Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Anticancer Properties of Asian Water Monitor Lizard (Varanus salvator), Python (Malayopython reticulatus) and Tortoise (Cuora kamaroma amboinensis)

Author(s): Shareni Jeyamogan, Naveed A. Khan*, Kuppusamy Sagathevan and Ruqaiyyah Siddiqui

Volume 20, Issue 13, 2020

Page: [1558 - 1570] Pages: 13

DOI: 10.2174/1871520620666200504103056

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Cancer contributes to significant morbidity and mortality despite advances in treatment and supportive care. There is a need for the identification of effective anticancer agents. Reptiles such as tortoise, python, and water monitor lizards are exposed to heavy metals, tolerate high levels of radiation, feed on rotten/germ-infested feed, thrive in unsanitary habitat and yet have prolonged lifespans. Such species are rarely reported to develop cancer, suggesting the presence of anticancer molecules/mechanisms.

Methods: Here, we tested effects from sera of Asian water monitor lizard (Varanus salvator), python (Malayopython reticulatus) and tortoise (Cuora kamaroma amboinensis) against cancer cells. Sera were collected and cytotoxicity assays were performed using prostate cancer cells (PC3), Henrietta Lacks cervical adenocarcinoma cells (HeLa) and human breast adenocarcinoma cells (MCF7), as well as human keratinized skin cells (Hacat), by measuring lactate dehydrogenase release as an indicator for cell death. Growth inhibition assays were performed to determine the effects on cancer cell proliferation. Liquid chromatography mass spectrometry was performed for molecular identification.

Results: The findings revealed that reptilian sera, but not bovine serum, abolished viability of Hela, PC3 and MCF7 cells. Samples were subjected to liquid chromatography mass spectrometry, which detected 57 molecules from V. salvator, 81 molecules from Malayopython reticulatus and 33 molecules from C. kamaroma amboinensis and putatively identified 9 molecules from V. salvator, 20 molecules from Malayopython reticulatus and 9 molecules from C. kamaroma amboinensis when matched against METLIN database. Based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition, 123 potential Anticancer Peptides (ACPs) were identified from 883 peptides from V. salvator, 306 potential ACPs from 1074 peptides from Malayopython reticulatus and 235 potential ACPs from 885 peptides from C. kamaroma amboinensis.

Conclusion: To our knowledge, for the first time, we reported comprehensive analyses of selected reptiles’ sera using liquid chromatography mass spectrometry, leading to the identification of potentially novel anticancer agents. We hope that the discovery of molecules from these animals will pave the way for the rational development of new anticancer agents.

Keywords: Cancer, anticancer agents, cytotoxicity, Hela, PC3, MCF7.

Graphical Abstract
[1]
Parkin, D.M.; Bray, F.; Ferlay, J.; Pisani, P. Estimating the world cancer burden: Globocan 2000. Int. J. Cancer, 2001, 94(2), 153-156.
[http://dx.doi.org/10.1002/ijc.1440] [PMID: 11668491]
[2]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[http://dx.doi.org/10.1002/ijc.29210] [PMID: 25220842]
[3]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[4]
Ehrhardt, H.; Pannert, L.; Pfeiffer, S.; Wachter, F.; Amtmann, E.; Jeremias, I. Enhanced anti-tumour effects of Vinca alkaloids given separately from cytostatic therapies. Br. J. Pharmacol., 2013, 168(7), 1558-1569.
[http://dx.doi.org/10.1111/bph.12068] [PMID: 23186127]
[5]
Song, J.K.; Jo, M.R.; Park, M.H.; Song, H.S.; An, B.J.; Song, M.J.; Han, S.B.; Hong, J.T. Cell growth inhibition and induction of apoptosis by snake venom toxin in ovarian cancer cell via inactivation of nuclear factor κB and signal transducer and activator of transcription 3. Arch. Pharm. Res., 2012, 35(5), 867-876.
