Abstract
Throughout history, naturally derived molecules have had countless applications in medicine, pharmacy, and biology. This rich reservoir of natural compounds demonstrated great potential in treating various diseases, mainly cancer. Alkaloids, a subfamily of secondary metabolites, are derived from a large variety of organisms including plants, animals, and marine organisms. This group of compounds has exhibited promising anticancer and chemopreventive effects and has been found to chemo-sensitize tumor cells that are resistant to conventional chemotherapy. The remarkable structural diversity of anticancer alkaloids has allowed their use as lead compounds in the treatment of cancer. Chemical derivatization and modifications of alkaloid structures led to the improvement of their therapeutic potential. Many of these second-generation alkaloids are currently commercially available or are in advanced clinical trials, and a major group is still being tested preclinically. Here we provide an overview of alkaloids that are in clinical trials and which are FDA approved. We have classified anticancer alkaloids according to their biological origin and presented an extensive discussion of their mechanism of action and clinical toxicity. The understanding of the mechanism of action and clinical manifestations of anticancer alkaloids is essential for advancing their use and enhancing their efficacy in the clinic.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Almagro L, Fernandez-Perez F, Pedreno MA (2015) Indole alkaloids from Catharanthus roseus: bioproduction and their effect on human health. Molecules 20(2):2973–3000. https://doi.org/10.3390/molecules20022973
Amin A, Gali-Muhtasib H, Ocker M, Schneider-Stock R (2009) Overview of major classes of plant-derived anticancer drugs. Int J Biomed Sci 5(1):1–11
Aung TN, Qu Z, Kortschak RD, Adelson DL (2017) Understanding the effectiveness of natural compound mixtures in cancer through their molecular mode of action. Int J Mol Sci 18(3):1–20. https://doi.org/10.3390/ijms18030656
Barbuti AM, Chen ZS (2015) Paclitaxel through the ages of anticancer therapy: exploring its role in Chemoresistance and radiation therapy. Cancers (Basel) 7(4):2360–2371. https://doi.org/10.3390/cancers7040897
Brousell SC et al (2018) Vinflunine for the treatment of advanced or metastatic transitional cell carcinoma of the urothelial tract: an evidence-based review of safety, efficacy, and place in therapy. Core Evidence 13:1
Butler MS (2008) Natural products to drugs: natural product-derived compounds in clinical trials. Nat Prod Rep 25(3):475–516. https://doi.org/10.1039/b514294f
Casado JA, Río P, Marco E, García-Hernández V, Domingo A, Pérez L et al (2008) Relevance of the Fanconi anemia pathway in the response of human cells to trabectedin. Mol Cancer Ther 7(5):1309. https://doi.org/10.1158/1535-7163.MCT-07-2432. http://mct.aacrjournals.org/content/7/5/1309.abstract
Chan KS, Koh CG, Li HY (2012) Mitosis-targeted anti-cancer therapies: where they stand. Cell Death Dis 3(10):e411. https://doi.org/10.1038/cddis.2012.148
Chhikara BS, Parang K (2010) Development of cytarabine prodrugs and delivery systems for leukemia treatment. Expert Opin Drug Deliv 7(12):1399–1414. https://doi.org/10.1517/17425247.2010.527330
Ciavatta ML, Lefranc F, Carbone M, Mollo E, Gavagnin M, Betancourt T et al (2017) Marine mollusk-derived agents with antiproliferative activity as promising anticancer agents to overcome chemotherapy resistance. Med Res Rev 37(4):702–801. https://doi.org/10.1002/med.21423
Colazingari M (2013) Marine natural resources and technological development: an economic analysis of the wealth from the oceans. Routledge, New York
D’Incalci M, Galmarini CM (2010) A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther 9(8):2157–2163. https://doi.org/10.1158/1535-7163.mct-10-0263
