholar 

  11. 11.

    Bergmann W, Burke DC. Contributions to the study of marine products. XL. The nucleosides of sponges.1 IV. Spongosine 2. J Org Chem. 1956;21:226–8.

    Article  CAS  Google Scholar 

  12. 12.

    Suleria HAR, Masci P, Gobe G, Osborne S. Current and potential uses of bioactive molecules from marine processing waste. J Sci Food Agric. 2016;96:1064–7.

    Article  CAS  PubMed  Google Scholar 

  13. 13.

    Kong D-X, Jiang Y-Y, Zhang H-Y. Marine natural products as sources of novel scaffolds: achievement and concern. Drug Discov Today. 2010;15:884–6.

    Article  PubMed  Google Scholar 

  14. 14.

    Molinski TF, Dalisay DS, Lievens SL, Saludes JP. Drug development from marine natural products. Nat Rev Drug Discov. 2009;8:69–85.

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Ruiz-Torres V, Encinar JA, Herranz-López M, Pérez-Sánchez A, Galiano V, Barrajón-Catalán E, et al. An updated review on marine anticancer compounds: the use of virtual screening for the discovery of small-molecule cancer drugs. Molecules. 2017;22:E1037.

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Munro MH, Blunt JW, Dumdei EJ, Hickford SJ, Lill RE, Li S, et al. The discovery and development of marine compounds with pharmaceutical potential. J Biotechnol. 1999;70(1–3):15–25.

    Article  CAS  PubMed  Google Scholar 

  17. 17.

    Muñoz-Alonso MJ, González-Santiago L, Zarich N, Martínez T, Alvarez E, Rojas JM, et al. Plitidepsin has a dual effect inhibiting cell cycle and inducing apoptosis via Rac1/c-Jun NH2-terminal kinase activation in human melanoma cells. J Pharmacol Exp Ther. 2008;324:1093–101.

    Article  CAS  PubMed  Google Scholar 

  18. 18.

    Landowne RA, Bergmann W. Contributions to the study of marine products. L. Phospholipids of sponges1,2. J Org Chem. 1961;26:1257–61.

    Article  CAS  Google Scholar 

  19. 19.

    Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996;87:1710–7.

    CAS  PubMed  Google Scholar 

  20. 20.

    Stentoft J. The toxicity of cytarabine. Drug Saf. 1990;5:7–27.

    Article  CAS  PubMed  Google Scholar 

  21. 21.

    Mayer AMS, Glaser KB, Cuevas C, Jacobs RS, Kem W, Little RD, et al. The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci. 2010;31:255–65.

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Gajdos C, Elias A. Trabectedin: safety and efficacy in the treatment of advanced sarcoma. Clin Med Insights Oncol. 2011;5:35–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Shetty N, Gupta S. Eribulin drug review. South Asian J Cancer. 2014;3:57–9.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Smith JA, Wilson L, Azarenko O, Zhu X, Lewis BM, Littlefield BA, et al. Eribulin binds at microtubule ends to a single site on tubulin to suppress dynamic instability. Biochemistry. 2010;49:1331–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Doronina SO, Mendelsohn BA, Bovee TD, Cerveny CG, Alley SC, Meyer DL, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem. 2006;17:114–24.

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Ansell SM. Brentuximab vedotin: delivering an antimitotic drug to activated lymphoma cells. Expert Opin Investig Drugs. 2011;20:99–105.

    Article  CAS  PubMed  Google Scholar 

  27. 27.

    Luesch H, Moore RE, Paul VJ, Mooberry SL, Corbett TH. Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. J Nat Prod. 2001;64:907–10.

    Article  CAS  PubMed  Google Scholar 

  28. 28.

    Sutherland MSK, Sanderson RJ, Gordon KA, Andreyka J, Cerveny CG, Yu C, et al. Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptide-linked anti-CD30-auristatin conjugates. J Biol Chem. 2006;281:10540–7.

    Article  CAS  PubMed  Google Scholar 

  29. 29.

    Fromm JR, McEarchern JA, Kennedy D, Thomas A, Shustov AR, Gopal AK. Clinical binding properties, internalization kinetics, and clinicopathologic activity of brentuximab vedotin: an antibody-drug conjugate for CD30-positive lymphoid neoplasms. Clin Lymphoma Myeloma Leuk. 2012;12:280–3.

    Article  CAS  PubMed  Google Scholar 

  30. 30.

    McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3:69–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Staats PS, Yearwood T, Charapata SG, Presley RW, Wallace MS, Byas-Smith M, et al. Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial. JAMA. 2004;291:63–70.

    Article  CAS  PubMed  Google Scholar 

  32. 32.

    De NP, Tirri T, Mameli S, Papa A. Intrathecal ziconotide for cancer pain relief: when, how and why. J Anesth Clin Res. 2012;3:227.

    Google Scholar 

  33. 33.

    Cheung RCF, Ng TB, Wong JH. Marine peptides: bioactivities and applications. Mar Drugs. 2015;13:4006–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 34.

    Muñoz-Alonso MJ, González-Santiago L, Martínez T, Losada A, Galmarini CM, Muñoz A. The mechanism of action of plitidepsin. Curr Opin Investig Drugs. 2009;10:536–42.