[http://dx.doi.org/10.1007/s12272-012-0512-1] [PMID: 22644854]
[6]
Jeyamogan, S.; Khan, N.A.; Siddiqui, R. Animals living in polluted environments are a potential source of anti-tumor molecule(s). Cancer Chemother. Pharmacol., 2017, 80(5), 919-924.
[http://dx.doi.org/10.1007/s00280-017-3410-x] [PMID: 28795217]
[7]
Lehner, A.F.; Rumbeiha, W.; Shlosberg, A.; Stuart, K.; Johnson, M.; Domenech, R.; Langner, H. Diagnostic analysis of veterinary dried blood spots for toxic heavy metals exposure. J. Anal. Toxicol., 2013, 37(7), 406-422.
[http://dx.doi.org/10.1093/jat/bkt048] [PMID: 23861340]
[8]
Tellez, M.; Merchant, M. Biomonitoring heavy metal pollution using an aquatic apex predator, the American alligator, and its parasites. PLoS One, 2015, 10(11) e0142522
[http://dx.doi.org/10.1371/journal.pone.0142522] [PMID: 26555363]
[9]
Schneider, L.; Peleja, R.P.; Kluczkovski, A., Jr; Freire, G.M.; Marioni, B.; Vogt, R.C.; Da Silveira, R. Mercury concentration in the spectacled caiman and black caiman (Alligatoridae) of the Amazon: Implications for human health. Arch. Environ. Contam. Toxicol., 2012, 63(2), 270-279.
[http://dx.doi.org/10.1007/s00244-012-9768-1] [PMID: 22580737]
[10]
Amiri, A.; Namavari, M.; Rashidi, M.; Fahmidehkar, M.A.; Seghatoleslam, A. Inhibitory effects of Cyrtopodion scabrum extract on growth of human breast and colorectal cancer cells. Asian Pac. J. Cancer Prev., 2015, 16(2), 565-570.
[http://dx.doi.org/10.7314/APJCP.2015.16.2.565] [PMID: 25684488]
[11]
Azevedo, F.V.P.V.; Lopes, D.S.; Cirilo Gimenes, S.N.; Achê, D.C.; Vecchi, L.; Alves, P.T.; Guimarães, D.O.; Rodrigues, R.S.; Goulart, L.R.; Rodrigues, V.M.; Yoneyama, K.A.G. Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom. Int. J. Biol. Macromol., 2016, 82, 671-677.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.10.080] [PMID: 26519876]
[12]
Bazaa, A.; Luis, J.; Srairi-Abid, N.; Kallech-Ziri, O.; Kessentini-Zouari, R.; Defilles, C.; Lissitzky, J.C.; El Ayeb, M.; Marrakchi, N. MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration. Matrix Biol., 2009, 28(4), 188-193.
[http://dx.doi.org/10.1016/j.matbio.2009.03.007] [PMID: 19351557]
[13]
Mao, X.; He, S.; Zhang, T.; Guo, X.; Ge, Y.; Ma, C.; Zhang, X. Isolation and characterization of antiproliferative peptides from Chinese three-striped box turtle (Cuora trifasciata). Biotechnol. Appl. Biochem., 2017, 64(6), 827-835.
[http://dx.doi.org/10.1002/bab.1548] [PMID: 27957760]
[14]
Chaeychomsri, W.; Yamkong, S.; Chaeychomsri, S.; Siruntawineti, J. Effects of large volume Crocodile blood collection on hematological values of Siamese Crocodiles (Crocodylus siamensis). J. of Adv. Agricultural Technol., 2016, 3(4), 252-257.
[http://dx.doi.org/10.18178/joaat.3.4.252-257]
[15]
Grigg, G.C.; Cairncross, M. Respiratory properties of the blood of Crocodylus porosus. Respir. Physiol., 1980, 41(3), 367-380.
[http://dx.doi.org/10.1016/0034-5687(80)90083-3] [PMID: 6779366]
[16]
Rohilla, M.S.; Tiwari, P.K. Simple method of blood sampling from Indian freshwater turtles for genetic studies. Acta Herpetol., 2008, 3(1), 65-69.
