Abstract
Alkaloids are low-molecular-weight nitrogen-containing natural products mostly found in plant and some microorganisms and restricted to few animals also. Historical evidence over time suggests the use of alkaloid both as a medicine and toxicant. The widespread distribution and their wide exhibit of structures make the classification of the alkaloids difficult. Several natural alkaloids display antiproliferation and antimetastasis consequences for different kinds of malignant growths both in vitro and in vivo. This section highlights on the naturally derived alkaloids with potential anticancer properties, highlighting the targeted biomolecules, viz., targeting nucleic acids of different conformation and its associated enzymes, cellular proteins, growth factors, carbohydrates, and lipids. The same natural alkaloids have been accounted to have different target biomolecules for the inhibition of progression and metastasis of specific cancer cells. Since cancer is a disease process driven by many aberrant oncoproteins related to multiple pathways of signal transduction, single-target therapeutic approach is not going to lead to a successful translational application. Thus, development of multitarget agents is an urgent quest for the treatment. Based on these informations, this study may be of prospective use in a framework to design novel anticancer drug molecules for improved therapeutic applications in the future. But further research and clinical trials are necessary before final acceptance.
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References
Adraine C, Creagh EM, Martin SJ (2001) Apoptosis associated release of Smac/DIOBLO from mitochondria requires active caspases and is blocked by Bcl-2. EMBO J 20:6627–6636
Ahmad I, Fakhri S, Khan H, Jeandet P, Aschner M, Yue Z-L (2020) Targeting cell cycle by β-carboline alkaloids in vitro: novel therapeutic prospects for the treatment of cancer. Chem Biol Interact 330(2020):109229. https://doi.org/10.1016/j.cbi.2020.109229
Akhtar S, Achkar IW, Siveen KS, Kuttikrishnan S, Prabhu KS, Khan AQ, Ahmed EI, Sahir F, Jerobin J, Raza A, Merhi M, Elsabah HM, Taha R, El OH, Zayed H et al (2019) Sanguinarine induces apoptosis pathway in multiple myeloma cell lines via inhibition of the JaK2/STAT3 signaling. Front Oncol 9(Article 285):1–15. https://doi.org/10.3389/fonc.2019.00285
Anderson HJ, Coleman JE, Andersen RJ, Roberge M (1997) Cytotoxic peptides hemiasterlin, hemiasterlin a and hemiasterlin b induce mitotic arrest and abnormal spindle formation. Cancer Chemother Pharmacol 39:223–226
Arunachalam K, Chidambaram A, Sankar R, Rajasekaran S, Marshal JJ, Muthusamy K, Ravikumar V (2016) Berberine exhibits chromatin remodeling by modulation of histone deacetylase to induce growth arrest and apoptosis in the A549 cell line. J Agric Food Chem. https://doi.org/10.1021/acs.jafc.6b04453
Azam S, Jouvet N, Jilani A, Vongsamphanh R, Yang X, Yang S, Ramotar D (2008) Human glyceraldehyde-3-phosphate dehydrogenase plays a direct role in reactivating oxidized forms of the DNA repair enzyme APE1. J Biol Chem 283(45):30632–30641
Bhadra K, Maiti M, Suresh Kumar G (2007) Molecular recognition of DNA by small molecules: AT base pair specific intercalative binding of cytotoxic plant alkaloid palmatine. Biochim Biophys Acta 1770:1071–1080
Bhadra K, Suresh Kumar G (2011a) Therapeutic potential of isoquinoline alkaloids: an update on their nucleic acids binding aspects and implications for drug design. Med Res Rev 31(6):821–862
Bhadra K, Suresh Kumar G (2011b) Interaction of berberine, palmatine, coralyne and sanguinarine to quadruplex DNA: a comparative spectroscopic and calorimetric study. Biochim Biophys Acta 1810:485–496
Bhattacharjee P, Sarkar S, Ghosh T, Bhadra K (2018) Therapeutic potential of harmaline, a novel alkaloid, against cervical cancer cells in vitro: apoptotic induction and DNA interaction study. J Appl Biol Biotech 6(04):1–8
Brahmachari G (ed) Bioactive natural products chemistry and biology, Wiley-VCH, Weinheim 2015, Isoquinoline alkaloids and their analogs: nucleic acid and protein binding aspects, and therapeutic potential for drug design, pp 241–277, Suresh Kumar G.