    PubMed  Google Scholar 

  35. 35.

    Krege S, Rexer H, vom Dorp F, de Geeter P, Klotz T, Retz M, et al. Prospective randomized double-blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO-AB 31/05). BJU Int. 2014;113:429–36.

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Akashi Y, Oda T, Ohara Y, Miyamoto R, Kurokawa T, Hashimoto S, et al. Anticancer effects of gemcitabine are enhanced by co-administered iRGD peptide in murine pancreatic cancer models that overexpressed neuropilin-1. Br J Cancer. 2014;110:1481–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Kuo W-T, Huang J-Y, Chen M-H, Chen C-Y, Shyong Y-J, Yen K-C, et al. Development of gelatin nanoparticles conjugated with phytohemagglutinin erythroagglutinating loaded with gemcitabine for inducing apoptosis in non-small cell lung cancer cells. J Mater Chem B. 2016;4:2444–54.

    Article  CAS  Google Scholar 

  38. 38.

    Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin Oncol. 1995;22:3–10.

    CAS  PubMed  Google Scholar 

  39. 39.

    Natsume T, Watanabe J, Ogawa K, Yasumura K, Kobayashi M. Tumor-specific antivascular effect of TZT-1027 (Soblidotin) elucidated by magnetic resonance imaging and confocal laser scanning microscopy. Cancer Sci. 2007;98:598–604.

    Article  CAS  PubMed  Google Scholar 

  40. 40.

    Hamann MT, Otto CS, Scheuer PJ, Dunbar DC. Bioactive peptides from a marine mollusk Elysia rufescens and its algal diet Bryopsis sp. (1). J Org Chem. 1996;61:6594–600.

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Ling Y-H, Aracil M, Zou Y, Yuan Z, Lu B, Jimeno J, et al. PM02734 (elisidepsin) induces caspase-independent cell death associated with features of autophagy, inhibition of the Akt/mTOR signaling pathway, and activation of death-associated protein kinase. Clin Cancer Res. 2011;17:5353–66.

    Article  CAS  PubMed  Google Scholar 

  42. 42.

    Ott PA, Pavlick AC, Johnson DB, Hart LL, Infante JR, Luke JJ, et al. A phase II study of glembatumumab vedotin (GV), an antibody-drug conjugate (ADC) targeting gpNMB, in advanced melanoma. J Clin Oncol. 2017;35:109.

    Article  Google Scholar 

  43. 43.

    Keir CH, Vahdat LT. The use of an antibody drug conjugate, glembatumumab vedotin (CDX-011), for the treatment of breast cancer. Expert Opin Biol Ther. 2012;12:259–63.

    Article  CAS  PubMed  Google Scholar 

  44. 44.

    Caplan S, Zheng B, Dawson-Scully K, White C, West L. Pseudopterosin a: protection of synaptic function and potential as a neuromodulatory agent. Mar Drugs. 2016;14:55.

    Article  CAS  PubMed Central  Google Scholar 

  45. 45.

    Sperlich J, Kerr R, Teusch N. The marine natural product Pseudopterosin blocks cytokine release of triple-negative breast cancer and monocytic leukemia cells by inhibiting NF-κB signaling. Mar Drugs. 2017;15:E262.

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Fontana A, Cavaliere P, Wahidulla S, Naik CG, Cimino G. A new antitumor isoquinoline alkaloid from the marine nudibranch Jorunna funebris. Tetrahedron. 2000;56:7305–8.

    Article  CAS  Google Scholar 

  47. 47.

    Oku N, Matsunaga S, van Soest RWM, Fusetani N. Renieramycin J, a highly cytotoxic tetrahydroisoquinoline alkaloid, from a marine sponge Neopetrosia sp. J Nat Prod. 2003;66:1136–9.

    Article  CAS  PubMed  Google Scholar 

  48. 48.

    Petek BJ, Jones RL. PM00104 (Zalypsis®): a marine derived alkylating agent. Molecules. 2014;19:12328–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Longley RE, Caddigan D, Harmody D, Gunasekera M, Gunasekera SP. Discodermolide--a new, marine-derived immunosuppressive compound. II. In-vivo studies. Transplantation. 1991;52:656–61.

    Article  CAS  PubMed  Google Scholar 

  50. 50.

    Longley RE, Caddigan D, Harmody D, Gunasekera M, Gunasekera SP. Discodermolide--a new, marine-derived immunosuppressive compound. I. In-vitro studies. Transplantation. 1991;52:650–6.

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    ter Haar E, Rosenkranz HS, Hamel E, Day BW. Computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents. Bioorganic Med Chem. 1996;4:1659–71.

    Article  Google Scholar 

  52. 52.

    Honore S, Kamath K, Braguer D, Wilson L, Briand C, Jordan MA. Suppression of microtubule dynamics by discodermolide by a novel mechanism is associated with mitotic arrest and inhibition of tumor cell proliferation. Mol Cancer Ther. 2003;2:1303–11.

    CAS  PubMed  Google Scholar 

  53. 53.

    Pettit GR, Herald CL, Doubek DL, Herald DL, Arnold E, Clardy J. Isolation and structure of bryostatin 1. J Am Chem Soc. 1982;104:6846–8.