[17]
Nevarez, J. Crocodilians. In: Manual of Exotic Pet Practice; Elsevier, 2009; pp. 112-135.
[18]
Bush, M.; Smeller, J. Blood collection & injection techniques in snakes. Vet. Med. Small Anim. Clin., 1978, 73(2), 211-214.
[PMID: 245912]
[19]
Flanigan, J.E.; Withers, P.C.; Guppy, M. In vitro metabolic depression of tissues from the aestivating frog Neobatrachus pelobatoides. J. Exp. Biol., 1991, 161(1), 273-283.
[20]
Siddiqui, R.; Jeyamogan, S.; Ali, S.M.; Abbas, F.; Sagathevan, K.A.; Khan, N.A. Crocodiles and alligators: Antiamoebic and antitumor compounds of crocodiles. Exp. Parasitol., 2017, 183, 194-200.
[http://dx.doi.org/10.1016/j.exppara.2017.09.008] [PMID: 28917711]
[21]
Rajendran, K.; Anwar, A.; Khan, N.A.; Siddiqui, R. Brain-eating amoebae: Silver nanoparticle conjugation enhanced efficacy of anti-amoebic drugs against Naegleria fowleri. ACS Chem. Neurosci., 2017, 8(12), 2626-2630.
[http://dx.doi.org/10.1021/acschemneuro.7b00430] [PMID: 29206032]
[22]
Strober, W. Trypan blue exclusion test of cell viability. Curr. Protoc. Immunol., 1997, 21(1), A-3B.
[23]
Psychogios, N.; Hau, D.D.; Peng, J.; Guo, A.C.; Mandal, R.; Bouatra, S.; Sinelnikov, I.; Krishnamurthy, R.; Eisner, R.; Gautam, B.; Young, N.; Xia, J.; Knox, C.; Dong, E.; Huang, P.; Hollander, Z.; Pedersen, T.L.; Smith, S.R.; Bamforth, F.; Greiner, R.; McManus, B.; Newman, J.W.; Goodfriend, T.; Wishart, D.S. The human serum metabolome. PLoS One, 2011, 6(2) e16957
[http://dx.doi.org/10.1371/journal.pone.0016957] [PMID: 21359215]
[24]
Zainal Abidin, S.A.; Rajadurai, P.; Chowdhury, M.E.H.; Ahmad Rusmili, M.R.; Othman, I.; Naidu, R. Cytotoxic, antiproliferative and apoptosis-inducing activity of L-Amino acid oxidase from Malaysian Calloselasma rhodostoma on human colon cancer cells. Basic Clin. Pharmacol. Toxicol., 2018, 123(5), 577-588.
[http://dx.doi.org/10.1111/bcpt.13060] [PMID: 29908095]
[25]
Manavalan, B.; Basith, S.; Shin, T.H.; Choi, S.; Kim, M.O.; Lee, G. MLACP: Machine-learning-based prediction of anticancer peptides. Oncotarget, 2017, 8(44), 77121-77136.
[http://dx.doi.org/10.18632/oncotarget.20365] [PMID: 29100375]
[26]
Mycyk, M.B.; Leikin, J.B. Antidote review: Fomepizole for methanol poisoning. Am. J. Ther., 2003, 10(1), 68-70.
[http://dx.doi.org/10.1097/00045391-200301000-00015] [PMID: 12522524]
[27]
Brent, J.; McMartin, K.; Phillips, S.; Aaron, C.; Kulig, K. Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of methanol poisoning. N. Engl. J. Med., 2001, 344(6), 424-429.
[http://dx.doi.org/10.1056/NEJM200102083440605] [PMID: 11172179]
[28]
Brent, J.; McMartin, K.; Phillips, S.; Burkhart, K.K.; Donovan, J.W.; Wells, M.; Kulig, K. Methylpyrazole for Toxic Alcohols Study Group. Fomepizole for the treatment of ethylene glycol poisoning. N. Engl. J. Med., 1999, 340(11), 832-838.
