A Marine Natural Products as Modulators of Multidrug Resistance


  • Tatjana P. Stanojkovic Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
  • Sanja Milovic Faculty of Pharmacy, University of Belgrade, VojvodeStepe 450, 11221 Belgrade, Serbia




Multidrug resistance, Chemotherapy, ABC transporters, P-glycoprotein, MDR modulators, Cytoprotective activity, Quantitative structure-activity relationship (QASR).


Multidrug resistance (MDR) which enable the tumor cells to possess intrinsic or acquired cross resistance to multiple chemotherapeutic agents simultaneously is considered to be a major challenge in cancer chemotherapy during the 21st century. numerous efflux pumps and transport proteins have been found to play important roles in MDR either the phenomenon of lowering the total intracellular retention of chemotherapeutic drugs or the redistribution of intracellular accumulation of drugs away from target organelles are two of the basic mechanisms involved in this process of MDR by transmembrane proteins which are expressed in varying concentrations in different neoplasms. Multiple compounds that have the potential to inhibit these pumps or proteins can be a future prospective for adjuvant treatment of neoplastic conditions. In this regard, compounds derived from natural products bear the advantages of low-cost and relative nontoxicity thus providing a great pool of lead structures for chemical derivatizations. This review gives an overview on chemical substances isolated from natural products of marine origin which possess the MDR modulating properties


Gottesman MM, Fojo T,Bates SE. Multidrug resistance in cancer: role of ATP–dependent transporters. Nat Rev Cancer 2002; 2(1): 48-58. https://doi.org/10.1038/nrc706 DOI: https://doi.org/10.1038/nrc706

Avendaño C, Menendez J. Inhibitors of multidrug resistance to antitumor agents (MDR). Curr Med Chem 2002; 9(2): 159-193. https://doi.org/10.2174/0929867023371175 DOI: https://doi.org/10.2174/0929867023371175

Ullah MF. Cancer multidrug resistance (MDR): a major impediment to effective chemotherapy. Asian Pac J Cancer Prev 2008; 9(1): 1-6.

Wu CP, Ohnuma S, Ambudkar SV. Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 2011; 12(4): 609-620. https://doi.org/10.2174/138920111795163887 DOI: https://doi.org/10.2174/138920111795163887

Ambudkar SV, Dey S, Hrycyna CA, Ramachandra M, Pastan I, Gottesman MM. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu Rev Pharmacol Toxicol 1999; 39(1): 361-398. https://doi.org/10.1146/annurev.pharmtox.39.1.361 DOI: https://doi.org/10.1146/annurev.pharmtox.39.1.361

Pluchino KM, Hall MD, Goldsborough AS, Callaghan R, Gottesman MM. Collateral sensitivity as a strategy against cancer multidrug resistance. Drug Resist Updat 2012; 15(1-2): 98-105. https://doi.org/10.1016/j.drup.2012.03.002 DOI: https://doi.org/10.1016/j.drup.2012.03.002

Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993; 62(1): 385-427. https://doi.org/10.1146/annurev.bi.62.070193.002125 DOI: https://doi.org/10.1146/annurev.bi.62.070193.002125

Szakács G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006; 5(3): 219-234. https://doi.org/10.1038/nrd1984

Zhou SF. Structure, function and regulation of P-glycoprotein and its clinical relevance in drug disposition. Xenobiotica 2008; 38(7-8): 802-832. https://doi.org/10.1080/00498250701867889 DOI: https://doi.org/10.1080/00498250701867889

Fox E, Bates SE. Tariquidar (XR9576): a P-glycoprotein drug efflux pump inhibitor. Expert Re Anticancer Ther 2007; 7(4): 447-459. https://doi.org/10.1586/14737140.7.4.447 DOI: https://doi.org/10.1586/14737140.7.4.447

Shukla S, Wu CP, Ambudkar SV. Development of inhibitors of ATP-binding cassette drug transporters–present status and challenges. Expert Opin Drug Metab Toxicol 2008; 4(2): 205-223. https://doi.org/10.1517/17425255.4.2.205 DOI: https://doi.org/10.1517/17425255.4.2.205

Pusztai L, Wagner P, Ibrahim N, Rivera E, Theriault R, Booser D, et al. Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma. Cancer 2005; 104(4): 682-691. https://doi.org/10.1002/cncr.21227 DOI: https://doi.org/10.1002/cncr.21227

Szakács G, Paterson JK, Ludwig JA, Booth-Genthe C, Gottesman MM. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006; 5(3): 219-234. https://doi.org/10.1038/nrd1984 DOI: https://doi.org/10.1038/nrd1984

Velingkar VS, Dandekar VD. Modulation od P-glycoprotein mediated multidrug resistance (MDR) in cancer using chemosensitiziers. J Pharm Sci Res 2010; 1(2): 104-111.