Damlaj M, Lipton JH, Assouline SE (2016) A safety evaluation of omacetaxine mepesuccinate for the treatment of chronic myeloid leukemia. Expert Opin Drug Saf 15(9):1279–1286. https://doi.org/10.1080/14740338.2016.1207760
Demain AL, Vaishnav P (2011) Natural products for cancer chemotherapy. Microb Biotechnol 4(6):687–699. https://doi.org/10.1111/j.1751-7915.2010.00221.x
DeVita VT Jr, DeVita-Raeburn E (2015) The death of cancer: after fifty years on the front lines of medicine, a pioneering oncologist reveals why the war on cancer is winnable – and how we can get there. Sarah Crichton Books, New York
DeVita VT Jr, Chu E (2008) A history of cancer chemotherapy. Cancer Res 68(21):8643–8653. https://doi.org/10.1158/0008-5472.can-07-6611
Diéras V, S L, Romieu G, Tubiana-Hulin M, Lortholary A, Kaufman P et al (2008) Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy. Ann Oncol 19(7):1255–1260
D’Incalci M, Badri N, Galmarini CM, Allavena P (2014) Trabectedin, a drug acting on both cancer cells and the tumour microenvironment. Br J Cancer 111(4):646–650. https://doi.org/10.1038/bjc.2014.149
Donoghue M, Lemery SJ, Yuan W, He K, Sridhara R, Shord S et al (2012) Eribulin mesylate for the treatment of patients with refractory metastatic breast cancer: use of a “physician’s choice” control arm in a randomized approval trial. Clin Cancer Res 18(6):1496–1505. https://doi.org/10.1158/1078-0432.ccr-11-2149
Douer D (2016) Efficacy and safety of vincristine sulfate liposome injection in the treatment of adult acute lymphocytic leukemia. Oncologist 21(7):840–847. https://doi.org/10.1634/theoncologist.2015-0391
Dydal-Hargreaves NF, Risinger AL, Mooberry SL (2015) Eribulin mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res 21(11):2445–2452. https://doi.org/10.1158/1078-0432.ccr-14-3252
Fayette J, Coquard IR, Alberti L, Boyle H, Meeus P, Decouvelaere AV et al (2006) ET-743: a novel agent with activity in soft-tissue sarcomas. Curr Opin Oncol 18(4):347–353. https://doi.org/10.1097/01.cco.0000228740.70379.3f
Ferreira Júnior WS, Cruz MP, Santos LL d, Medeiros MFT (2012) Use and importance of quina (Cinchona spp.) and ipeca (Carapichea ipecacuanha (Brot.) L. Andersson): plants for medicinal use from the 16th century to the present. J Herb Med 2(4):103–112. https://doi.org/10.1016/j.hermed.2012.07.003
Fontana A, Cavaliere P, Wahidulla S, Naik CG, Cimino G (2000) A new antitumor isoquinoline alkaloid from the marine nudibranch Jorunna funebris. Tetrahedron 56(37):7305–7308. https://doi.org/10.1016/S0040-4020(00)00629-3
Fridlender M, Kapulnik Y, Koltai H (2015) Plant derived substances with anti-cancer activity: from folklore to practice (review). Front Plant Sci 6:799. https://doi.org/10.3389/fpls.2015.00799
Funahashi Y, Okamoto K, Adachi Y, Semba T, Uesugi M, Ozawa Y et al (2014) Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. Cancer Sci 105(10):1334–1342. https://doi.org/10.1111/cas.12488
Galmarini CM, Thomas X, Calvo F, Rousselot P, El Jafaari A, Cros E et al (2002) Potential mechanisms of resistance to cytarabine in AML patients. Leuk Res 26(7):621–629
Glantz MJ, Jaeckle KA, Chamberlain MC, Phuphanich S, Recht L, Swinnen LJ et al (1999) A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 5(11):3394–3402
Gordaliza M (2007) Natural products as leads to anticancer drugs. Clin Transl Oncol 9(12):767–776
Guirouilh-Barbat J, Antony S, Pommier Y (2009) Zalypsis (PM00104) is a potent inducer of gamma-H2AX foci and reveals the importance of the C ring of trabectedin for transcription-coupled repair inhibition. Mol Cancer Ther 8(7):2007–2014. https://doi.org/10.1158/1535-7163.mct-09-0336
Habli Z, Toumieh G, Fatfat M, Rahal ON, Gali-Muhtasib H (2017) Emerging cytotoxic alkaloids in the battle against cancer: overview of molecular mechanisms. Molecules 22(2):250. https://doi.org/10.3390/molecules22020250
Hagop K (2016) Acute myeloid leukemia—major progress over four decades and glimpses into the future. Am J Hematol 91(1):131–145. https://doi.org/10.1002/ajh.24246