[http://dx.doi.org/10.1056/NEJM199903183401102] [PMID: 10080845]
[29]
Yi, H.S.; Eun, H.S.; Lee, Y.S.; Jung, J.Y.; Park, S.H.; Park, K.G.; Choi, H.S.; Suh, J.M.; Jeong, W.I. Treatment with 4-methylpyrazole modulated stellate cells and natural killer cells and ameliorated liver fibrosis in mice. PLoS One, 2015, 10(5) e0127946
[http://dx.doi.org/10.1371/journal.pone.0127946] [PMID: 26024318]
[30]
Inan Genç, A.; Gok, S.; Banerjee, S.; Severcan, F. Valdecoxib recovers the lipid composition, order and dynamics in colon cancer cell lines independent of COX-2 expression: An ATR-FTIR spectroscopy study. Appl. Spectrosc., 2017, 71(1), 105-117.
[http://dx.doi.org/10.1177/0003702816654164] [PMID: 27354402]
[31]
Atukorala, I.; Hunter, D.J. Valdecoxib: The rise and fall of a COX-2 inhibitor. Expert Opin. Pharmacother., 2013, 14(8), 1077-1086.
[http://dx.doi.org/10.1517/14656566.2013.783568] [PMID: 23517091]
[32]
Kivitz, A.; Eisen, G.; Zhao, W.W.; Bevirt, T.; Recker, D.P. Randomized placebo-controlled trial comparing efficacy and safety of valdecoxib with naproxen in patients with osteoarthritis. J. Fam. Pract., 2002, 51(6), 530-537.
[PMID: 12100776]
[33]
Daniels, S.E.; Torri, S.; Desjardins, P.J. Valdecoxib for treatment of primary dysmenorrhea. A randomized, double-blind comparison with placebo and naproxen. J. Gen. Intern. Med., 2005, 20(1), 62-67.
[http://dx.doi.org/10.1111/j.1525-1497.2004.30052.x] [PMID: 15693930]
[34]
Choi, S.P.; Kim, S.P.; Nam, S.H.; Friedman, M. Antitumor effects of dietary black and brown rice brans in tumor-bearing mice: Relationship to composition. Mol. Nutr. Food Res., 2013, 57(3), 390-400.
[http://dx.doi.org/10.1002/mnfr.201200515] [PMID: 23281142]
[35]
Deme, P.; Narasimhulu, C.A.; Parthasarathy, S. Identification and evaluation of anti-inflammatory properties of aqueous components extracted from sesame (Sesamum indicum) oil. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1087-1088, 61-69.
[http://dx.doi.org/10.1016/j.jchromb.2018.04.029] [PMID: 29709873]
[36]
Hassan, A.Y.; Sarg, M.T.; Bayoumi, A.H.; Kalaf, F.G.A. Design, synthesis, and anticancer activity of novel fused purine analogues. J. Heterocycl. Chem., 2017, 54(6), 3458-3470.
[http://dx.doi.org/10.1002/jhet.2969]
[37]
Huang, L.H.; Xu, H.D.; Yang, Z.Y.; Zheng, Y.F.; Liu, H.M. Synthesis and anticancer activity of novel C6-piperazine substituted purine steroid-nucleosides analogues. Steroids, 2014, 82, 1-6.
[http://dx.doi.org/10.1016/j.steroids.2013.12.004] [PMID: 24378780]
[38]
Yoon, J.S.; Jarhad, D.B.; Kim, G.; Nayak, A.; Zhao, L.X.; Yu, J.; Kim, H.R.; Lee, J.Y.; Mulamoottil, V.A.; Chandra, G.; Byun, W.S.; Lee, S.K.; Kim, Y.C.; Jeong, L.S. Design, synthesis and anticancer activity of fluorocyclopentenyl-purines and - pyrimidines. Eur. J. Med. Chem., 2018, 155, 406-417.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.003] [PMID: 29906687]
[39]
Hoffmann, K.; Wiśniewska, J.; Wojtczak, A.; Sitkowski, J.; Denslow, A.; Wietrzyk, J.; Jakubowski, M.; Łakomska, I. Rational design of dicarboxylato platinum(II) complexes with purine-mimetic ligands as novel anticancer agents. J. Inorg. Biochem., 2017, 172, 34-45.
