Characterization of the Saffron Derivative Crocetin as an Inhibitor of Human Lactate Dehydrogenase 5 in the Antiglycolytic Approach against Cancer

Journal of Agricultural and Food Chemistry

Volumn 65, Issue 28, 2017, Pages 5639-5649

  Granchi, Carlotta ^a   Fortunato, Serena ^a   Meini, Serena ^a   Rizzolio, Flavio ^c   Caligiuri, Isabella ^d   Tuccinardi, Tiziano ^a   Lee, Hyang Yeon ^b   Hergenrother, Paul J ^b   Minutolo, Filippo ^a  

^a UNIVERSITY OF PISA   (Italy)

^b UNIVERSITY OF ILLINOIS AT URBANA CHAMPAIGN   (United States)

^c CA' FOSCARI UNIVERSITY OF VENICE   (Italy)

^d CENTRO DI RIFERIMENTO ONCOLOGICO   (Italy)

Author keywords

cancer; crocetin; glycolysis; lactate dehydrogenase; saffron

Indexed keywords

CELL CULTURE; FOOD ADDITIVES;

CANCER; CROCETIN; GLYCOLYSIS; LACTATE DEHYDROGENASE; SAFFRON;

DISEASES;

CAROTENOID; CROCETIN; ENZYME INHIBITOR; ISOENZYME; LACTATE DEHYDROGENASE; LACTATE DEHYDROGENASE 5; LACTIC ACID;

ANTAGONISTS AND INHIBITORS; CELL LINE; CHEMICAL STRUCTURE; CHEMISTRY; CROCUS; ENZYMOLOGY; FLOWER; GENETICS; GLYCOLYSIS; HUMAN; METABOLISM; MOLECULAR DOCKING; NEOPLASMS;

CAROTENOIDS; CELL LINE; CROCUS; ENZYME INHIBITORS; FLOWERS; GLYCOLYSIS; HUMANS; ISOENZYMES; L-LACTATE DEHYDROGENASE; LACTIC ACID; MOLECULAR DOCKING SIMULATION; MOLECULAR STRUCTURE; NEOPLASMS;

EID: 85025139363     PISSN: 00218561     EISSN: 15205118     Source Type: Journal    
DOI: 10.1021/acs.jafc.7b01668     Document Type: Article

References (50)