    Article  CAS  Google Scholar 

  54. 54.

    Trenn G, Pettit GR, Takayama H, Hu-Li J, Sitkovsky MV. Immunomodulating properties of a novel series of protein kinase C activators. The bryostatins. J Immunol. 1988;140:433–9.

    CAS  PubMed  Google Scholar 

  55. 55.

    Kobayashi M, Natsume T, Tamaoki S, Watanabe J, Asano H, Mikami T, et al. Antitumor activity of TZT-1027, a novel dolastatin 10 derivative. Jpn J Cancer Res. 1997;88:316–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Hornung RL, Pearson JW, Beckwith M, Longo DL. Preclinical evaluation of bryostatin as an anticancer agent against several murine tumor cell lines: in-vitro versus in-vivo activity. Cancer Res. 1992;52:101–7.

    CAS  PubMed  Google Scholar 

  57. 57.

    Advani RH, Lebovic D, Chen A, Brunvand M, Goy A, Chang JE, et al. Phase I study of the anti-CD22 antibody-drug conjugate Pinatuzumab Vedotin with/without rituximab in patients with relapsed/refractory B-cell non-hodgkin lymphoma. Clin Cancer Res. 2017;23:1167–76.

    Article  CAS  PubMed  Google Scholar 

  58. 58.

    Förster Y, Meye A, Albrecht S, Schwenzer B. Tissue factor and tumor: clinical and laboratory aspects. Clin Chim Acta. 2006;364:12–21.

    Article  CAS  PubMed  Google Scholar 

  59. 59.

    Cocco E, Varughese J, Buza N, Bellone S, Glasgow M, Bellone M, et al. Expression of tissue factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix: implications for immunotherapy with hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor. BMC Cancer. 2011;11:263.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Coleman JE, Dilip de Silva E, Kong F, Andersen RJ, Allen TM. Cytotoxic peptides from the marine sponge Cymbastela sp. Tetrahedron. 1995;51:10653–62.

    Article  CAS  Google Scholar 

  61. 61.

    Talpir R, Benayahu Y, Kashman Y, Pannell L, Schleyer M. Hemiasterlin and geodiamolide TA; two new cytotoxic peptides from the marine sponge Hemiasterella minor (Kirkpatrick). Tetrahedron Lett. 1994;35:4453–6.

    Article  CAS  Google Scholar 

  62. 62.

    Gamble WR, Durso NA, Fuller RW, Westergaard CK, Johnson TR, Sackett DL, et al. Cytotoxic and tubulin-interactive hemiasterlins from Auletta sp. and Siphonochalina spp. sponges. Bioorganic Med Chem. 1999;7:1611–5.

    Article  CAS  Google Scholar 

  63. 63.

    Anderson HJ, Coleman JE, Andersen RJ, Roberge M. Cytotoxic peptides hemiasterlin, hemiasterlin a and hemiasterlin B induce mitotic arrest and abnormal spindle formation. Cancer Chemother Pharmacol. 1997;39:223–6.

    Article  CAS  PubMed  Google Scholar 

  64. 64.

    Quinoa E, Adamczeski M, Crews P, Bakus GJ. Bengamides, heterocyclic anthelmintics from a Jaspidae marine sponge. J Org Chem. 1986;51:4494–7.

    Article  CAS  Google Scholar 

  65. 65.

    Dumez H, Gall H, Capdeville R, Dutreix C, van Oosterom AT, Giaccone G. A phase I and pharmacokinetic study of LAF389 administered to patients with advanced cancer. Anti-Cancer Drugs. 2007;18:219–25.

    Article  CAS  PubMed  Google Scholar 

  66. 66.

    Towbin H, Bair KW, DeCaprio JA, Eck MJ, Kim S, Kinder FR, et al. Proteomics-based target identification: bengamides as a new class of methionine aminopeptidase inhibitors. J Biol Chem. 2003;278:52964–71.

    Article  CAS  PubMed  Google Scholar 

  67. 67.

    Martínez-Díez M, Guillén-Navarro MJ, Pera B, Bouchet BP, Martínez-Leal JF, Barasoain I, et al. PM060184, a new tubulin binding agent with potent antitumor activity including P-glycoprotein over-expressing tumors. Biochem Pharmacol. 2014;88:291–302.

    Article  CAS  PubMed  Google Scholar 

  68. 68.

    Zovko A, Viktorsson K, Lewensohn R, Kološa K, Filipič M, Xing H, et al. APS8, a polymeric alkylpyridinium salt blocks α7 nAChR and induces apoptosis in non-small cell lung carcinoma. Mar Drugs. 2013;11:2574–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Li H-H, Su J-H, Chiu C-C, Lin J-J, Yang Z-Y, Hwang W-I, et al. Proteomic investigation of the sinulariolide-treated melanoma cells A375: effects on the cell apoptosis through mitochondrial-related pathway and activation of caspase cascade. Mar Drugs. 2013;11:2625–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Su J-H, Chen Y-C, El-Shazly M, Du Y-C, Su C-W, Tsao C-W, et al. Towards the small and the beautiful: a small dibromotyrosine derivative from Pseudoceratina sp. sponge exhibits potent apoptotic effect through targeting IKK/NFκB signaling pathway. Mar Drugs. 2013;11:3168–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Esmaeelian B, Benkendorff K, Johnston MR, Abbott CA. Purified brominated indole derivatives from Dicathais orbita induce apoptosis and cell cycle arrest in colorectal cancer cell lines. Mar Drugs. 2013;11:3802–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Hamilton G. Cytotoxic effects of fascaplysin against small cell lung cancer cell lines. Mar Drugs. 2014;12:1377–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Akl MR, Ayoub NM, Ebrahim HY, Mohyeldin MM, Orabi KY, Foudah AI, et al. Araguspongine C induces autophagic death in breast cancer cells through suppression of c-Met and HER2 receptor tyrosine kinase signaling. Marine Drugs. 2015;13:288–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74.