Krishna R, Mayer LD. Multidrug resistance (MDR) in cancer: mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci 2000; 11(4): 265-283. DOI: https://doi.org/10.1016/S0928-0987(00)00114-7

Lampidis TJ, Krishan A, Planas L, Tapiero H. Reversal of intrinsic resistance to adriamycin in normal cells by verapamil. Cancer Drug Deliv 1986; 3(4): 251-259. https://doi.org/10.1089/cdd.1986.3.251 DOI: https://doi.org/10.1089/cdd.1986.3.251

Ford JM, Hait WN. Pharmacology of drugs that alter multidrug resistance in cancer. Pharmacol Rev 1990; 42(3): 155-199.

Höll V, Kouba M, Dietel M, Vogt G. Stereoisomers of calcium antagonists which differ markedly in their potencies as calcium blockers are equally effective in modulating drug transport by P-glycoprotein. Biochem Pharmacol 1992; 43(12): 2601-2608. https://doi.org/10.1016/0006-2952(92)90149-D DOI: https://doi.org/10.1016/0006-2952(92)90149-D

te Boekhorst PA, van Kapel J, Schoester M, Sonneveld P. Reversal of typical multidrug resistance by cyclosporin and its non-immunosuppressive analogue SDZ PSC 833 in Chinese hamster ovary cells expressing the mdr 1 pheno-type. Cancer Chemother Pharmacol 1992; 30(3): 238-242. https://doi.org/10.1007/BF00686322 DOI: https://doi.org/10.1007/BF00686322

Roe M, Folkes A, Ashworth P, Brumwell J, Chima L, Hunjan S, et al. Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg Med Chem Lett 1999; 9(4): 595-600. https://doi.org/10.1016/S0960-894X(99)00030-X DOI: https://doi.org/10.1016/S0960-894X(99)00030-X

Ullah MF. Cancer multidrug resistance (MDR): a major impediment to effective chemotherapy. Asian Pac J Cancer Prev 2008; 9(1): 1-6.

Liscovitch M,Lavie Y. Cancer multidrug resistance: a review of recent drug discovery research. Drugs 2002; 5(4): 349-355.

Limtrakul P, Siwanon S, Yodkeeree S, Duangrat C. Effect of Stemona curtisii root extract on P-glycoprotein and MRP-1 function in multidrug-resistant cancer cells. Phytomedicine 2007; 14(6): 381-389. https://doi.org/10.1016/j.phymed.2007.03.006 DOI: https://doi.org/10.1016/j.phymed.2007.03.006

Chearwae W, Anuchapreeda S, Nandigama K, Ambudkar SV, Limtrakul P. Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by curcumin I, II, and III purified from Turmeric powder. Biochem Pharmacol 2004; 68(10): 2043-2052. https://doi.org/10.1016/j.bcp.2004.07.009 DOI: https://doi.org/10.1016/j.bcp.2004.07.009

Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anti-cancer agents. Chem Rev 2009; 109(7): 3012-3043. https://doi.org/10.1021/cr900019j DOI: https://doi.org/10.1021/cr900019j

Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012; 75(3): 311-335. https://doi.org/10.1021/np200906s DOI: https://doi.org/10.1021/np200906s

Hu GP, Yuan J, Sun L, She ZG, Wu JH, Lan XJ, et al. Statistical research on marine natural products based on data obtained between 1985 and 2008. Mar Drugs 2011; 9(4): 514-525. https://doi.org/10.3390/md9040514 DOI: https://doi.org/10.3390/md9040514

Stanojković TP, Scaron K, Zdunić G, Kljajić Z, Grozdanić N, Antić J. In vitro antitumoral activities of Padina pavonia on human cervix and breast cancer cell lines. J Med Plant Res 2013; 7(8): 419-424.