1. Warburg, O. On the origin of cancer cells Science 1956, 123, 309-314 10.1126/science.123.3191.309
2. Granchi, C.; Minutolo, F. Anticancer agents that counteract tumor glycolysis ChemMedChem 2012, 7, 1318-1350 10.1002/cmdc.201200176
3. Granchi, C.; Fancelli, D.; Minutolo, F. An update on therapeutic opportunities offered by cancer glycolytic metabolism Bioorg. Med. Chem. Lett. 2014, 24, 4915-4925 10.1016/j.bmcl.2014.09.041
4. Kanno, T.; Sudo, K.; Maekawa, M.; Nishimura, Y.; Ukita, M.; Fukutake, K. Lactate dehydrogenase M-subunit deficiency: a new type of hereditary exertional myopathy Clin. Chim. Acta 1988, 173, 89-98 10.1016/0009-8981(88)90359-2
5. Fantin, V. R.; St-Pierre, J.; Leder, P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance Cancer Cell 2006, 9, 425-434 10.1016/j.ccr.2006.04.023
6. Granchi, C.; Paterni, I.; Rani, R.; Minutolo, F. Small-molecule inhibitors of human LDH5 Future Med. Chem. 2013, 5, 1967-1991 10.4155/fmc.13.151
7. Gomez, M. S.; Piper, R. C.; Hunsaker, L. A.; Royer, R. E.; Deck, L. M.; Makler, M. T.; Vander Jagt, D. L. Substrate and cofactor specificity and selective inhibition of lactate dehydrogenase from the malarial parasite P. falciparum Mol. Biochem. Parasitol. 1997, 90, 235-246 10.1016/S0166-6851(97)00140-0
8. Wang, Z.; Wang, D.; Han, S.; Wang, N.; Mo, F.; Loo, T. Y.; Shen, J.; Huang, H.; Chen, J. Bioactivity-guided identification and cell signaling technology to delineate the lactate dehydrogenase A inhibition effects of Spatholobus suberectus on breast cancer PLoS One 2013, 8, e56631 10.1371/journal.pone.0056631
9. Arora, R.; Schmitt, D.; Karanam, B.; Tan, M.; Yates, C.; Dean-Colomb, W. Inhibition of the Warburg effect with a natural compound reveals a novel measurement for determining the metastatic potential of breast cancers Oncotarget 2015, 6, 662-678 10.18632/oncotarget.2689
10. Ramanathan, R.; Mancini, R. A.; Suman, S. P.; Beach, C. M. Covalent binding of 4-hydroxy-2-nonenal to lactate dehydrogenase decreases NADH formation and metmyoglobin reducing activity J. Agric. Food Chem. 2014, 62, 2112-2117 10.1021/jf404900y
11. Deiab, S.; Mazzio, E.; Eyunni, S.; McTier, O.; Mateeva, N.; Elshami, F.; Soliman, K. F. 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells Evid. Based Complement. Alternat. Med. 2015, 2015, 276946 10.1155/2015/276946
12. Manerba, M.; Vettraino, M.; Fiume, L.; Di Stefano, G.; Sartini, A.; Giacomini, E.; Buonfiglio, R.; Roberti, M.; Recanatini, M. Galloflavin (CAS 568-80-9): a novel inhibitor of lactate dehydrogenase ChemMedChem 2012, 7, 311-317 10.1002/cmdc.201100471
13. Bader, A.; Tuccinardi, T.; Granchi, C.; Martinelli, A.; Macchia, M.; Minutolo, F.; De Tommasi, N.; Braca, A. Phenylpropanoids and flavonoids from Phlomis kurdica as inhibitors of human lactate dehydrogenase Phytochemistry 2015, 116, 262-268 10.1016/j.phytochem.2015.03.007
14. Deiab, S.; Mazzio, E.; Messeha, S.; Mack, N.; Soliman, K. F. High-Throughput Screening to Identify Plant Derived Human LDH-A Inhibitors Eur. J. Med. Plants 2013, 3, 603-615 10.9734/EJMP/2013/5995
15. Bathaie, S. Z.; Mousavi, S. Z. New applications and mechanisms of action of saffron and its important ingredients Crit. Rev. Food Sci. Nutr. 2010, 50, 761-786 10.1080/10408390902773003
16. Christodoulou, E.; Kadoglou, N. P.; Kostomitsopoulos, N.; Valsami, G. Saffron: a natural product with potential pharmaceutical applications J. Pharm. Pharmacol. 2015, 67, 1634-1649 10.1111/jphp.12456
17. Geromichalos, G. D.; Lamari, F. N.; Papandreou, M. A.; Trafalis, D. T.; Margarity, M.; Papageorgiou, A.; Sinakos, Z. Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies J. Agric. Food Chem. 2012, 60, 6131-618 10.1021/jf300589c
18. Ahrazem, O.; Rubio-Moraga, A.; Nebauer, S. G.; Molina, R. V.; Gómez-Gómez, L. Saffron: Its Phytochemistry, Developmental Processes, and Biotechnological Prospects J. Agric. Food Chem. 2015, 63, 8751-8764 10.1021/acs.jafc.5b03194