    Aminin DL, Menchinskaya ES, Pisliagin EA, Silchenko AS, Avilov SA, Kalinin VI. Anticancer activity of sea cucumber triterpene glycosides. Mar Drugs. 2015;13:1202–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Walsh CJ, Luer CA, Yordy JE, Cantu T, Miedema J, Leggett SR, et al. Epigonal conditioned media from bonnethead shark, Sphyrna tiburo, induces apoptosis in a T-cell leukemia cell line, Jurkat E6-1. Mar Drugs. 2013;11:3224–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Pereira DM, Correia-da-Silva G, Valentão P, Teixeira N, Andrade PB. Palmitic acid and ergosta-7,22-dien-3-ol contribute to the apoptotic effect and cell cycle arrest of an extract from Marthasterias glacialis L. in neuroblastoma cells. Mar Drugs. 2013;12:54–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Teta R, Irollo E, Della Sala G, Pirozzi G, Mangoni A, Costantino V. Smenamides a and B, chlorinated peptide/polyketide hybrids containing a dolapyrrolidinone unit from the Caribbean sponge Smenospongia aurea. Evaluation of their role as leads in antitumor drug research. Mar Drugs. 2013;11:4451–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Huang X-C, Xiao X, Zhang Y-K, Talele TT, Salim AA, Chen Z-S, et al. Lamellarin O, a pyrrole alkaloid from an Australian marine sponge, Ianthella sp., reverses BCRP mediated drug resistance in cancer cells. Mar Drugs. 2014;12:3818–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Abraham I, Jain S, Wu C-P, Khanfar MA, Kuang Y, Dai C-L, et al. Marine sponge-derived sipholane triterpenoids reverse P-glycoprotein (ABCB1)-mediated multidrug resistance in cancer cells. Biochem Pharmacol. 2010;80:1497–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Fiorini L, Tribalat M-A, Sauvard L, Cazareth J, Lalli E, Broutin I, et al. Natural paniceins from mediterranean sponge inhibit the multidrug resistance activity of patched and increase chemotherapy efficiency on melanoma cells. Oncotarget. 2015;6:22282–97.

    Article  PubMed  PubMed Central  Google Scholar 

  81. 81.

    Canals A, Arribas-Bosacoma R, Albericio F, Álvarez M, Aymamí J, Coll M. Intercalative DNA binding of the marine anticancer drug variolin B. Sci Rep. 2017;7:39680.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 82.

    Choi MY, Cardenas JM, Lu D, Yu J, Stout EP, Wu RP, et al. Agelastatin A (AgA), a marine sponge derived alkaloid, inhibits Wnt/Beta-catenin signaling and selectively induces apoptosis in chronic lymphocytic leukemia independently of p53. Blood. 2011;118:1786.

    Google Scholar 

  83. 83.

    Catley L, Weisberg E, Tai Y-T, Atadja P, Remiszewski S, Hideshima T, et al. NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma. Blood. 2003;102:2615–22.

    Article  CAS  PubMed  Google Scholar 

  84. 84.

    Potts BC, Albitar MX, Anderson KC, Baritaki S, Berkers C, Bonavida B, et al. Marizomib, a proteasome inhibitor for all seasons: preclinical profile and a framework for clinical trials. Curr Cancer Drug Targets. 2011;11:254–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Hughes CC, MacMillan JB, Gaudêncio SP, Jensen PR, Fenical W. The ammosamides: structures of cell cycle modulators from a marine-derived Streptomyces species. Angew Chem Int Ed Engl. 2009;48:725–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Sagar S, Esau L, Holtermann K, Hikmawan T, Zhang G, Stingl U, et al. Induction of apoptosis in cancer cell lines by the Red Sea brine pool bacterial extracts. BMC Complement Altern Med. 2013;13:344.

    Article  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Sagar S, Esau L, Hikmawan T, Antunes A, Holtermann K, Stingl U, et al. Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea. BMC Complement Altern Med. 2013;13:29.

    Article  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Trzoss L, Fukuda T, Costa-Lotufo LV, Jimenez P, La Clair JJ, Fenical W. Seriniquinone, a selective anticancer agent, induces cell death by autophagocytosis, targeting the cancer-protective protein dermcidin. Proc Natl Acad Sci U S A. 2014;111:14687–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Alvarez-Mico X, Jensen PR, Fenical W, Hughes CC. Chlorizidine, a cytotoxic 5H-pyrrolo[2,1-a]isoindol-5-one-containing alkaloid from a marine Streptomyces sp. Org Lett. 2013;15:988–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Erba E, Bergamaschi D, Ronzoni S, Faretta M, Taverna S, Bonfanti M, et al. Mode of action of thiocoraline, a natural marine compound with anti-tumour activity. Br J Cancer. 1999;80:971–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Singh AV, Bandi M, Raje N, Richardson P, Palladino MA, Chauhan D, et al. A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells. Blood. 2011;117:5692–700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. 92.