BožićT, Novaković I, Gašić MJ, Juranić Z, Stanojković T, Tufegdžić S, et al. Synthesis and biological activity of derivatives of the marine quinone avarone. Eur J Med Chem 2010; 45(3): 923-929. https://doi.org/10.1016/j.ejmech.2009.11.033 DOI: https://doi.org/10.1016/j.ejmech.2009.11.033

Sipkema D, Franssen MC, Osinga R, Tramper J, Wijffels RH. Marine sponges as pharmacy. Mar Biotechnol 2005; 7(3): 142-162. https://doi.org/10.1007/s10126-004-0405-5 DOI: https://doi.org/10.1007/s10126-004-0405-5

Sima P, Vetvicka V. Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Porifera and Coelenterata. World J Clin Oncol 2011; 2(11): 355-361. https://doi.org/10.5306/wjco.v2.i11.355 DOI: https://doi.org/10.5306/wjco.v2.i11.355

Murti Y, Agrawal T. Marine derived pharmaceuticals-develop-ment of natural health products from marine biodiversity. Int J Chem Tech Research 2010; 2(4): 2198-2217.

Yu Z, Lang G, Kajahn I, Schmaljohann R, Imhoff JF. Scopularides A and B, cyclodepsipeptides from a marine sponge-derived fungus, Scopulariopsis brevicaulis. J Nat Prod 2008; 71(6): 1052-1054. https://doi.org/10.1021/np070580e DOI: https://doi.org/10.1021/np070580e

Gademann K, Sieber S. Chemical interference of biological systems with natural products. CHIMIA 2011; 65(11): 835-838. https://doi.org/10.2533/chimia.2011.835 DOI: https://doi.org/10.2533/chimia.2011.835

Patil BS, Jayaprakasha GK, Chidambara Murthy KN, Vikram A. Bioactive compounds: historical perspectives, opportunities, and challenges. J Agric Food Chem 2009; 57(18): 8142-8160. https://doi.org/10.1021/jf9000132 DOI: https://doi.org/10.1021/jf9000132

Crozier A, Jaganath IB, Clifford MN. Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 2009; 26(8): 1001-1043. https://doi.org/10.1039/b802662a DOI: https://doi.org/10.1039/b802662a

Abraham I, El Sayed K, Chen ZS, Guo H. Current status on marine products with reversal effect on cancer multidrug resistance. Mar Drugs 2012; 10(10): 2312-2321. https://doi.org/10.3390/md10102312

Chung SY, Sung MK, Kim NH, Jang JO, Go EJ, Lee HJ.Inhibition of P-glycoprotein by natural products in human breast cancer cells. Arch Pharm Res 2005; 28(7): 823-828. https://doi.org/10.1007/BF02977349 DOI: https://doi.org/10.1007/BF02977349

Haefner B. Drugs from the deep: marine natural products as drug candidates. Drug Discov Today 2003; 8(12): 536-544. https://doi.org/10.1016/S1359-6446(03)02713-2 DOI: https://doi.org/10.1016/S1359-6446(03)02713-2

Garcia-Fernandez LF, Reyes F, Sanchez-Puelles JM. The marine pharmacy: new antitumoral compounds from the sea. Pharm News 2002; 9(6): 495-502.

Lechtenberg M, Schepmann D, Niehues M, Hellenbrand N, Wunsch B, Hensel A. Quality and functionality of saffron: quality control, species assortment and affinity of extract and isolated saffron compounds to NMDA and sigma~ 1 (sigma-1) receptors. Planta Med 2008; 74(7):772-764. https://doi.org/10.1055/s-2008-1074535 DOI: https://doi.org/10.1055/s-2008-1074535

Chakraborty C, Hsu CH, Wen ZH, Lin CS. Anticancer drugs discovery and development from marine organisms. Curr Top Med Chem 2009; 9(16): 1536-1545. https://doi.org/10.2174/156802609789909803 DOI: https://doi.org/10.2174/156802609789909803

Sawadogo WR, Schumacher M, Teiten MH, Cerella C, Dicato M, Diederich M. A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011. Molecules 2013; 18(4): 3641-3673. https://doi.org/10.3390/molecules18043641 DOI: https://doi.org/10.3390/molecules18043641

Senthilkumar K, Kim SK. Marine invertebrate natural products for anti-inflammatory and chronic diseases. Evid Based Complement Alternat Med 2013; 2013: 1-10. https://doi.org/10.1155/2013/572859 DOI: https://doi.org/10.1155/2013/572859