Hayasaka S, Kodama T, Ohira A (2012) Traditional Japanese herbal (kampo) medicines and treatment of ocular diseases: a review. Am J Chin Med 40(5):887–904. https://doi.org/10.1142/s0192415x12500668
Hirata Y, Uemura D (1986) Halichondrins – antitumor polyether macrolides from a marine sponge. Pure and Applied Chemistry 58(5):701. Available at: https://www.degruyter.com/view/j/pac.1986.58.issue-5/pac198658050701/pac198658050701.xml. Accessed: 2018-05-11t12:37:46.23+02:00
Ho MY, Mackey JR (2014) Presentation and management of docetaxel-related adverse effects in patients with breast cancer. Cancer Manag Res 6:253–259. https://doi.org/10.2147/cmar.s40601
Holton RA, Somoza C, Kim HB, Liang F, Biediger RJ, Boatman PD et al (1994) First total synthesis of taxol. 1. Functionalization of the B ring. J Am Chem Soc 116(4):1597–1598. https://doi.org/10.1021/ja00083a066
Hussain (2012) Marine natural products: a lead for anti-cancer. Indian J Geo-Mar Sci 41(1):27–39
Iqbal J, Abbasi BA, Mahmood T, Kanwal S, Ali B, Shah SA et al (2017) Plant-derived anticancer agents: a green anticancer approach. Asian Pac J Trop Biomed 7(12):1129–1150. https://doi.org/10.1016/j.apjtb.2017.10.016
Isah T (2016) Anticancer alkaloids from trees: development into drugs. Pharmacogn Rev 10(20):90–99. https://doi.org/10.4103/0973-7847.194047
Jones RJ, Hawkins RE, Eatock MM, Ferry DR, Eskens FALM, Wilke H et al (2008) A phase II open-label study of DHA-paclitaxel (Taxoprexin) by 2-h intravenous infusion in previously untreated patients with locally advanced or metastatic gastric or oesophageal adenocarcinoma (journal article). Cancer Chemother Pharmacol 61(3):435–441. https://doi.org/10.1007/s00280-007-0486-8
Jordan MA, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4(4):253–265. https://doi.org/10.1038/nrc1317
Jordan MA, Thrower D, Wilson L (1991) Mechanism of inhibition of cell proliferation by Vinca alkaloids. Cancer Res 51(8):2212–2222
Jordan K, Jahn F, Jordan B, Kegel T, Muller-Tidow C, Russel J (2015) Trabectedin: supportive care strategies and safety profile. Crit Rev Oncol Hematol 94(3):279–290. https://doi.org/10.1016/j.critrevonc.2015.02.012
Kampan NC, Madondo MT, McNally OM, Quinn M, Plebanski M (2015) Paclitaxel and its evolving role in the Management of Ovarian Cancer. Biomed Res Int 2015:413076. https://doi.org/10.1155/2015/413076
Kantarjian HM, O’Brien S, Cortes J (2013) Homoharringtonine/Omacetaxine Mepesuccinate: the long and winding road to food and drug administration approval. Clin Lymphoma Myeloma Leuk 13(5):530–533. https://doi.org/10.1016/j.clml.2013.03.017
Kaur, R. (2015). Alkaloids – important therapeutic secondary metabolites of plants origin
Khazir J, Riley DL, Pilcher LA, De-Maayer P, Mir BA (2014) Anticancer agents from diverse natural sources. Nat Prod Commun 9(11):1655–1669
Koczywas M, Frankel PH, Synold TW, Lenz HJ, Mortimer JE, El-Khoueiry AB et al (2014) Phase I study of the halichondrin B analogue eribulin mesylate in combination with cisplatin in advanced solid tumors. Br J Cancer 111(12):2268–2274. https://doi.org/10.1038/bjc.2014.554
Krug U, Buchner T, Berdel WE, Muller-Tidow C (2011) The treatment of elderly patients with acute myeloid leukemia. Dtsch Arztebl Int 108(51–52):863–870. https://doi.org/10.3238/arztebl.2011.0863
Le VH, Inai M, Williams RM, Kan T (2015) Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics. Nat Prod Rep 32(2):328–347. https://doi.org/10.1039/c4np00051j
Leal JF, Garcia-Hernandez V, Moneo V, Domingo A, Bueren-Calabuig JA, Negri A et al (2009) Molecular pharmacology and antitumor activity of Zalypsis in several human cancer cell lines. Biochem Pharmacol 78(2):162–170. https://doi.org/10.1016/j.bcp.2009.04.003
Leal JFM, Martínez-Díez M, García-Hernández V, Moneo V, Domingo A, Bueren-Calabuig JA et al (2010) PM01183, a new DNA minor groove covalent binder with potent in vitro and in vivo anti-tumour activity. Br J Pharmacol 161(5):1099–1110. https://doi.org/10.1111/j.1476-5381.2010.00945.x