    Zhang J, Tao L, Liang Y, Chen L, Mi Y, Zheng L, et al. Anthracenedione derivatives as anticancer agents isolated from secondary metabolites of the mangrove endophytic fungi. Mar Drugs. 2010;8:1469–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. 93.

    Oda T, Namikoshi M, Akano K, Kobayashi H, Honma Y, Kasahara T. Verrucarin a inhibition of MAP kinase activation in a PMA-stimulated promyelocytic leukemia cell line. Mar Drugs. 2005;3:64–73.

    Article  CAS  PubMed Central  Google Scholar 

  94. 94.

    Gamal-Eldeen AM, Abdel-Lateff A, Okino T. Modulation of carcinogen metabolizing enzymes by chromanone a; a new chromone derivative from algicolous marine fungus Penicillium sp. Environ Toxicol Pharmacol. 2009;28:317–22.

    Article  CAS  PubMed  Google Scholar 

  95. 95.

    Wijesekara I, Zhang C, Van Ta Q, Vo T-S, Li Y-X, Kim S-K. Physcion from marine-derived fungus Microsporum sp. induces apoptosis in human cervical carcinoma HeLa cells. Microbiol Res. 2014;169:255–61.

    Article  CAS  PubMed  Google Scholar 

  96. 96.

    Li Y-X, Himaya SWA, Dewapriya P, Zhang C, Kim S-K. Fumigaclavine C from a marine-derived fungus Aspergillus fumigatus induces apoptosis in MCF-7 breast cancer cells. Mar Drugs. 2013;11:5063–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Chen J, Wang C, Lan W, Huang C, Lin M, Wang Z, et al. Gliotoxin inhibits proliferation and induces apoptosis in colorectal cancer cells. Mar Drugs. 2015;13:6259–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Stevenson CS, Capper EA, Roshak AK, Marquez B, Eichman C, Jackson JR, et al. The identification and characterization of the marine natural product scytonemin as a novel antiproliferative pharmacophore. J Pharmacol Exp Ther. 2002;303:858–66.

    Article  CAS  PubMed  Google Scholar 

  99. 99.

    Taori K, Paul VJ, Luesch H. Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp. J Am Chem Soc. 2008;130:1806–7.

    Article  CAS  PubMed  Google Scholar 

  100. 100.

    Moore RE. Cyclic peptides and depsipeptides from cyanobacteria: a review. J Ind Microbiol. 1996;16:134–43.

    Article  CAS  PubMed  Google Scholar 

  101. 101.

    Fischel JL, Lemee R, Formento P, Caldani C, Moll JL, Pesando D, et al. Cell growth inhibitory effects of caulerpenyne, a sesquiterpenoid from the marine algae Caulerpa taxifolia. Anticancer Res. 1995;15:2155–60.

    CAS  PubMed  Google Scholar 

  102. 102.

    Magarvey NA, Beck ZQ, Golakoti T, Ding Y, Huber U, Hemscheidt TK, et al. Biosynthetic characterization and chemoenzymatic assembly of the cryptophycins. Potent anticancer agents from cyanobionts. ACS Chem Biol. 2006;1:766–79.

    Article  CAS  PubMed  Google Scholar 

  103. 103.

    Atashrazm F, Lowenthal RM, Woods GM, Holloway AF, Dickinson JL. Fucoidan and cancer: a multifunctional molecule with anti-tumor potential. Mar Drugs. 2015;13:2327–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Yende SR, Harle UN, Chaugule BB. Therapeutic potential and health benefits of Sargassum species. Pharmacogn Rev. 2014;8:1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. 105.

    Yang L, Wang P, Wang H, Li Q, Teng H, Liu Z, et al. Fucoidan derived from Undaria pinnatifida induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the ROS-mediated mitochondrial pathway. Mar Drugs. 2013;11:1961–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    Boo H-J, Hong J-Y, Kim S-C, Kang J-I, Kim M-K, Kim E-J, et al. The anticancer effect of fucoidan in PC-3 prostate cancer cells. Mar Drugs. 2013;11:2982–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. 107.

    Shi D, Guo S, Fan X. A new ketosteroid from red alga Acanthophora spicifera. Chin J Ocean Limnol. 2011;29:674–8.

    Article  CAS  Google Scholar 

  108. 108.

    Verdier-Pinard P, Lai JY, Yoo HD, Yu J, Marquez B, Nagle DG, et al. Structure-activity analysis of the interaction of curacin a, the potent colchicine site antimitotic agent, with tubulin and effects of analogs on the growth of MCF-7 breast cancer cells. Mol Pharmacol. 1998;53:62–76.

    Article  CAS  PubMed  Google Scholar 

  109. 109.