Lopez D, Martinez-Luis S. Marine natural products with P-glycoprotein inhibitor properties. Mar Drugs 2014; 12(1): 525-546. https://doi.org/10.3390/md12010525 DOI: https://doi.org/10.3390/md12010525

Mayer AM, 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: 255-265. https://doi.org/10.1016/j.tips.2010.02.005 DOI: https://doi.org/10.1016/j.tips.2010.02.005

Garcia-Carbonero R, Supko JG, Maki RG, Manola J, Ryan DP, Harmon D, et al. Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study. J Clin Oncol 2005; 23(24): 5484-5492. https://doi.org/10.1200/JCO.2005.05.028 DOI: https://doi.org/10.1200/JCO.2005.05.028

McBride A, Butler SK. Eribulin mesylate: a novel halichondrin B analogue for the treatment of metastatic breast cancer. Am J Health Syst Pharm 2012; 69(9): 745-755. https://doi.org/10.2146/ajhp110237 DOI: https://doi.org/10.2146/ajhp110237

Dyshlovoy SA. Honecker F. Marine compounds and cancer: The first two decades of XXI century. Mar Drugs 2020; 18(1): 20-24. https://doi.org/10.3390/md18010020 DOI: https://doi.org/10.3390/md18010020

Hanna KS. Enfortumab vedotin to treat urothelial carcinoma. Drugs Today (Barc) 2020; 56(5): 329-335. https://doi.org/10.1358/dot.2020.56.5.3127027 DOI: https://doi.org/10.1358/dot.2020.56.5.3127027

Markham A. Belantamab M. First Approval. Drugs 2020; 80: 1607–1613. https://doi.org/10.1007/s40265-020-01404-x DOI: https://doi.org/10.1007/s40265-020-01404-x

Australian Public Assessment Report; The Therapeutic Goods Administration, Department of Health, Australian Government: Symonston, Australia for Plitidepsin. Available from: https://www.tga.gov.au/sites/default/files/auspar-plitidepsin-190513.pdf

Markham, A. Lurbinectedin: First Approval. Drugs 2020; 80: 1345-1353. https://doi.org/10.1007/s40265-020-01374-0 DOI: https://doi.org/10.1007/s40265-020-01374-0

Shi Z, Jain S, Kim IW, Peng XX, Abraham I, Youssef DT, et al. Sipholenol A, a marine‐derived sipholane triterpene, potently reverses P‐glycoprotein (ABCB1)‐mediated multidrug resistance in cancer cells. Cancer Sci 2007; 98(9): 1373-1380. https://doi.org/10.1111/j.1349-7006.2007.00554.x DOI: https://doi.org/10.1111/j.1349-7006.2007.00554.x

Jain S, Abraham I, Carvalho P, Kuang YH, Shaala LA, Youssef DT, et al. Sipholane triterpenoids: Chemistry, reversal of ABCB1/P-glycoprotein-mediated multidrug resistance, and pharmacophore modeling. J Nat Prod 2009; 72(7): 1291-1298. https://doi.org/10.1021/np900091y DOI: https://doi.org/10.1021/np900091y

Aoki S, Yoshioka Y, Miyamoto Y, Higuchi K, Setiawan A, Murakami N, et al. Agosterol A, a novel polyhydroxylated sterol acetate reversing multidrug resistance from a marine sponge of Spongia sp. Tetrahedron Lett 1998; 39(35): 6303-6306. https://doi.org/10.1016/S0040-4039(98)01336-7 DOI: https://doi.org/10.1016/S0040-4039(98)01336-7

Aoki S, Chen ZS, Higasiyama K, Setiawan I, Akiyama SI, Kobayashi M. Reversing effect of agosterol A, a spongean sterol acetate, on multidrug resistance in human carcinoma cells. Jpn J Cancer Res 2001; 92(8): 886-895. https://doi.org/10.1111/j.1349-7006.2001.tb01177.x DOI: https://doi.org/10.1111/j.1349-7006.2001.tb01177.x

Chen ZS, Aoki S, Komatsu M, Ueda K, Sumizawa T, Furukawa T, et al. Reversal of drug resistance mediated by multidrug resistance protein (MRP) 1 by dual effects of agosterol A on MRP1 function. Int J Cancer 2001; 93(1): 107-113. https://doi.org/10.1002/ijc.1290 DOI: https://doi.org/10.1002/ijc.1290