Lewinska A, Chochrek P, Smoląg – Klosowska K, Rawska E, Wnuk M (2015) Oxidant-based anticancer activity of a novel synthetic analogue of capsaicin, capsaicin epoxide. Redox Rep 20(3):116–125. https://doi.org/10.1179/1351000214Y.0000000113
Lheureux S, Oza AM, Laurie SA, Halford R, Jonker D, Chen E et al (2015) A phase I combination dose-escalation study of eribulin mesylate and gemcitabine in patients with advanced solid tumours: a study of the Princess Margaret Consortium. Br J Cancer 113(11):1534–1540. https://doi.org/10.1038/bjc.2015.343
Li Z, Guo JR, Chen QQ, Wang CY, Zhang WJ, Yao MC, et al. (2017) Exploring the antitumor mechanism of high-dose cytarabine through the metabolic perturbations of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia HL-60 cells. Molecules 22(3). doi:https://doi.org/10.3390/molecules22030499
Lu JJ, Bao JL, Chen XP, Huang M, Wang YT (2012) Alkaloids isolated from natural herbs as the anticancer agents. Evid Based Complement Alternat Med 2012:485042. https://doi.org/10.1155/2012/485042
Luduen̄a RF, Roach MC, Prasad V, Pettit GR (1993) Interaction of halichondrin B and homohalichondrin B with bovine brain tubulin. Biochem Pharmacol 45(2):421–427. https://doi.org/10.1016/0006-2952(93)90079-C
Mayer AM, Glaser KB, Cuevas C, Jacobs RS, Kem W, Little RD et al (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci 31(6):255–265. https://doi.org/10.1016/j.tips.2010.02.005
Miller TP, Chase EM, Dorr R, Dalton WS, Lam KS, Salmon SE (1998) A phase I/II trial of paclitaxel for non-Hodgkin’s lymphoma followed by paclitaxel plus quinine in drug-resistant disease. Anti-Cancer Drugs 9(2):135–140
Mohan K, Deepa RJ (2012) Alkaloids as anticancer agents. Annals of Phytomedicine 1(1):46–53
Morgan RJ, Synold TW, Longmate JA, Quinn DI, Gandara D, Lenz HJ et al (2015) Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California Cancer consortium trial. Cancer Chemother Pharmacol 76(5):897–907. https://doi.org/10.1007/s00280-015-2868-7
Moudi M, Go R, Yien CYS, Nazre M (2013) Vinca alkaloids. Int J Prev Med 4(11):1231–1235. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883245/
Mukherjee AK, Basu S, Sarkar N, Ghosh AC (2001) Advances in cancer therapy with plant based natural products. Curr Med Chem 8(12):1467–1486
Naito M, Tsuruo T (1997) New multidrug-resistance-reversing drugs, MS-209 and SDZ PSC 833. Cancer Chemother Pharmacol 40(Suppl):S20–S24
Naito M, Matsuba Y, Sato S, Hirata H, Tsuruo T (2002) MS-209, a quinoline-type reversal agent, potentiates antitumor efficacy of docetaxel in multidrug-resistant solid tumor xenograft models. Clin Cancer Res 8(2):582–588
Newcomb (2004) Flavopiridol: pleiotropic biological effects enhance its anticancer activity. Anti-Cancer Drugs 15:411–419
Newman DJ, Cragg GM (2004) Advanced preclinical and clinical trials of natural products and related compounds from marine sources. Curr Med Chem 11(13):1693–1713
Newman DJ, Cragg GM (2016) Natural products as sources of new drugs from 1981 to 2014. J Nat Prod 79(3):629–661. https://doi.org/10.1021/acs.jnatprod.5b01055
Nobili S, Lippi D, Witort E, Donnini M, Bausi L, Mini E et al (2009) Natural compounds for cancer treatment and prevention. Pharmacol Res 59(6):365–378. https://doi.org/10.1016/j.phrs.2009.01.017
O’Brien S, Rizzieri DA, Vey N, Ravandi F, Krug UO, Sekeres MA et al (2012) Elacytarabine has single-agent activity in patients with advanced acute myeloid leukaemia. Br J Haematol 158(5):581–588. https://doi.org/10.1111/j.1365-2141.2012.09186.x
Petek BJ, Jones RL (2014) PM00104 (Zalypsis(R)): a marine derived alkylating agent. Molecules 19(8):12328–12335. https://doi.org/10.3390/molecules190812328
Pires MM, Emmert D, Hrycyna CA, Chmielewski J (2009) Inhibition of P-glycoprotein-mediated paclitaxel resistance by reversibly linked quinine homodimers. Mol Pharmacol 75(1):92–100. https://doi.org/10.1124/mol.108.050492