    Kuda T, Yano T, Matsuda N, Nishizawa M. Inhibitory effects of laminaran and low molecular alginate against the putrefactive compounds produced by intestinal microflora in-vitro and in rats. Food Chem. 2005;91:745–9.

    Article  CAS  Google Scholar 

  110. 110.

    Mei C, Zhou S, Zhu L, Ming J, Zeng F, Xu R. Antitumor effects of Laminaria extract fucoxanthin on lung cancer. Mar Drugs. 2017;15:39.

    Article  CAS  PubMed Central  Google Scholar 

  111. 111.

    Wu N, Luo J, Jiang B, Wang L, Wang S, Wang C, et al. Marine bromophenol bis (2,3-Dibromo-4,5-dihydroxy-phenyl)-methane inhibits the proliferation, migration, and invasion of hepatocellular carcinoma cells via modulating β1-integrin/FAK signaling. Mar Drugs. 2015;13:1010–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Xu Y, Kersten RD, Nam S-J, Lu L, Al-Suwailem AM, Zheng H, et al. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents. J Am Chem Soc. 2012;134:8625–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Park H, Tuan N, Oh J, Son Y, Hamann M, Stone R, et al. Sesterterpenoid and steroid metabolites from a deep-water Alaska sponge inhibit Wnt/β-catenin signaling in colon cancer cells. Mar Drugs. 2018;16:297.

    Article  CAS  PubMed Central  Google Scholar 

  114. 114.

    Park S, Yun E, Hwang I, Yoon S, Kim D-E, Kim J, et al. Ilimaquinone and ethylsmenoquinone, marine sponge metabolites, suppress the proliferation of multiple myeloma cells by down-regulating the level of β-catenin. Mar Drugs. 2014;12:3231–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 115.

    Sithranga Boopathy N, Kandasamy K, Subramanian M, You-Jin J. Effect of mangrove tea extract from Ceriops decandra (Griff.) Ding Hou. On salivary bacterial flora of DMBA induced hamster buccal pouch carcinoma. Indian J Microbiol. 2011;51:338–44.

    Article  PubMed  PubMed Central  Google Scholar 

  116. 116.

    Firdaus M, Prihanto AA, Nurdiani R. Antioxidant and cytotoxic activity of Acanthus ilicifolius flower. Asian Pac J Trop Biomed. 2013;3:17–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Hameed E. Phytochemical studies and evaluation of antioxidant, anticancer and antimicrobial properties of Conocarpus erectus L. growing in Taif, Saudi Arabia. European J Med Plants. 2012;2:93–112.

    Article  Google Scholar 

  118. 118.

    Thatoi H, Samantaray D, Das SK. The genus Avicennia, a pioneer group of dominant mangrove plant species with potential medicinal values: a review. Front Life Sci. 2016;9:267–91.

    Article  CAS  Google Scholar 

  119. 119.

    Jaikumar K, Md. Sheik NM, Anand D, Saravanan P. anticancer activity of Calophyllum inophyllum L., ethanolic leaf extract in MCF human breast cell lines. Int J Pharm Sci Res 2016;7:3330–3335.

  120. 120.

    Masuda T, Yonemori S, Oyama Y, Takeda Y, Tanaka T, Andoh T, et al. Evaluation of the antioxidant activity of environmental plants: activity of the leaf extracts from Seashore plants. J Agric Food Chem. 1999;47:1749–54.

    Article  CAS  PubMed  Google Scholar 

  121. 121.

    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  PubMed  Google Scholar 

  122. 122.

    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

    Article  CAS  PubMed  Google Scholar 

  123. 123.

    Fouad YA, Aanei C. Revisiting the hallmarks of cancer. Am J Cancer Res. 2017;7:1016–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer. 2004;4:253–65.

    Article  CAS  PubMed  Google Scholar 

  125. 125.

    Garg AD, Nowis D, Golab J, Vandenabeele P, Krysko DV, Agostinis P. Immunogenic cell death, DAMPs and anticancer therapeutics: an emerging amalgamation. Biochim Biophys Acta. 2010;1805:53–71.

    CAS  PubMed  Google Scholar 

  126. 126.

    Fulda S, Pervaiz S. Apoptosis signaling in cancer stem cells. Int J Biochem Cell Biol. 2010;42:31–8.

    Article  CAS  PubMed  Google Scholar 

  127. 127.

    Oliver L, Vallette FM. The role of caspases in cell death and differentiation. Drug Resist Updat. 2005;8:163–70.

    Article  CAS  PubMed  Google Scholar 

  128. 128.

    Kroemer G. Mitochondrial control of apoptosis: an introduction. Biochem Biophys Res Commun. 2003;304:433–5.

    Article  CAS  PubMed  Google Scholar 

  129. 129.

    Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35:495–516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. 130.

    Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2:647–56.

    Article  CAS  PubMed  Google Scholar 

  131. 131.

    Pyo JO, Nah J, Jung YK. Molecules and their functions in autophagy. Exp Mol Med. 2012;44:73–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Cheetham GM. Novel protein kinases and molecular mechanisms of autoinhibition. Curr Opin Struct Biol. 2004;14:700–5.

    Article  CAS  PubMed  Google Scholar 

  133. 133.