Aoki S. Cao L. Matsui K. Rachmat R. Akiyama S.I. Kobayashi M. Kendarimide A, a novel peptide reversing P-glycoprotein-mediated multidrug resistance in tumor cells, from a marine sponge of Haliclona sp. Tetrahedron 2004; 60(33): 7053-7059. https://doi.org/10.1016/j.tet.2003.07.020 DOI: https://doi.org/10.1016/j.tet.2003.07.020

Quesada AR, Grávalos MG, Puentes JF. Polyaromatic alkaloids from marine invertebrates as cytotoxic compounds and inhibitors of multidrug resistance caused by P-glycoprotein. Br J Cancer 1996; 74(5): 677-682. https://doi.org/10.1038/bjc.1996.421 DOI: https://doi.org/10.1038/bjc.1996.421

Kanzaki A, Takebayashi Y, Ren XQ, Miyashita H, Mori S, Akiyama SI, et al. Overcoming multidrug drug resistance in P-glycoprotein/MDR1-overexpressing cell lines by ecteinascidin 743. Mol Cancer Ther 2002; 1(14): 1327-1334.

Carter NJ, Keam SJ. A Review of its Use in Soft Tissue Sarcoma and Ovarian Cancer. Trabectedin. Drugs 2010; 70(3): 355-376. https://doi.org/10.2165/11202860-000000000-00000 DOI: https://doi.org/10.2165/11202860-000000000-00000

Spitaler M, Utz I, Hilbe W, Hofmann J, Grunicke H. PKC-independent modulation of multidrug resistance in cells with mutant (V185) but not wild-type (G185) P-glycoprotein by bryostatin 1. Biochem Pharmacol 1998; 56(7): 861-869. https://doi.org/10.1016/S0006-2952(98)00107-5 DOI: https://doi.org/10.1016/S0006-2952(98)00107-5

Smith CD, Zilfou JT, Stratmann K, Patterson GM,Moore RE. Welwitindolinone analogues that reverse P-glycoprotein-mediated multiple drug resistance. Mol Pharmacol 1995; 47(2): 241-247.

Huang XC, Sun YL, Salim AA, Chen ZS, Capon RJ. Parguerenes: Marine red alga bromoditerpenes as inhibitors of P-glycoprotein (ABCB1) in multidrug resistant human cancer cells. Biochem Pharmacol 2013; 85(9): 1257-1268. https://doi.org/10.1016/j.bcp.2013.02.005 DOI: https://doi.org/10.1016/j.bcp.2013.02.005

Raju R, Piggott AM, Huang XC, Capon RJ. Nocardioazines: A novel bridged diketopiperazine scaffold from a marine-derived bacterium inhibits P-glycoprotein. Org Lett 2011; 13(10): 2770-2773. https://doi.org/10.1021/ol200904v DOI: https://doi.org/10.1021/ol200904v

Smith CD, Zilfou JT, Stratmann K, Patterson GM, Moore RE. Welwitindolinone analogues that reverse P-glycoprotein-mediated multiple drug resistance. Mol Pharmacol 1995; 47(2): 241-247.

Degnan M, Hawkins CJ, Lavin MF, McCaffrey EJ, Parry DL, Van den Brenk AL, et al. New cyclic peptides with cytotoxic activity from the ascidian Lissoclinum patella. J Med Chem 1989; 32(6): 1349-1354. https://doi.org/10.1021/jm00126a034 DOI: https://doi.org/10.1021/jm00126a034

Gunasekera SP, Gunasekera M, Longley RE, Schulte GK. Discodermolide: a new bioactive polyhydroxylated lactone from the marine sponge Discodermia dissoluta. J Org Chem 1990; 55(16): 4912-4915. https://doi.org/10.1021/jo00303a029 DOI: https://doi.org/10.1021/jo00303a029

Kalesse M. The chemistry and biology of discodermolide. ChemBioChem 2000; 1(3): 171-175. https://doi.org/10.1002/1439-7633(20001002)1:3<171::AID-CBIC171>3.0.CO;2-D DOI: https://doi.org/10.1002/1439-7633(20001002)1:3<171::AID-CBIC171>3.0.CO;2-D

Kowalski RJ, Giannakakou P, Gunasekera SP, Longley RE, Day BW, Hamel E. The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells. Mol Pharmacol 1997; 52(4): 613-622. https://doi.org/10.1124/mol.52.4.613 DOI: https://doi.org/10.1124/mol.52.4.613