Chen Z-Z (2016) Berberine induced apoptosis of human osteosarcoma cells by inhibiting phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signal pathway activation. Iran J Public Health 45(5):578–585
Chen D, Ma Y, Guo Z, Liu L, Yang Y, Wang Y, Pan B, Wu L, Hui Y, Yang W (2020) Two natural alkaloids synergistically induce apoptosis in breast cancer cells by inhibiting STAT3 activation. Molecules 25:216. https://doi.org/10.3390/molecules25010216
Chmura SJ, Dolan ME, Cha A, Mauceri HJ, Kufe DW, Weichselbaum RR (2000) In vitro and in vivo activity of protein kinase C inhibitor Chelerythrine Chloride induces tumor cell toxicity and growth delay. Clin Cancer Res 6:737–742
Cuadrado A, Garcia-Fernandez LF, Gonzalez L, Suarez Y, Losada A, Alcaide V, Martinez T, Fernandez-Sousa JM, Sanchez-Puelles JM, Munoz A (2003) Aplidin induces apoptosis in human cancer cells via glutathione depletion and sustained activation of the epidermal growth factor receptor, src, jnk, and p38 mapk. J Biol Chem 278:241–250
D’Incalci M, Galmarini CM (2010) A review of trabectedin (et-743): a unique mechanism of action. Mol Cancer Ther 9:2157–2163
Dassonneville L, Wattez N, Baldeyrou B, Mahieu C, Lansiaux A, Banaigs B, Bonnard I, Bailly C (2000) Inhibition of topoisomerase ii by the marine alkaloid ascididemin and induction of apoptosis in leukemia cells. Biochem Pharmacol 60:527–537
Dey P, Kundu A, Chakraborty HJ, Kar B, Choi WS, Lee BM, Bhakta T, Atanasov AG, Kim HS (2019) Therapeutic value of steroidal alkaloids in cancer: current trends and future perspectives. Int J Cancer 145:1731–1744
Fan M, Chen G, Sun B, Wu J, Li N, Sarker SD, Nahar L, Guo M (2019) Screening for natural inhibitors of human topoisomerases from medicinal plants with bio-affinity ultrafiltration and LC–MS. Phytochem Rev. https://doi.org/10.1007/s11101-019-09635-x
Fang FG. Synthetic studies on the halichondrin b analog, E7389. Abstract presented at Frontiers in chemistry and medicine I, 11 November 2004
Farouk L, Laroubi A, Aboufatima R, Benharref A, Chait A (2008) Evaluation of the analgesic effect of alkaloid extract of Peganum harmala L.: possible mechanisms involved. J Ethnopharmacol 115(3):449–54. https://doi.org/10.1016/j.jep.2007.10.014
Fedorov SN, Bode AM, Stonik VA, Gorshkova IA, Schmid PC, Radchenko OS, Berdyshev EV, Dong Z (2004) Marine alkaloid polycarpine and its synthetic derivative dimethylpolycarpine induce apoptosis in jb6 cells through p53- and caspase 3-dependent pathways. Pharm Res 21:2307–2319
Ganesan K, Xu B (2018) Telomerase inhibitors from natural products and their anticancer potential. Int J Mol Sci 19:13. https://doi.org/10.3390/ijms19010013
Gao J-L, Chen Y-G (2015) Natural compounds regulate glycolysis in hypoxic tumor microenvironment. Hindawi publishing corporation. BioMed Res Int 2015, Article ID 354143, 8 p. https://doi.org/10.1155/2015/354143
Goldthwait DA (1960) Nucleic acids and Cancer. Am J Med 29(6):P1034–P1059. https://doi.org/10.1016/0002-9343(60)90083-8
Gong X, Chen Z, Han Q, Chen C, Jing L, Liu Y, Zhao L, Yao X, Sun X (2018) Sanguinarine triggers intrinsic apoptosis to suppress colorectal cancer growth through disassociation between STRAP and MELK. BMC Cancer 18:578–593
Gross H, Goeger DE, Hills P, Mooberry SL, Ballantine DL, Murray TF, Valeriote FA, Gerwick WH (2006) Lophocladines, bioactive alkaloids from the red alga lophocladia sp. J Nat Prod 69:640–644
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 22:250. https://doi.org/10.3390/molecules22020250
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70. https://doi.org/10.1016/S0092-8674(00)81683-9
Heinrich M, Barnes J, Gibbons S, Williamson EM (2012) Fundamentals of pharmacognosy and phytotherapy. Elsevier Health Sciences, p 130. 978-0702052316