19. Cossignani, L.; Urbani, E.; Simonetti, M. S.; Maurizi, A.; Chiesi, C.; Blasi, F. Characterisation of secondary metabolites in saffron from central Italy (Cascia, Umbria) Food Chem. 2014, 143, 446-451 10.1016/j.foodchem.2013.08.020
20. Nescatelli, R.; Carradori, S.; Marini, F.; Caponigro, V.; Bucci, R.; De Monte, C.; Mollica, A.; Mannina, L.; Ceruso, M.; Supuran, C. T.; Secci, D. Geographical characterization by MAE-HPLC and NIR methodologies and carbonic anhydrase inhibition of Saffron components Food Chem. 2017, 221, 855-863 10.1016/j.foodchem.2016.11.086
21. Lu, P.; Lin, H.; Gu, Y.; Li, L.; Guo, H.; Wang, F.; Qiu, X. Antitumor effects of crocin on human breast cancer cells Int. J. Clin. Exp. Med. 2015, 8, 20316-20322
22. Chen, S.; Zhao, S.; Wang, X.; Zhang, L.; Jiang, E.; Gu, Y.; Shangguan, A. J.; Zhao, H.; Lv, T.; Yu, Z. Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells Transl. Lung Cancer Res. 2015, 4, 775-783 10.3978/j.issn.2218-6751.2015.11.03
23. Xia, D. Ovarian cancer HO-8910 cell apoptosis induced by crocin in vitro Nat. Prod. Commun. 2015, 10, 249-252
24. D'Alessandro, A. M.; Mancini, A.; Lizzi, A. R.; De Simone, A.; Marroccella, C. E.; Gravina, G. L.; Tatone, C.; Festuccia, C. Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer Nutr. Cancer 2013, 65, 930-942 10.1080/01635581.2013.767368
25. Gutheil, W. G.; Reed, G.; Ray, A.; Anant, S.; Dhar, A. Crocetin: an agent derived from saffron for prevention and therapy for cancer Curr. Pharm. Biotechnol. 2012, 13, 173-179 10.2174/138920112798868566
26. Li, S.; Jiang, S.; Jiang, W.; Zhou, Y.; Shen, X. Y.; Luo, T.; Kong, L. P.; Wang, H. Q. Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells Oncol. Lett. 2015, 9, 1254-1260 10.3892/ol.2015.2869
27. Festuccia, C.; Mancini, A.; Gravina, G. L.; Scarsella, L.; Llorens, S.; Alonso, G. L.; Tatone, C.; Di Cesare, E.; Jannini, E. A.; Lenzi, A.; D'Alessandro, A. M.; Carmona, M. Antitumor effects of saffron-derived carotenoids in prostate cancer cell models BioMed Res. Int. 2014, 2014, 135048 10.1155/2014/135048
28. He, K.; Si, P.; Wang, H.; Tahir, U.; Chen, K.; Xiao, J.; Duan, X.; Huang, R.; Xiang, G. Crocetin induces apoptosis of BGC-823 human gastric cancer cells Mol. Med. Rep. 2014, 9, 521-526 10.3892/mmr.2013.1851
29. Bathaie, S. Z.; Hoshyar, R.; Miri, H.; Sadeghizadeh, M. Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer Biochem. Cell Biol. 2013, 91, 397-403 10.1139/bcb-2013-0014
30. Asai, A.; Nakano, T.; Takahashi, M.; Nagao, A. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice J. Agric. Food Chem. 2005, 53, 7302-7306 10.1021/jf0509355
31. Caballero-Ortega, H.; Pereda-Miranda, R.; Abdullaev, F. I. HPLC quantification of major active components from 11 different saffron (Crocus sativus L.) sources Food Chem. 2007, 100, 1126-1131 10.1016/j.foodchem.2005.11.020
32. Umigai, N.; Murakami, K.; Ulit, M.; Antonio, L.; Shirotori, M.; Morikawa, H.; Nakano, T. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration Phytomedicine 2011, 18, 575-578 10.1016/j.phymed.2010.10.019
33. Kim, S. H.; Lee, J. M.; Kim, S. C.; Park, C. B.; Lee, P. C. Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines Biochem. Cell Biol. 2014, 92, 105-111 10.1139/bcb-2013-0091
34. Fauber, B. P.; Dragovich, P. S.; Chen, J.; Corson, L. B.; Ding, C. Z.; Eigenbrot, C.; Giannetti, A. M.; Hunsaker, T.; Labadie, S.; Liu, Y.; Malek, S.; Peterson, D.; Pitts, K.; Sideris, S.; Ultsch, M.; VanderPorten, E.; Wang, J.; Wei, B.; Yen, I.; Yue, Q. Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate dehydrogenase Bioorg. Med. Chem. Lett. 2013, 23, 5533-5539 10.1016/j.bmcl.2013.08.060
35. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E. The Protein Data Bank Nucleic Acids Res. 2000, 28, 235-242 10.1093/nar/28.1.235
36. Morris, G. M.; Huey, R.; Lindstrom, W.; Sanner, M. F.; Belew, R. K.; Goodsell, D. S.; Olson, A. J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility J. Comput. Chem. 2009, 30, 2785-2791 10.1002/jcc.21256