Dithmer M, Kirsch AM, Richert E, Fuchs S, Wang F, Schmidt H, et al. Fucoidan does not exert anti-tumorigenic effects on uveal melanoma cell lines. Mar Drugs 2017; 15(7): 193-207. https://doi.org/10.3390/md15070193 DOI: https://doi.org/10.3390/md15070193

Chen WH, Wang SK, Duh CY. Polyhydroxylated steroids from the bamboo coral Isis hippuris. Mar Drugs 2011; 9(10): 1829-1839. https://doi.org/10.3390/md9101829 DOI: https://doi.org/10.3390/md9101829

Kljajić Z, Dogović N, Gašić MJ. Sterols in adriatic sea ascidians. Comp Biochem Physiol 1983; 75(3): 519-521. https://doi.org/10.1016/0305-0491(83)90369-3 DOI: https://doi.org/10.1016/0305-0491(83)90369-3

Muller WEG, Diehl-Seifert B, Sobel C, Bechtold A, Kljajic Z,Dorn A Sponge secondary metabolites: biochemical and ultrastructural localization of the antimitotic agent avarol in Dysidea avara. J Histochem Cytochem (1986); 34(12): 1687-1690. https://doi.org/10.1177/34.12.3782777 DOI: https://doi.org/10.1177/34.12.3782777

Müller WEG, Sobel C, Sachsse W, Diehl-Seifert B, Zahn RK, Eich E, et al. Biphasic and differential effects of the cytostatic agents avarone and avarol on DNA metabolism of human and murine T and B lymphocytes. Eur J Cancer Clin Oncol 1986; 22(4): 473-476. https://doi.org/10.1016/0277-5379(86)90114-8 DOI: https://doi.org/10.1016/0277-5379(86)90114-8

Kreuter MH, Bernd A, Holzmann H, Müller-Klieser W, Maidhof A, Weissmann N, et al. Cytostatic activity of aeroplysinin-1 against lymphoma and epithelioma cells. Naturforschung 1989; 44(7-8): 680-688. https://doi.org/10.1515/znc-1989-7-822 DOI: https://doi.org/10.1515/znc-1989-7-822

Kreuter MH, Robitzki A, Chang S, Steffen R, Michaelis M, Kljajić Z, et al. Production of the cytostatic agent aeroplysinin by the sponge Verongia aerophoba in in vitro culture. Comp Biochem Physiol C Toxicol Pharmacol 1992; 101(1): 183-187. https://doi.org/10.1016/0742-8413(92)90217-U DOI: https://doi.org/10.1016/0742-8413(92)90217-U

Pajic I, Kljajic Z, Dogovic N, Sladic D, Juranic Z, Gasic MJ. A novel lectin from the sponge Haliclona cratera: isolation, characterization and biological activity. Comp Biochem Physiol C Toxicol Pharmacol 2002; 132(2): 213-221. https://doi.org/10.1016/S1532-0456(02)00068-6 DOI: https://doi.org/10.1016/S1532-0456(02)00068-6

Fong WF, Wang C, Zhu GY, Leung CH, Yang MS, Cheung HY. Reversal of multidrug resistance in cancer cells by Rhizoma Alismatis extract. Phytomedicine 2007; 14(2-3): 160-165. https://doi.org/10.1016/j.phymed.2006.03.004 DOI: https://doi.org/10.1016/j.phymed.2006.03.004

Engi H, Vasas A, Redei D, Molnár J, Hohmann J. New MDR modulators and apoptosis inducers from Euphorbia species. Anticancer Research 2007; 27(5A): 3451-3458.

Bansal T, Jaggi M, Khar R, Talegaonkar S. Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy. J Pharm Pharmaceut Sci 2009; 12(1): 46-78. https://doi.org/10.18433/J3RC77 DOI: https://doi.org/10.18433/J3RC77

Abraham I, El Sayed K, Chen ZS, Guo H. Current status on marine products with reversal effect on cancer multidrug resistance. Mar Drugs 2012; 10(10): 2312-2321. https://doi.org/10.3390/md10102312 DOI: https://doi.org/10.3390/md10102312




How to Cite

Tatjana P. Stanojkovic, & Sanja Milovic. (2020). A Marine Natural Products as Modulators of Multidrug Resistance . Journal of Cancer Research Updates, 9(1), 96–101. https://doi.org/10.30683/1929-2279.2020.09.11