Hossain F, Andreana PR (2019) Developments in carbohydrate-based cancer therapeutics. Pharmaceuticals 12:84. https://doi.org/10.3390/ph12020084
Kim WS, Lee YS, Cha SH, Jeong HW, Choe SS, Lee M-R, Oh GT et al (2009) Controlling central and peripheral AMPK activity Berberine improves lipid dysregulation in obesity. Am J Physiol Endocrinol Metab 296:E812–E819. https://doi.org/10.1152/ajpendo.90710.2008
Kumar A, Jaitak V (2019) Natural products as multidrug resistance modulators in cancer. Eur J Med Chem 176:268–291. https://doi.org/10.1016/j.ejmech.2019.05.027
Li L, Dai HJ, Ye M, Wang SL, Xiao XJ, Zheng J, Chen HY, Luo YH, Liu J (2012) Lycorine induces cell-cycle arrest in the G0/G1 phase in K562 cells via HDAC inhibition. Cancer Cell Int 12:49
Liu M, Zhao G, Cao S, Zhang Y, Li X, Lin X (2017) Development of certain protein kinase inhibitors with the components from traditional chinese medicine. Front Pharmacol. https://doi.org/10.3389/fphar.2016.00523
Lu J-J, Bao J-L, Chen X-P, Huang M, Wang Y-T (2012) Alkaloids isolated from natural herbs as the anticancer agents, Evid Based Complement Alternat Med Article ID 485042, pg 1–12. doi:https://doi.org/10.1155/2012/485042. Hindawi Publishing Corporation
Maiti M, Suresh Kumar G (2010, 2010) Polymorphic nucleic acid binding of bioactive isoquinoline alkaloids and their role in cancer. J Nucleic Acids:593408, 23 pages. https://doi.org/10.4061/2010/593408. SAGE-Hindawi Access to Research
Mao L, Chen Q, Gong K, Xu X, Xie Y, Zhang W, Cao H, Hu T, Hong X, Zhan Y-Y (2018) Berberine decelerates glucose metabolism via suppression of mTOR-dependent HIF-1α protein synthesis in colon cancer cells. Oncol Rep. https://doi.org/10.3892/or.2018.6318
Matsuda D, Satoshi Ohte S, Ohshiro T, Jiang W, Rudel LL, Hong B, Si S, Tomoda H (2008) Molecular target of piperine in the inhibition of lipid droplet accumulation in macrophages. Biol Pharm Bull 31(6):1063–1066
Matsuura HN, Fett-Neto AG (2017) Plant alkaloids: main features, toxicity and mechanisms of action; plant toxins. Springer, Dordrecht, pp 243–261
Moser BR (2008) Review of cytotoxic cephalostatins and ritterazines: isolation and synthesis. J Nat Prod 1:487–489
O’Connor SE (2008) Alkaloid biosynthesis. In: Wiley encyclopedia of chemical biology. https://doi.org/10.1002/9780470048672.wecb004
Pla D, Albericio F, Alvarez M (2008) Recent advances in lamellarin alkaloids: isolation, synthesis and activity. Anti Cancer Agents Med Chem 8:746–760
Pofahl M, Wengel J, Gunter Mayer G (2014) Multifunctional nucleic acids for tumor cell treatment. Nucleic Acid Ther 24(2). https://doi.org/10.1089/nat.2013.0472
Russo P, Cesario A (2012) New anticancer drugs from marine cyanobacteria. Curr Drug Targets 13:1048–1053
Sanchez ES (ed) (2015) Alkaloids biosynthesis, biological roles and health benefits, biochemistry research trend. Nova Science Publishers, Inc., New York
Sarkar S, Bhadra K (2018) Therapeutic role of harmalol targeting nucleic acids: biophysical perspective and in vitro cytotoxicity. Mini-Rev Med Chem. https://doi.org/10.2174/1389557518666171211164830
Sarkar S, Bhattacharjee P, Ghosh T, Bhadra K (2020) Pharmaceutical efficacy of harmalol in inhibiting hepatocellular carcinoma. Futur J Pharm Sci 6(29):1–18. https://doi.org/10.1186/s43094-020-00045-x
Seca AM, Pinto DC (2018) Plant secondary metabolites as anticancer agents: successes in clinical trials and therapeutic application. Int J Mol Sci 19:263
Shi C-C, Liao J-F, Chen C-F (2001) Comparative study on the vasorelaxant effects of three harmala alkaloids in vitro. Jpn. J Pharmacol 85:299–305
Shweta S, Hima Bindu J, Raghu J, Suma HK, Manjunatha BL, Mohana Kumara P, Ravikanth G, Nataraja KN, Ganeshaiah KN, Uma Shaanker R (2013) Isolation of endophytic bacteria producing the anti-cancer alkaloid camptothecine from Miquelia dentata Bedd. (Icacinaceae). Phytomedicine 20:913–917