Prakash O, Kumar A, Kumar P, Ajeet A (2013) Anticancer potential of plants and natural products: a review. Am J Pharmacol Sci 1(6):104–115. http://pubs.sciepub.com/ajps/1/6/1
Preston JN, Trivedi MV (2012) Eribulin: a novel cytotoxic chemotherapy agent. Ann Pharmacother 46(6):802–811. https://doi.org/10.1345/aph.1Q636
Quant (2014) Overview of neurologic complications of non-platinum cancer chemotherapy. UpToDate, Waltham
Quesada (2006) Anti-angiogenic drugs: from bench to clinical trials. Med Res Rev 26(4):483–530. https://doi.org/10.1002/med.20059
Quintas-Cardama A, Kantarjian H, Cortes J (2009) Homoharringtonine, omacetaxine mepesuccinate, and chronic myeloid leukemia circa 2009. Cancer 115(23):5382–5393. https://doi.org/10.1002/cncr.24601
Reddy JA, Dorton R, Westrick E, Dawson A, Smith T, Xu L-C et al (2007) Preclinical evaluation of EC145, a Folate-Vinca alkaloid conjugate. Cancer Res 67(9):4434–4442. https://doi.org/10.1158/0008-5472.Can-07-0033
Romano G, Costantini M, Sansone C, Lauritano C, Ruocco N, Ianora A (2017) Marine microorganisms as a promising and sustainable source of bioactive molecules. Mar Environ Res 128:58–69. https://doi.org/10.1016/j.marenvres.2016.05.002
Ruiz-Torres V, Encinar JA, Herranz-Lopez M, Perez-Sanchez A, Galiano V, Barrajon-Catalan E et al (2017) An updated review on marine anticancer compounds: the use of virtual screening for the discovery of small-molecule cancer drugs. Molecules 22(7). https://doi.org/10.3390/molecules22071037
Saeki T, Tsuruo T, Sato W, Nishikawsa K (2005) Drug resistance in chemotherapy for breast cancer. Cancer Chemother Pharmacol 56(Suppl 1):84–89. https://doi.org/10.1007/s00280-005-0106-4
Saeki T, Nomizu T, Toi M, Ito Y, Noguchi S, Kobayashi T et al (2007) Dofequidar fumarate (MS-209) in combination with cyclophosphamide, doxorubicin, and fluorouracil for patients with advanced or recurrent breast cancer. J Clin Oncol 25(4):411–417. https://doi.org/10.1200/jco.2006.08.1646
Salim AA, Chin Y–W, Kinghorn AD. (2008). Drug discovery from plants bioactive molecules and medicinal plants chapter. doi: https://doi.org/10.1007/978-3-540-74603-4_1.
Saygin C, Carraway HE (2017) Emerging therapies for acute myeloid leukemia. J Hematol Oncol 10(1):93. https://doi.org/10.1186/s13045-017-0463-6
Seca AML, Pinto D (2018) Plant secondary metabolites as anticancer agents: successes in clinical trials and therapeutic application. Int J Mol Sci 19(1):E263. https://doi.org/10.3390/ijms19010263
Seiter K (2005) Toxicity of the topoisomerase I inhibitors. Expert Opin Drug Saf 4(1):45–53
Shah U, Shah R, Acharya S, Acharya N (2013) Novel anticancer agents from plant sources. Chin J Nat Med 11(1):16–23
Sneader W (2005) Drug discovery: a history. Wiley, Chichester
Solary E, Mannone L, Moreau D, Caillot D, Casasnovas RO, Guy H et al (2000) Phase I study of cinchonine, a multidrug resistance reversing agent, combined with the CHVP regimen in relapsed and refractory lymphoproliferative syndromes. Leukemia 14(12):2085–2094
Solary E, Drenou B, Campos L, de Cremoux P, Mugneret F, Moreau P et al (2003) Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia. Blood 102(4):1202–1210. https://doi.org/10.1182/blood-2002-11-3419
Spigel DR, Greco FA (2008) What is the role of novel Taxanes in non–small-cell lung cancer? Clin Lung Cancer 9:S116–S121. https://doi.org/10.3816/CLC.2008.s.017
Mohammad Abu Taher, Mohammad Abu Bin Nyeem, Md. Masum Billah, Ahammed, Monir, Md (2017) Vinca alkaloid- the second most used alkaloid for cancer treatment- a review. Int J Phys Nutr Phys Educ 2(2):723–727
Taylor CW, Dalton WS, Mosley K, Dorr RT, Salmon SE (1997) Combination chemotherapy with cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD) plus oral quinine and verapamil in patients with advanced breast cancer. Breast Cancer Res Treat 42(1):7–14
Ulukan H, Swaan PW (2002) Camptothecins (journal article). Drugs 62(14):2039–2057. https://doi.org/10.2165/00003495-200262140-00004.