    Skropeta D, Pastro N, Zivanovic A. Kinase inhibitors from marine sponges. Mar Drugs. 2011;9:2131–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Sharma PS, Sharma R, Tyagi R. Inhibitors of cyclin dependent kinases: useful targets for cancer treatment. Curr Cancer Drug Targets. 2008;8:53–75.

    Article  CAS  PubMed  Google Scholar 

  135. 135.

    Morgan D, Morgan DO. The cell cycle: principles of control: OUP/New Science Press; 2007.

  136. 136.

    Levitzki A, Mishani E. Tyrphostins and other tyrosine kinase inhibitors. Annu Rev Biochem. 2006;75:93–109.

    Article  CAS  PubMed  Google Scholar 

  137. 137.

    Carpenter G, Cohen S. Epidermal growth factor. Annu Rev Biochem. 1979;48:193–216.

    Article  CAS  PubMed  Google Scholar 

  138. 138.

    Nakao Y, Fusetani N. Enzyme inhibitors from marine invertebrates. J Nat Prod. 2007;70:689–710.

    Article  CAS  PubMed  Google Scholar 

  139. 139.

    Pearson G, Robinson F, Beers Gibson T, Xu BE, Karandikar M, Berman K, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001;22:153–83.

    CAS  PubMed  Google Scholar 

  140. 140.

    Brown MD, Sacks DB. Protein scaffolds in MAP kinase signalling. Cell Signal. 2009;21:462–9.

    Article  CAS  PubMed  Google Scholar 

  141. 141.

    Kannan-Thulasiraman P, Katsoulidis E, Tallman MS, Arthur JS, Platanias LC. Activation of the mitogen- and stress-activated kinase 1 by arsenic trioxide. J Biol Chem. 2006;281:22446–52.

    Article  CAS  PubMed  Google Scholar 

  142. 142.

    Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vascular development. Nature. 2005;438:937–45.

    Article  CAS  PubMed  Google Scholar 

  143. 143.

    Rapisarda A, Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res. 2012;114:237–67.

    Article  CAS  PubMed  Google Scholar 

  144. 144.

    Siefert SA, Sarkar R. Matrix metalloproteinases in vascular physiology and disease. Vascular. 2012;20:210–6.

    Article  PubMed  Google Scholar 

  145. 145.

    Yin SQ, Wang JJ, Zhang CM, Liu ZP. The development of MetAP-2 inhibitors in cancer treatment. Curr Med Chem. 2012;19:1021–35.

    Article  CAS  PubMed  Google Scholar 

  146. 146.

    Bayless KJ, Johnson GA. Role of the cytoskeleton in formation and maintenance of angiogenic sprouts. J Vasc Res. 2011;48:369–85.

    Article  PubMed  PubMed Central  Google Scholar 

  147. 147.

    Mottet D, Castronovo V. Histone deacetylases: anti-angiogenic targets in cancer therapy. Curr Cancer Drug Targets. 2010;10:898–913.

    Article  CAS  PubMed  Google Scholar 

  148. 148.

    Zetter BR. Angiogenesis and tumor metastasis. Annu Rev Med. 1998;49:407–24.

    Article  CAS  PubMed  Google Scholar 

  149. 149.

    Kubota Y. Tumor angiogenesis and anti-angiogenic therapy. Keio J Med. 2012;61:47–56.

    Article  CAS  PubMed  Google Scholar 

  150. 150.

    Semenza GL. Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology. Trends Mol Med. 2001;7:345–50.

    Article  CAS  PubMed  Google Scholar 

  151. 151.

    Höckel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93:266–76.

    Article  PubMed  Google Scholar 

  152. 152.

    Kung AL, Wang S, Klco JM, Kaelin WG, Livingston DM. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nat Med. 2000;6:1335–40.

    Article  CAS  PubMed  Google Scholar 

  153. 153.

    Bhatnagar I, Kim S-K. Marine antitumor drugs: status, shortfalls and strategies. Mar Drugs. 2010;8:2702–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. 154.

    Champoux JJ. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem. 2001;70:369–413.

    Article  CAS  PubMed  Google Scholar 

  155. 155.

    Green DR, Levine B. To be or not to be? How selective autophagy and cell death govern cell fate. Cell. 2014;157:65–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. 156.

    Mukhtar E, Adhami VM, Khan N, Mukhtar H. Apoptosis and autophagy induction as mechanism of cancer prevention by naturally occurring dietary agents. Curr Drug Targets. 2012;13:1831–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. 157.

    Morselli E, Galluzzi L, Kepp O, Vicencio JM, Criollo A, Maiuri MC, et al. Anti- and pro-tumor functions of autophagy. Biochim Biophys Acta. 2009;1793:1524–32.

    Article  CAS  PubMed  Google Scholar 

  158. 158.

    Gozuacik D, Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 2004;23:2891–906.

    Article  CAS  PubMed  Google Scholar 

  159. 159.

    Pina IC, Gautschi JT, Wang GY, Sanders ML, Schmitz FJ, France D, et al. Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. J Org Chem. 2003;68(10):3866–73.

    Article  CAS  PubMed  Google Scholar 

  160. 160.

    Gu W, Cueto M, Jensen PR, Fenical W, Silverman RB. Microsporins a and B: new histone deacetylase inhibitors from the marine-derived fungus Microsporum cf. gypseum and the solid-phase synthesis of microsporin a. Tetrahedron. 2007;63(28):6535–41.