Siva GV, Babu CS (2014) Targeting study of plant alkaloid Berberine act as a natural drug inhibitor of Hsp90(heat shock proteins). Int J ChemTech Res 7(5):2130–2132
Sivanesan S, Taylor A, Zhang J, Bakovic M (2018) Betaine and choline improve lipid homeostasis in obesity by participation in mitochondrial oxidative demethylation. Front Nutr. https://doi.org/10.3389/fnut.2018.00061
Song X, Xiong Y, Qi X, Tang W, Dai J, Gu Q, Li J (2018) Molecular targets of active anticancer compounds derived from marine sources. Mar Drugs 16:175. https://doi.org/10.3390/md16050175
Tamaoki T, Nomoto H, Takahashi I et al (1986) Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135:397–402
Tinoush B, Shirdel I, Wink M (2020) Phytochemicals: potential lead molecules for MDR reversal. Front Pharmacol. https://doi.org/10.3389/fphar.2020.00832
Tohme R, Darwiche N, Gali-Muhtasib H (2011) A journey under the sea: the quest for marine anti-cancer alkaloids. Molecules 16:9665–9696. https://doi.org/10.3390/molecules16119665
Viana J de O, Félix MB, Maia M dos S, Serafim V de L, Scotti L, Scotti MT (2018) Drug discovery and computational strategies in the multitarget drugs era. Braz J Pharm Sci 54(Special):e01010. https://doi.org/10.1590/s2175-97902018000001010
Vrba J, Doležel P, Vièar J, Modrianský M, Ulrichová J (2008) Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells. Toxicology in Vitro 22:1008–1017
Wu S, Powers S, Zhu W, Hannun YA (2016) Substantial contribution of extrinsic risk factors to cancer development. Nature 529(7584):43–47
Yang R, Piperdi S, Gorlick R (2008) Activation of the RAF/Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase/Extracellular pathway mediates apoptosis induced by Chelerythrine in osteosarcoma. Clin Cancer Res 14:6396–6404
Yu CR, Mandlekar S, Tan TH, Kong AN (2000) Activation of p38 and c-Jun N-terminal kinase pathways and induction of apoptosis by chelerythrine do not require inhibition of protein kinase. J Biol Chem 275:9612–9619. https://doi.org/10.1074/jbc.275.13.9612
Zhang Y, Huang W-R (2019) Sanguinarine induces apoptosis of human lens epithelial cells by increasing reactive oxygen species via the MAPK signaling pathway. Mol Med Rep. https://doi.org/10.3892/mmr.2019.10087
Zhang X, Gu L, Li J et al (2010) Degradation of MDM2 by the interaction between berberine and DAXX leads to potent apoptosis in MDM2-overexpressing cancer cells. Cancer Res 70(23):9895–9904
Zhang D, Yang R, Wang S et al (2014) Paclitaxel: new uses for an old drug. Drug Des Devel Ther 8:279
Zhang C, Deng J, Liu D, Tuo X, Xiao L, Lai B, Yao Q, Liu J, Yang H, Wang N (2018) Nuciferine ameliorates hepatic steatosis in high-fat diet/streptozocin-induced diabetic mice through a PPARα/PPARγ coactivator-1α pathway. Br J Pharmacol 175:4218–4228
Zhang H, Yang L, Wang Y, Huang W, Li Y, Chen S, Song G, Ren L (2020) Oxymatrine alleviated hepatic lipid metabolism via regulating miR-182 in non-alcoholic fatty liver disease. Life Sci 257:118090. https://doi.org/10.1016/j.lfs.2020.118090
Acknowledgments
KB is indebted to the Council of Scientific and Industrial Research (CSIR) Government of India 37 (1538)/12/EMR-II; U.G.C., Government of India 41-1434/2012(SR) and DST-RFBR, 2017-19, DST/INT/RUS/RFBR/P-254 for the financial support. The author is also grateful to DST-PURSE, DST-FIST SR/FST/LSI-467/2010C) and PRG, University of Kalyani, 2021–22 for the partial financial support.
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Bhadra, K. (2022). Anticancer Natural Alkaloids as Drug Bank Targeting Biomolecules. In: Hussain, C.M., Di Sia, P. (eds) Handbook of Smart Materials, Technologies, and Devices. Springer, Cham. https://doi.org/10.1007/978-3-030-84205-5_94
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