37. Case, D. A.; Berryman, J. T.; Betz, R. M.; Cerutti, D. S.; Cheatham, T. E., III; Darden, T. A.; Duke, R. E.; Giese, T. J.; Gohlke, H.; Goetz, A. W.; Homeyer, N.; Izadi, S.; Janowski, P.; Kaus, J.; Kovalenko, A.; Lee, T. S.; LeGrand, S.; Li, P.; Luchko, T.; Luo, R.; Madej, B.; Merz, K. M.; Monard, G.; Needham, P.; Nguyen, H.; Nguyen, H. T.; Omelyan, I.; Onufriev, A.; Roe, D. R.; Roitberg, A.; Salomon-Ferrer, R.; Simmerling, C. L.; Smith, W.; Swails, J.; Walker, R. C.; Wang, J.; Wolf, R. M.; Wu, X.; York, D. M.; Kollman, P. A. AMBER, version 14; University of California: San Francisco, CA, 2015.
38. York, D. M.; Darden, T. A.; Pedersen, L. G. The Effect of Long-Range Electrostatic Interactions in Simulations of Macromolecular Crystals-a Comparison of the Ewald and Truncated List Methods J. Chem. Phys. 1993, 99, 8345-8348 10.1063/1.465608
39. Roe, D. R.; Cheatham, T. E., 3rd. PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data J. Chem. Theory Comput. 2013, 9, 3084-3095 10.1021/ct400341p
40. Gainer, J. L.; Grabiak, R. C. Bipolar trans carotenoid salts and their uses. U.S. Patent Application 2004116729, June 17, 2004.
41. Van Calsteren, M.-R.; Bissonnette, M. C.; Cormier, F.; Dufresne, C.; Ichi, T.; LeBlanc, J. C. Y.; Perreault, D.; Roewer, I. Spectroscopic Characterization of Crocetin Derivatives from Crocus sativus and Gardenia jasminoides J. Agric. Food Chem. 1997, 45, 1055-1061 10.1021/jf9603487
42. Vichai, V.; Kirtikara, K. Sulforhodamine B colorimetric assay for cytotoxicity screening Nat. Protoc. 2006, 1, 1112-1116 10.1038/nprot.2006.179
43. Granchi, C.; Calvaresi, E. C.; Tuccinardi, T.; Paterni, I.; Macchia, M.; Martinelli, A.; Hergenrother, P. J.; Minutolo, F. Assessing the differential action on cancer cells of LDH-A inhibitors based on the N-hydroxyindole-2-carboxylate (NHI) and malonic (Mal) scaffolds Org. Biomol. Chem. 2013, 11, 6588-6596 10.1039/c3ob40870a
44. Calvaresi, E. C.; Granchi, C.; Tuccinardi, T.; Di Bussolo, V.; Huigens, R. W., 3rd; Lee, H. Y.; Palchaudhuri, R.; Macchia, M.; Martinelli, A.; Minutolo, F.; Hergenrother, P. J. Dual targeting of the Warburg effect with a glucose-conjugated lactate dehydrogenase inhibitor ChemBioChem 2013, 14, 2263-2267 10.1002/cbic.201300562
45. Di Bussolo, V.; Calvaresi, E. C.; Granchi, C.; Del Bino, L.; Frau, I.; Lang, M. C.; Tuccinardi, T.; Macchia, M.; Martinelli, A.; Hergenrother, P. J.; Minutolo, F. Synthesis and biological evaluation of non-glucose glycoconjugated N-hydroyxindole class LDH inhibitors as anticancer agents RSC Adv. 2015, 5, 19944-19954 10.1039/C5RA00946D
46. Kollman, P. A.; Massova, I.; Reyes, C.; Kuhn, B.; Huo, S.; Chong, L.; Lee, M.; Lee, T.; Duan, Y.; Wang, W.; Donini, O.; Cieplak, P.; Srinivasan, J.; Case, D. A.; Cheatham, T. E., 3rd. Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models Acc. Chem. Res. 2000, 33, 889-897 10.1021/ar000033j
47. Tuccinardi, T.; Granchi, C.; Iegre, J.; Paterni, I.; Bertini, S.; Macchia, M.; Martinelli, A.; Qian, Y.; Chen, X.; Minutolo, F. Oxime-based inhibitors of glucose transporter 1 displaying antiproliferative effects in cancer cells Bioorg. Med. Chem. Lett. 2013, 23, 6923-6927 10.1016/j.bmcl.2013.09.037
48. Tuccinardi, T.; Manetti, F.; Schenone, S.; Martinelli, A.; Botta, M. Construction and validation of a RET TK catalytic domain by homology modeling J. Chem. Inf. Model. 2007, 47, 644-655 10.1021/ci6004383
49. Abdullaev, F.; Riveron-Negrete, L.; Caballero-Ortega, H.; Hernández, J. M.; Perez-Lopez, I.; Pereda-Miranda, R.; Espinosa-Aguirre, J. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.) Toxicol. In Vitro 2003, 17, 731-736 10.1016/S0887-2333(03)00098-5
50. Modaghegh, M.-H.; Shahabian, M.; Esmaeili, H.-A.; Rajbai, O.; Hosseinzadeh, H. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers Phytomedicine 2008, 15, 1032-1037 10.1016/j.phymed.2008.06.003