Verma AK, Singh RR (2010) Induced dwarf mutant in Catharanthus roseus with enhanced antibacterial activity. Indian J Pharm Sci 72(5):655–657. https://doi.org/10.4103/0250-474X.78541
Vidal A, Munoz C, Guillen MJ, Moreto J, Puertas S, Martinez-Iniesta M et al (2012) Lurbinectedin (PM01183), a new DNA minor groove binder, inhibits growth of orthotopic primary graft of cisplatin-resistant epithelial ovarian cancer. Clin Cancer Res 18(19):5399–5411. https://doi.org/10.1158/1078-0432.ccr-12-1513
Villa FA, Gerwick L (2010) Marine natural product drug discovery: leads for treatment of inflammation, cancer, infections, and neurological disorders. Immunopharmacol Immunotoxicol 32(2):228–237. https://doi.org/10.3109/08923970903296136
Walker FE (1993) Paclitaxel (TAXOL®): side effects and patient education issues. Semin Oncol Nurs 9(4, Supplement 2):6–10. https://doi.org/10.1016/S0749-2081(16)30036-5
Wang X, Chen Z, Mishra AK, Silva A, Ren W, Pan Z et al (2018) Chemotherapy-induced differential cell cycle arrest in B-cell lymphomas affects their sensitivity to Wee1 inhibition. Haematologica 103(3):466–476. https://doi.org/10.3324/haematol.2017.175992
Weaver BA (2014) How taxol/paclitaxel kills cancer cells. Mol Biol Cell 25(18):2677–2681. https://doi.org/10.1091/mbc.E14-04-0916
Wink M (2015) Modes of action of herbal medicines and plant secondary metabolites. Medicines 2(3):251. http://www.mdpi.com/2305-6320/2/3/251
Wu K, Yang Q, Mu Y, Zhou L, Liu Y, Zhou Q et al (2012) Berberine inhibits the proliferation of colon cancer cells by inactivating Wnt/beta-catenin signaling. Int J Oncol 41(1):292–298. https://doi.org/10.3892/ijo.2012.1423
Yared JA, Tkaczuk KH (2012) Update on taxane development: new analogs and new formulations. Drug Des Devel Ther 6:371–384. https://doi.org/10.2147/dddt.s28997
Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S et al (2014) Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal-epithelial transition (MET) states. Br Cancer 110(6):1497–1505. https://doi.org/10.1038/bjc.2014.80
Yu MJ, Zheng W, Seletsky BM (2013) From micrograms to grams: scale-up synthesis of eribulin mesylate. Nat Prod Rep 30(9):1158–1164. https://doi.org/10.1039/c3np70051h
Zelek L, Yovine A, Brain E, Turpin F, Taamma A, Riofrio M et al (2006) A phase II study of Yondelis® (trabectedin, ET-743) as a 24-h continuous intravenous infusion in pretreated advanced breast cancer. Br J Cancer 94(11):1610–1614. https://doi.org/10.1038/sj.bjc.6603142
Zhang D, Yang R, Wang S, Dong Z (2014) Paclitaxel: new uses for an old drug. Drug Des Devel Ther 8:279–284. https://doi.org/10.2147/dddt.s56801
Zhang H, Dong M, Chen J, Wang H, Tenney K, Crews P (2017) Bioactive secondary metabolites from the marine sponge genus Agelas. Mar Drugs 15(11):351. https://doi.org/10.3390/md15110351
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Ballout, F., Habli, Z., Monzer, A., Rahal, O.N., Fatfat, M., Gali-Muhtasib, H. (2019). Anticancer Alkaloids: Molecular Mechanisms and Clinical Manifestations. In: Sharma, A. (eds) Bioactive Natural Products for the Management of Cancer: from Bench to Bedside. Springer, Singapore. https://doi.org/10.1007/978-981-13-7607-8_1
Download citation
DOI: https://doi.org/10.1007/978-981-13-7607-8_1
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-13-7606-1
Online ISBN: 978-981-13-7607-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)