    Article  CAS  Google Scholar 

  161. 161.

    Nakao Y, Yoshida S, Matsunaga S, Shindoh N, Terada Y, Nagai K, et al. Azumamides A–E: histone deacetylase inhibitory cyclic tetrapeptides from the marine sponge Mycale izuensis. Angew Chem Int Ed. 2006;45(45):7553–7.

    Article  CAS  Google Scholar 

  162. 162.

    Liu Y, Salvador LA, Byeon S, Ying Y, Kwan JC, Law BK, et al. Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor. J Pharmacol Exp Ther. 2010;335(2):351–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. 163.

    Liu T, Kuljaca S, Tee A, Marshall GM. Histone deacetylase inhibitors: multifunctional anticancer agents. Cancer Treat Rev. 2006;32(3):157–65.

    Article  CAS  PubMed  Google Scholar 

  164. 164.

    Tabatabai R, Linhares Y, Bolos D, Mita M, Mita A. Targeting the Wnt pathway in cancer: a review of novel therapeutics. Target Oncol. 2017;12:623–41.

    Article  PubMed  Google Scholar 

  165. 165.

    Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149:1192–205.

    Article  CAS  PubMed  Google Scholar 

  166. 166.

    Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387–98.

    Article  CAS  PubMed  Google Scholar 

  167. 167.

    Galluzzi L, Spranger S, Fuchs E, López-Soto A. WNT signaling in cancer immunosurveillance. Trends Cell Biol. 2018;29:44–65.

    Article  CAS  PubMed  Google Scholar 

  168. 168.

    Wang B, Tian T, Kalland KH, Ke X, Qu Y. Targeting Wnt/beta-catenin signaling for cancer immunotherapy. Trends Pharmacol Sci. 2018;39:648–58.

    Article  CAS  PubMed  Google Scholar 

  169. 169.

    Sherwood V. WNT signaling: an emerging mediator of cancer cell metabolism? Mol Cell Biol. 2015;35:2–10.

    Article  CAS  PubMed  Google Scholar 

  170. 170.

    Nigam M, Ranjan V, Srivastava S, Sharma R, Balapure AK. Centchroman induces G0/G1 arrest and caspase-dependent apoptosis involving mitochondrial membrane depolarization in MCF-7 and MDA MB-231 human breast cancer cells. Life Sci. 2008;82:577–90.

    Article  CAS  PubMed  Google Scholar 

  171. 171.

    Nigam M, Singh N, Ranjan V, Zaidi D, Sharma R, Nigam D, et al. Centchroman mediated apoptosis involves cross-talk between extrinsic/intrinsic pathways and oxidative regulation. Life Sci. 2010;87:750–8.

    Article  CAS  PubMed  Google Scholar 

  172. 172.

    Singh N, Nigam M, Ranjan V, Sharma R, Balapure AK, Rath SK. Caspase mediated enhanced apoptotic action of cyclophosphamide- and resveratrol-treated MCF-7 cells. J Pharmacol Sci. 2009;109:473–85.

    Article  CAS  PubMed  Google Scholar 

  173. 173.

    Singh N, Nigam M, Ranjan V, Zaidi D, Garg VK, Sharma S, et al. Resveratrol as an adjunct therapy in cyclophosphamide-treated MCF-7 cells and breast tumor explants. Cancer Sci. 2011;102:1059–67.

    Article  CAS  PubMed  Google Scholar 

  174. 174.

    Mishra AP, Salehi B, Sharifi-Rad M, Pezzani R, Kobarfard F, Sharifi-Rad J, et al. Programmed cell death, from a cancer perspective: an overview. Mol Diagn Ther. 2018;22:281–95.

    Article  CAS  PubMed  Google Scholar 

  175. 175.

    Kong D, Yamori T, Kobayashi M, Duan H. Antiproliferative and antiangiogenic activities of Smenospongine, a marine sponge sesquiterpene aminoquinone. Mar Drugs. 2011;9:154–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. 176.

    Grienke U, Silke J, Tasdemir D. Bioactive compounds from marine mussels and their effects on human health. Food Chem. 2014;142:48–60.

    Article  CAS  PubMed  Google Scholar 

  177. 177.

    Tornero V, Hanke G. Chemical contaminants entering the marine environment from sea-based sources: a review with a focus on European seas. Mar Pollut Bull. 2016;112:17–38.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Authors are very thankful to all the authors whose work has been cited in this paper. Figures of the compounds has been drawn using ChemDraw software. 

Author information

Affiliations

Authors

Corresponding authors

Correspondence to Mohammad Hosein Farzaei or Abhay Prakash Mishra.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Ethical issues

This study does not involve any animal study or clinical trial itself, hence no ethical issues.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nigam, M., Suleria, H.A.R., Farzaei, M.H. et al. Marine anticancer drugs and their relevant targets: a treasure from the ocean. DARU J Pharm Sci 27, 491–515 (2019). https://doi.org/10.1007/s40199-019-00273-4

Download citation

Keywords

  • Marine bioactive compounds
  • Antiproliferation
  • Cell death
  • Cytotoxic
  • Apoptosis
  • Autophagy