[http://dx.doi.org/10.1016/j.jinorgbio.2017.04.003] [PMID: 28477537]
[40]
Ghorab, M.M.; El-Gaby, M.S.A.; Alsaid, M.S.; Elshaier, Y.A.M.M.; Soliman, A.M.; El-Senduny, F.F.; Badria, F.A.; Sherif, A.Y.A. Novel thiourea derivatives bearing sulfonamide moiety as anticancer agents through COX-2 inhibition. Anticancer. Agents Med. Chem., 2017, 17(10), 1411-1425.
[http://dx.doi.org/10.2174/1871520617666170327153735] [PMID: 28356021]
[41]
Saeed, S.; Rashid, N.; Jones, P.G.; Ali, M.; Hussain, R. Synthesis, characterization and biological evaluation of some thiourea derivatives bearing benzothiazole moiety as potential antimicrobial and anticancer agents. Eur. J. Med. Chem., 2010, 45(4), 1323-1331.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.016] [PMID: 20056520]
[42]
National Center for Biotechnology Information; PubChem Database., https://pubchem.ncbi.nlm.nih.gov/compound/44257168[May 20, 2019]; CID=44257168..
[43]
Sud, M.; Fahy, E.; Cotter, D.; Brown, A.; Dennis, E.A.; Glass, C.K.; Merrill, A.H., Jr; Murphy, R.C.; Raetz, C.R.; Russell, D.W.; Subramaniam, S. LMSD: LIPID MAPS structure database. Nucleic Acids Res., 2007, 35(Database issue), D527-D532.https://www.lipidmaps.org/data/LMSDRecord.php?LMID=LMGP02050028
[http://dx.doi.org/10.1093/nar/gkl838] [PMID: 17098933]
[44]
Wei, L.S.; Wee, W.; Siong, J.Y.F.; Syamsumir, D.F. Characterization of anticancer, antimicrobial, antioxidant properties and chemical compositions of Peperomia pellucida leaf extract. Acta Med. Iran., 2011, 49(10), 670-674.
[PMID: 22071643]
[45]
Nalini, P.; Durairaj, B. Antitumor potential of hydroethanolic extract of Annona muricata leaves against dalton’s lymphoma ascites-induced tumor in mice. Asian J. Pharm. Clinical Res., 2018, 11(3), 1-4.
[46]
Panda, S. Vyasamurthy; Sahoo, S.K. A review on medicinal use of cow urine. World J. Pharm. Pharm. Sci., 2018, 7(2), 470-474.
[47]
Amaro, S.; Cánovas, D.; Castellanos, M.; Gállego, J.; Martí-Fèbregas, J.; Segura, T.; Chamorro, A. The URICO-ICTUS study, a phase 3 study of combined treatment with uric acid and rtPA administered intravenously in acute ischaemic stroke patients within the first 4.5h of onset of symptoms. Int. J. Stroke, 2010, 5(4), 325-328.
[http://dx.doi.org/10.1111/j.1747-4949.2010.00448.x] [PMID: 20636718]
[48]
Lu, P.Y.; Ansari, A.; Guan, P.J.; Xu, J.J.; Simonenko, V.; Zhong, T. Gemcitabine derivatives for cancer therapy. WO Patent 2,018,175,323, 2019.
[49]
Lin, Z.M.; Guo, Y.X.; Wang, S.Q.; Wang, X.N.; Chang, W.Q.; Zhou, J.C.; Yuan, H.; Lou, H. Diterpenoids from the Chinese liverwort Heteroscyphus tener and their antiproliferative effects. J. Nat. Prod., 2014, 77(6), 1336-1344.
[http://dx.doi.org/10.1021/np5000507] [PMID: 24940845]
[50]
Wang, S.; Liu, S.S.; Lin, Z.M.; Li, R.J.; Wang, X.N.; Zhou, J.C.; Lou, H.X. Terpenoids from the Chinese liverwort Plagiochila pulcherrima and their cytotoxic effects. J. Asian Nat. Prod. Res., 2013, 15(5), 473-481.
[http://dx.doi.org/10.1080/10286020.2013.785529] [PMID: 23614492]
[51]
Yoon, I.S.; Park, J.H.; Kang, H.J.; Choe, J.H.; Goh, M.S.; Kim, D.D.; Cho, H.J. Poly(D,L-lactic acid)-glycerol-based nanoparticles for curcumin delivery. Int. J. Pharm., 2015, 488(1-2), 70-77.
[http://dx.doi.org/10.1016/j.ijpharm.2015.04.046] [PMID: 25900098]
[52]
Kang, K.; Oh, S.H.; Yun, J.H.; Jho, E.H.; Kang, J-H.; Batsuren, D.; Tunsag, J.; Park, K.H.; Kim, M.; Nho, C.W. A novel topoisomerase inhibitor, daurinol, suppresses growth of HCT116 cells with low hematological toxicity compared to etoposide. Neoplasia, 2011, 13(11), 1043-1057.
[http://dx.doi.org/10.1593/neo.11972] [PMID: 22131880]
[53]
Jelski, W.; Szmitkowski, M. Alcohol Dehydrogenase (ADH) and Aldehyde Dehydrogenase (ALDH) in the cancer diseases. Clin. Chim. Acta, 2008, 395(1-2), 1-5.
[http://dx.doi.org/10.1016/j.cca.2008.05.001] [PMID: 18505683]
[54]
Australian Government. Department of Health: Therapeutic Goods Administration. Australian Public Assessment Report for Fomepizole 2017, 1-72.
[55]
Sommerfeld-Klatta, K.; Przystanowicz, J.; Kowalówka-Zawieja, J.; Zielińska-Psuja, B. Effect of repeated administration of 4-methylpyrazole on renal function and lipid peroxidation products in rat kidney after ethylene glycol poisoning. Environ. Toxicol. Pharmacol., 2017, 56, 290-296.
[http://dx.doi.org/10.1016/j.etap.2017.10.004] [PMID: 29091817]
[56]
Persson, B.; Bergman, T.; Keung, W.M.; Waldenström, U.; Holmquist, B.; Vallee, B.L.; Jörnvall, H. Basic features of class-I alcohol dehydrogenase: Variable and constant segments coordinated by inter-class and intra-class variability. Conclusions from characterization of the alligator enzyme. Eur. J. Biochem., 1993, 216(1), 49-56.
[http://dx.doi.org/10.1111/j.1432-1033.1993.tb18115.x] [PMID: 8365416]
[57]
Aida, M.; Artonins, J. K and L three new isoprenylated flavones from the root bark of Artocarpus heterophyllus Lamk. Heterocycles, 1993, 36, 575-580.
[http://dx.doi.org/10.3987/COM-92-6229]
[58]
Chahar, M.K.; Sharma, N.; Dobhal, M.P.; Joshi, Y.C. Flavonoids: A versatile source of anticancer drugs. Pharmacogn. Rev., 2011, 5(9), 1-12.
[http://dx.doi.org/10.4103/0973-7847.79093] [PMID: 22096313]
[59]
Batra, P.; Sharma, A.K. Anti-cancer potential of flavonoids: Recent trends and future perspectives. 3 Biotech, 2013, 3(6), 439-459.
[60]
Barrera, G. Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol., 2012, 2012Article ID. 137289
[http://dx.doi.org/10.5402/2012/137289]
[61]
Chikkula, K.V.; Raja, S. Isoxazole–a potent pharmacophore. Int. J. Pharm. Pharm. Sci., 2017, 9(7), 13-24.
[http://dx.doi.org/10.22159/ijpps.2017.v9i7.19097]
[62]
Wang, D.; Dubois, R.N. The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene, 2010, 29(6), 781-788.
[http://dx.doi.org/10.1038/onc.2009.421] [PMID: 19946329]
[63]
Parker, W.B. Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem. Rev., 2009, 109(7), 2880-2893.
[http://dx.doi.org/10.1021/cr900028p] [PMID: 19476376]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy