Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches

Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HE...

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Autores:
Trujillo, Lina
Bedoya, Janeth
Cortés, Natalie
Osorio, Edison H.
Gallego, Juan-Carlos
Leiva, Hawer
Castro, Dagoberto
Tipo de recurso:
Article of journal
Fecha de publicación:
2023
Institución:
Universidad de Ibagué
Repositorio:
Repositorio Universidad de Ibagué
Idioma:
eng
OAI Identifier:
oai:repositorio.unibague.edu.co:20.500.12313/3839
Acceso en línea:
https://hdl.handle.net/20.500.12313/3839
Palabra clave:
Amaryllidaceae alkaloids
Cancer
Cytotoxic activity
In silico assays
Rights
openAccess
License
http://purl.org/coar/access_right/c_abf2
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oai_identifier_str oai:repositorio.unibague.edu.co:20.500.12313/3839
network_acronym_str UNIBAGUE2
network_name_str Repositorio Universidad de Ibagué
repository_id_str
dc.title.eng.fl_str_mv Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
title Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
spellingShingle Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
Amaryllidaceae alkaloids
Cancer
Cytotoxic activity
In silico assays
title_short Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
title_full Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
title_fullStr Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
title_full_unstemmed Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
title_sort Cytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approaches
dc.creator.fl_str_mv Trujillo, Lina
Bedoya, Janeth
Cortés, Natalie
Osorio, Edison H.
Gallego, Juan-Carlos
Leiva, Hawer
Castro, Dagoberto
dc.contributor.author.none.fl_str_mv Trujillo, Lina
Bedoya, Janeth
Cortés, Natalie
Osorio, Edison H.
Gallego, Juan-Carlos
Leiva, Hawer
Castro, Dagoberto
dc.subject.proposal.eng.fl_str_mv Amaryllidaceae alkaloids
Cancer
Cytotoxic activity
In silico assays
topic Amaryllidaceae alkaloids
Cancer
Cytotoxic activity
In silico assays
description Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatment
publishDate 2023
dc.date.accessioned.none.fl_str_mv 2023-10-17T20:51:21Z
dc.date.available.none.fl_str_mv 2023-10-17T20:51:21Z
dc.date.issued.none.fl_str_mv 2023-03-13
dc.type.none.fl_str_mv Artículo de revista
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dc.type.content.none.fl_str_mv Text
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dc.identifier.citation.none.fl_str_mv Trujillo, L.; Bedoya, J.; Cortés, N.; Osorio, E.H.; Gallego, J.-C.; Leiva, H.; Castro, D.; Osorio, E. Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches. Molecules 2023, 28, 2601. https://doi.org/10.3390/ molecules28062601
dc.identifier.issn.none.fl_str_mv 14203049
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12313/3839
identifier_str_mv Trujillo, L.; Bedoya, J.; Cortés, N.; Osorio, E.H.; Gallego, J.-C.; Leiva, H.; Castro, D.; Osorio, E. Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches. Molecules 2023, 28, 2601. https://doi.org/10.3390/ molecules28062601
14203049
url https://hdl.handle.net/20.500.12313/3839
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.citationendpage.none.fl_str_mv 18
dc.relation.citationissue.none.fl_str_mv 2601
dc.relation.citationstartpage.none.fl_str_mv 1
dc.relation.citationvolume.none.fl_str_mv 28
dc.relation.ispartofjournal.none.fl_str_mv Molecules
dc.relation.references.none.fl_str_mv Ferlay, J.; Colombet, M.; Soerjomataram, I.; Parkin, D.M.; Pineros, M.; Znaor, A.; Bray, F. Cancer statistics for the year 2020: An overview. Int. J. Cancer 2021, 149, 778–789
Arnold, M.; Morgan, E.; Rumgay, H.; Mafra, A.; Singh, D.; Laversanne, M.; Vignat, J.; Gralow, J.R.; Cardoso, F.; Siesling, S.; et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 2022, 66, 15–23
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249
Heer, E.; Harper, A.; Escandor, N.; Sung, H.; McCormack, V.; Fidler-Benaoudia, M.M. Global burden and trends in premenopausal and postmenopausal breast cancer: A population-based study. Lancet Glob. Health 2020, 8, e1027–e1037
Gallagher, B.D.T.; Coughlin, E.C.; Nair-Shalliker, V.; McCaffery, K.; Smith, D.P. Socioeconomic differences in prostate cancer treatment: A systematic review and meta-analysis. Cancer Epidemiol. 2022, 79, 102164
López, M.J.; Carbajal, J.; Alfaro, A.L.; Saravia, L.G.; Zanabria, E.D.; Araujo, J.M.; Quispe, L.; Vizcarra, K.A.; Buleje, J.L.; Choo, C.E.; et al. Characteristics of gastric cancer around the World. Crit. Rev. Oncol. Hematol. 2022, 181, 103841
Nyame, Y.A.; Cooperberg, M.R.; Cumberbatch, M.G.; Eggener, S.E.; Etzioni, R.; Gomez, S.L.; Haiman, C.; Huang, F.; Lee, C.T.; Litwin, M.S.; et al. Deconstructing, addressing, and eliminating racial and ethnic inequities in prostate cancer care. Eur. Urol. 2022, 82, 341–351
Bray, F.; Laversanne, M.; Weiderpass, E.; Soerjomataram, I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 2021, 127, 3029–3030
Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics. CA Cancer J. Clin. 2022, 72, 7–33
Miller, K.D.; Nogueira, L.; Mariotto, A.B.; Rowland, J.H.; Yabroff, K.R.; Alfano, C.M.; Jemal, A.; Kramer, J.L.; Siegel, R.L. Cancer treatment and survivorship statistics, 2019. CA Cancer J. Clin. 2019, 69, 363–385
Koskas, M.; Amant, F.; Mirza, M.R.; Creutzberg, C.L. Cancer of the corpus uteri: 2021 update. Int. J. Gynecol. Obstet. 2021, 155, 45–60
Patel, A.; Iyer, P.; Matsuzaki, S.; Matsuo, K.; Sood, A.K.; Fleming, N.D. Emerging trends in neoadjuvant chemotherapy for ovarian cancer. Cancers 2021, 13, 626
Rangarajan, K.; Pucher, P.H.; Armstrong, T.; Bateman, A.; Hamady, Z. Systemic neoadjuvant chemotherapy in modern pancreatic cancer treatment: A systematic review and meta-analysis. Ann. R. Coll. Surg. Engl. 2019, 101, 453–462
Groenewold, M.D.; Olthof, C.G.; Bosch, D.J. Anaesthesia after neoadjuvant chemotherapy, immunotherapy or radiotherapy. BJA Educ. 2022, 22, 12–19
Wang, Z.; Mo, H.; He, Z.; Chen, A.; Cheng, P. Extracellular vesicles as an emerging drug delivery system for cancer treatment: Current strategies and recent advances. Biomed. Pharmacother. 2022, 153, 113480
Anand, U.; Dey, A.; Singh, A.K.; Sanyal, R.; Mishra, A.; Pandey, D.K.; De Falco, V.; Upadhyay, A.; Kandimalla, R.; Chaudhary, A.; et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2023; in press
Nguyen, L.T.S.; Jacob, M.A.C.; Parajón, E.; Robinson, D.N. Cancer as a biophysical disease: Targeting the mechanical-adaptability program. Biophys. J. 2022, 121, 3573–3585
Babar, Q.; Saeed, A.; Tabish, T.A.; Pricl, S.; Townley, H.; Thorat, N. Novel epigenetic therapeutic strategies and targets in cancer. Biochim. Biophys. Acta Mol. Basis Dis. 2022, 1868, 166552
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770–803
Lu, J.J.; Wang, Y.T. Identification of anti-cancer compounds from natural products. Chin. J. Nat. Med. 2020, 18, 481–482
Qiu, S.; Sun, H.; Zhang, A.H.; Xu, H.Y.; Yan, G.L.; Han, Y.; Wang, X.J. Natural alkaloids: Basic aspects, biological roles, and future perspectives. Chin. J. Nat. Med. 2014, 12, 401–406
Howes, M.J.R. The evolution of anticancer drug discovery from plants. Lancet Oncol. 2018, 19, 293–294
Roussi, F.; Gueritte, F.; Fahy, J. The Vinca alkaloids. In Anticancer Agents from Natural Products, 2nd ed.; Cragg, G.M., Kingston, D.G.I., Newman, D.J., Eds.; CRC/Taylor & Francis: Boca Raton, FL, USA, 2012; pp. 177–198
Cragg, G.M.; Pezzuto, J.M. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med. Princ. Pract. 2016, 25, 41–59
Nair, J.J.; Van Staden, J.; Bastida, J. Cytotoxic alkaloid constituents of the Amaryllidaceae. Stud. Nat. Prod. Chem. 2016, 49, 107–156
Berkov, S.; Osorio, E.; Viladomat, F.; Bastida, J. Chemodiversity, chemotaxonomy and chemoecology of Amaryllidaceae alkaloids. In Alkaloids: Chemistry and Biology; Knölker, H.-J., Ed.; Elsevier Inc.: Amsterdam, The Netherlands, 2020; Volume 83, pp. 113–185
Kornienko, A.; Evidente, A. Chemistry, biology, and medicinal potential of narciclasine and its congeners. Chem. Rev. 2008, 108, 1982–2014
Nair, J.J.; Bastida, J.; van Staden, J. In vivo cytotoxicity studies of Amaryllidaceae alkaloids. Nat. Prod. Commun. 2016, 11, 121–132
Botteon, C.E.A.; Silva, L.B.; Ccana-Ccapatinta, G.V.; Silva, T.S.; Ambrosio, S.R.; Veneziani, R.C.S.; Bastos, J.K.; Marcato, P.D. Biosynthesis and characterization of gold nanoparticles using Brazilian red propolis and evaluation of its antimicrobial and anticancer activities. Sci. Rep. 2021, 11, 1974
Omoruyi, S.I.; Kangwa, T.S.; Ibrakaw, A.S.; Cupido, C.N.; Marnewick, J.L.; Ekpo, O.E.; Hussein, A.A. Cytotoxic activities of selected plants of the family Amaryllidaceae on brain tumour cell lines. S. Afr. J Bot. 2021, 136, 118–125
Silverstone, P. Los Muertos Vivientes: La Historia Natural de Cuatro Lirios Amazónicos Del Suroccidente de Colombia; Editorial Universidad del Valle: Santiago de Cali, Colombia, 2011; p. 24
Fennell, C.; Crouch, N.; van Staden, J. Micropropagation of the River Lily, Crinum variabile (Amaryllidaceae). S. Afr. J. Bot. 2001, 67, 74–77
Guerrero-Valencia, F.A.; Rodríguez-de la O, J.L.; De, J.; Juárez-Hernández, M.; Ayala-Arreola, J.; Ramírez-González, G. Micropropagation of Amazon Lily (Eucharis Grandiflora Planch. & Linden) Through Direct Organogenesis. Polibotánica 2021, 51, 141–153
Akinyele, S.T.; Elusiyan, C.A.; Omisore, N.O.; Adewunmi, C.O. Antimalarial activities and alkaloids from Crinum jagus (Thomps) DANDY. J. Ethnopharmacol. 2022, 296, 115359
Cortes, N.; Posada-Duque, R.A.; Alvarez, R.; Alzate, F.; Berkov, S.; Cardona-Gómez, G.P.; Osorio, E. Neuroprotective activity and acetylcholinesterase inhibition of five Amaryllidaceae species: A comparative study. Life Sci. 2015, 122, 42–50
Cortes, N.; Castañeda, C.; Osorio, E.H.; Cardona-Gomez, G.P.; Osorio, E. Amaryllidaceae alkaloids as agents with protective effects against oxidative neural cell injury. Life Sci. 2018, 203, 54–65
Ka, S.; Masi, M.; Merindol, N.; Di Lecce, R.; Plourde, M.B.; Seck, M.; Górecki, M.; Pescitelli, G.; Desgagne-Penix, I.; Evidente, A. Gigantelline, gigantellinine and gigancrinine, cherylline- and crinine-type alkaloids isolated from Crinum jagus with anti-acetylcholinesterase activity. Phytochemistry 2020, 175, 112390
Cortes, N.; Posada-Duque, R.; Cardona-Gómez, G.P.; Bastida, J.; Osorio, E. Chapter 13—Amaryllidaceae alkaloids and neuronal cell protection. In Pathology, Oxidative Stress and Dietary Antioxidants; Preedy, V.R., Ed.; Academic Press: London, UK, 2020; pp. 135–144
Trujillo-Chacón, L.M.; Alarcón-Enos, J.E.; Céspedes-Acuña, C.L.; Bustamante, L.; Baeza, M.; López, M.G.; Fernández-Mendívil, C.; Cabezas, F.; Pastene-Navarrete, E.R. Neuroprotective activity of isoquinoline alkaloids from of Chilean Amaryllidaceae plants against oxidative stress-induced cytotoxicity on human neuroblastoma SH-SY5Y cells and mouse hippocampal slice culture. Food Chem. Toxicol. 2019, 132, 110665
Cortes, N.; Sabogal-Guaqueta, A.M.; Cardona-Gomez, G.P.; Osorio, E. Neuroprotection and improvement of the histopathological and behavioral impairments in a murine Alzheimer’s model treated with Zephyranthes carinata alkaloids. Biomed. Pharmacother. 2019, 110, 482–492
Rojas-Vera, J.; Buitrago-Díaz, A.A.; Possamai, L.M.; Timmers, L.F.S.M.; Tallini, L.R.; Bastida, J. Alkaloid profile and cholinesterase inhibition activity of five species of Amaryllidaceae family collected from Mérida state-Venezuela. S. Afr. J. Bot. 2021, 136, 126–136
Sierra, K.; de Andrade, J.P.; Tallini, L.R.; Osorio, E.H.; Yañéz, O.; Osorio, M.I.; Oleas, N.H.; García-Beltrán, O.; Borges, W.; Bastida, J.; et al. In vitro and in silico analysis of galanthine from Zephyranthes carinata as an inhibitor of acetylcholinesterase. Biomed. Pharmacother. 2022, 150, 113016
Zhong, L.; Li, Y.; Xiong, L. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Sig. Transduct. Target Ther. 2021, 6, 201
Nair, J.J.; Bastida, J.; Viladomat, F.; van Staden, J. Cytotoxic agents of the crinane series of Amaryllidaceae alkaloids. Nat. Prod. Commun. 2012, 7, 1677–1688
Nair, J.J.; van Staden, J. Cytotoxicity studies of lycorine alkaloids of the Amaryllidaceae. Nat. Prod. Commun. 2014, 9, 1193–1210
D’Aguanno, S.; Del Bufalo, D. Inhibition of anti-apoptotic Bcl-2 proteins in preclinical and clinical studies: Current Overview in Cancer. Cells 2020, 9, 1287
Li, R.; Mei, S.; Ding, Q.; Wang, Q.; Yu, L.; Zi, F. A pan-cancer analysis of the role of hexokinase II (HK2) in human tumors. Sci. Rep. 2022, 12, 18807
Basu, A. The interplay between apoptosis and cellular senescence: Bcl-2 family proteins as targets for cancer therapy. Pharmacol. Ther. 2022, 230, 107943
Gryko, M.; Pryczynicz, A.; Guzińska-Ustymowicz, K.; Kamocki, Z.; Zaręba, K.; Kemona, A.; Kędra, B. Immunohistochemical assessment of apoptosis-associated proteins: p53, Bcl-xL, Bax and Bak in gastric cancer cells in correlation with clinical and pathomorphological factors. Adv. Med. Sci. 2012, 57, 77–83
Yuan, L.W.; Yamashita, H.; Seto, Y. Glucose metabolism in gastric cancer: The cutting-edge. World J. Gastroenterol. 2016, 22, 2046–2059
Chen, L.; Guo, L.; Sun, Z.; Yang, G.; Guo, J.; Chen, K.; Xiao, R.; Yang, X.; Sheng, L. Monoamine oxidase a is a major mediator of mitochondrial homeostasis and glycolysis in gastric cancer progression. Cancer Manag. Res. 2020, 12, 8023–8035
Nguyen, M.; Marcellus, R.C.; Roulston, A.; Watson, M.; Serfass, L.; Murthy Madiraju, S.R.; Goulet, D.; Viallet, J.; Bélec, L.; Billot, X.; et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl. Acad. Sci. USA 2007, 104, 19512–19517
Rahmani, M.; Aust, M.M.; Attkisson, E.; Williams, D.C.; Ferreira-Gonzalez, A.; Grant, S. Inhibition of Bcl-2 antiapoptotic members by obatoclax potently enhances sorafenib-induced apoptosis in human myeloid leukemia cells through a Bim-dependent process. Blood 2012, 119, 6089–6098
Sebola, T.E.; Uche-Okereafor, N.C.; Mekuto, L.; Makatini, M.M.; Green, E.; Mavumengwana, V. Antibacterial and anticancer activity and untargeted secondary metabolite profiling of crude bacterial endophyte extracts from Crinum macowanii Baker Leaves. Int. J. Microbiol. 2020, 2020, 8839490
Nair, J.J.; van Staden, J. Cytotoxic tazettine alkaloids of the plant family Amaryllidaceae. S. Afr. J. Bot. 2021, 136, 147–156
Rice, L.J.; Finnie, J.F.; Van Staden, J. In vitro bulblet production of Brunsvigia undulata from twin-scales. S. Afr. J. Bot. 2011, 77, 305–312
Murashige, T.; Skoog, F. A revised medium for rapid growth and bio assays with tobacco tissue cultures. Physiol. Plant. 1962, 15, 473–497
Dartier, J.; Lemaitre, E.; Chourpa, I.; Goupille, C.; Servais, S.; Chevalier, S.; Mahéo, K.; Dumas, J.-F. ATP-dependent activity and mitochondrial localization of drug efflux pumps in doxorubicin-resistant breast cancer cells. Biochim. Biophys. Acta 2017, 5, 1075–1084
Lee, Y.J.; Park, K.S.; Lee, S.H. Curcumin targets both apoptosis and necroptosis in acidity-tolerant prostate carcinoma cells. BioMed Res. Int. 2021, 2021, 8859181
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
Porter, J.; Payne, A.; de Candole, B.; Ford, D.; Hutchinson, B.; Trevitt, G.; Turner, J.; Edwards, C.; Watkins, C.; Whitcombe, I.; et al. Crystal Structure of Chimaeric Bcl2-xL and Phenyl Tetrahydroisoquinoline Amide Complex. Protein Data Bank 2008, 2W3L
Czabotar, P.E.; Lee, E.F.; Smith, B.J.; Deshayes, K.; Zobel, K.; Fairlie, W.D.; Colman, P.M. Crystal structure of Bcl-xL in complex with ABT-737. Protein Data Bank 2007, 2YXJ
Dutta, S.; Fire, E.; Grant, R.A.; Sauer, R.T.; Keating, A.E. MCL-1 complex with MCL-1-specific selected peptide. Protein Data Bank 2017, 3KZ0
Lin, H.; Zeng, J.; Xie, R.; Schulz, M.J.; Tedesco, R.; Qu, J.; Erhard, K.F.; Mack, J.F.; Raha, K.; Rendina, A.R.; et al. Discovery of a novel 2,6-disubstituted glucosamine series of potent and selective Hexokinase 2 Inhibitors. ACS Med. Chem. Lett. 2016, 7, 217–222
Sathishkumar, N.; Sathiyamoorthy, S.; Ramya, M.; Yang, D.-U.; Lee, H.N.; Yang, D.-C. Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng. J. Enzyme Inhib. Med. Chem. 2012, 27, 685–692
Swargiary, G.; Mani, S. Molecular docking and simulation studies of phytocompounds derived from Centella asiatica and Andrographis paniculata against hexokinase II as mitocan agents. Mitochondrion 2021, 61, 138–146
Kazi, A.; Sun, J.; Doi, K.; Sung, S.S.; Takahashi, Y.; Yin, H.; Rodriguez, J.M.; Becerril, J.; Berndt, N.; Hamilton, A.D.; et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J. Biol. Chem. 2011, 286, 9382–9392
Dalafave, D.S.; Prisco, G. Inhibition of antiapoptotic BCL-XL, BCL-2, and MCL-1 proteins by small molecule mimetics. Cancer Inform. 2010, 9, CIN.S5065-177
Khan, A.; Mohammad, T.; Shamsi, A.; Hussain, A.; Alajmi, M.F.; Husain, S.A.; Iqbal, M.A.; Hassan, M.I. Identification of plant-based hexokinase 2 inhibitors: Combined molecular docking and dynamics simulation studies. J. Biomol. Struct. Dyn. 2022, 40, 10319–10331
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998, 19, 1639–1662
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spelling Trujillo, Linadb35c764-d73e-4393-a97f-e865a3d81421-1Bedoya, Janeth82bfd55c-e000-4b86-b5e0-e6d35cc01c8a-1Cortés, Natalie16e73ae2-5c91-425c-9ce1-5026766280f8-1Osorio, Edison H.087e0c0b-d49f-4915-b7fa-272d785c30af-1Gallego, Juan-Carlos0683bcdc-78df-419a-ba22-20fdc9838eeb-1Leiva, Hawer5f850761-9909-4bb3-8838-980981259973-1Castro, Dagoberto58722899-215a-4344-a1ba-8b28813c3ec1-12023-10-17T20:51:21Z2023-10-17T20:51:21Z2023-03-13Cancer is a major cause of death and an impediment to increasing life expectancy worldwide. With the aim of finding new molecules for chemotherapeutic treatment of epidemiological relevance, ten alkaloid fractions from Amaryllidaceae species were tested against six cancer cell lines (AGS, BT-549, HEC-1B, MCF-7, MDA-MB 231, and PC3) with HaCat as a control cell line. Some species determined as critically endangered with minimal availability were propagated using in vitro plant tissue culture techniques. Molecular docking studies were carried out to illustrate binding orientations of the 30 Amaryllidaceae alkaloids identified in the active site of some molecular targets involved with anti-cancer activity for potential anti-cancer drugs. In gastric cancer cell line AGS, the best results (lower cell viability percentages) were obtained for Crinum jagus (48.06 ± 3.35%) and Eucharis bonplandii (45.79 ± 3.05%) at 30 µg/mL. The research focused on evaluating the identified alkaloids on the Bcl-2 protein family (Mcl-1 and Bcl-xL) and HK2, where the in vitro, in silico and statistical results suggest that powelline and buphanidrine alkaloids could present cytotoxic activity. Finally, combining experimental and theoretical assays allowed us to identify and characterize potentially useful alkaloids for cancer treatmentapplication/pdfTrujillo, L.; Bedoya, J.; Cortés, N.; Osorio, E.H.; Gallego, J.-C.; Leiva, H.; Castro, D.; Osorio, E. Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches. Molecules 2023, 28, 2601. https://doi.org/10.3390/ molecules2806260114203049https://hdl.handle.net/20.500.12313/3839engSuiza182601128MoleculesFerlay, J.; Colombet, M.; Soerjomataram, I.; Parkin, D.M.; Pineros, M.; Znaor, A.; Bray, F. Cancer statistics for the year 2020: An overview. Int. J. Cancer 2021, 149, 778–789Arnold, M.; Morgan, E.; Rumgay, H.; Mafra, A.; Singh, D.; Laversanne, M.; Vignat, J.; Gralow, J.R.; Cardoso, F.; Siesling, S.; et al. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 2022, 66, 15–23Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021, 71, 209–249Heer, E.; Harper, A.; Escandor, N.; Sung, H.; McCormack, V.; Fidler-Benaoudia, M.M. Global burden and trends in premenopausal and postmenopausal breast cancer: A population-based study. Lancet Glob. Health 2020, 8, e1027–e1037Gallagher, B.D.T.; Coughlin, E.C.; Nair-Shalliker, V.; McCaffery, K.; Smith, D.P. Socioeconomic differences in prostate cancer treatment: A systematic review and meta-analysis. Cancer Epidemiol. 2022, 79, 102164López, M.J.; Carbajal, J.; Alfaro, A.L.; Saravia, L.G.; Zanabria, E.D.; Araujo, J.M.; Quispe, L.; Vizcarra, K.A.; Buleje, J.L.; Choo, C.E.; et al. Characteristics of gastric cancer around the World. Crit. Rev. Oncol. Hematol. 2022, 181, 103841Nyame, Y.A.; Cooperberg, M.R.; Cumberbatch, M.G.; Eggener, S.E.; Etzioni, R.; Gomez, S.L.; Haiman, C.; Huang, F.; Lee, C.T.; Litwin, M.S.; et al. Deconstructing, addressing, and eliminating racial and ethnic inequities in prostate cancer care. Eur. Urol. 2022, 82, 341–351Bray, F.; Laversanne, M.; Weiderpass, E.; Soerjomataram, I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 2021, 127, 3029–3030Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics. CA Cancer J. Clin. 2022, 72, 7–33Miller, K.D.; Nogueira, L.; Mariotto, A.B.; Rowland, J.H.; Yabroff, K.R.; Alfano, C.M.; Jemal, A.; Kramer, J.L.; Siegel, R.L. Cancer treatment and survivorship statistics, 2019. CA Cancer J. Clin. 2019, 69, 363–385Koskas, M.; Amant, F.; Mirza, M.R.; Creutzberg, C.L. Cancer of the corpus uteri: 2021 update. Int. J. Gynecol. Obstet. 2021, 155, 45–60Patel, A.; Iyer, P.; Matsuzaki, S.; Matsuo, K.; Sood, A.K.; Fleming, N.D. Emerging trends in neoadjuvant chemotherapy for ovarian cancer. Cancers 2021, 13, 626Rangarajan, K.; Pucher, P.H.; Armstrong, T.; Bateman, A.; Hamady, Z. Systemic neoadjuvant chemotherapy in modern pancreatic cancer treatment: A systematic review and meta-analysis. Ann. R. Coll. Surg. Engl. 2019, 101, 453–462Groenewold, M.D.; Olthof, C.G.; Bosch, D.J. Anaesthesia after neoadjuvant chemotherapy, immunotherapy or radiotherapy. BJA Educ. 2022, 22, 12–19Wang, Z.; Mo, H.; He, Z.; Chen, A.; Cheng, P. Extracellular vesicles as an emerging drug delivery system for cancer treatment: Current strategies and recent advances. Biomed. Pharmacother. 2022, 153, 113480Anand, U.; Dey, A.; Singh, A.K.; Sanyal, R.; Mishra, A.; Pandey, D.K.; De Falco, V.; Upadhyay, A.; Kandimalla, R.; Chaudhary, A.; et al. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2023; in pressNguyen, L.T.S.; Jacob, M.A.C.; Parajón, E.; Robinson, D.N. Cancer as a biophysical disease: Targeting the mechanical-adaptability program. Biophys. J. 2022, 121, 3573–3585Babar, Q.; Saeed, A.; Tabish, T.A.; Pricl, S.; Townley, H.; Thorat, N. Novel epigenetic therapeutic strategies and targets in cancer. Biochim. Biophys. Acta Mol. Basis Dis. 2022, 1868, 166552Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 2020, 83, 770–803Lu, J.J.; Wang, Y.T. Identification of anti-cancer compounds from natural products. Chin. J. Nat. Med. 2020, 18, 481–482Qiu, S.; Sun, H.; Zhang, A.H.; Xu, H.Y.; Yan, G.L.; Han, Y.; Wang, X.J. Natural alkaloids: Basic aspects, biological roles, and future perspectives. Chin. J. Nat. Med. 2014, 12, 401–406Howes, M.J.R. The evolution of anticancer drug discovery from plants. Lancet Oncol. 2018, 19, 293–294Roussi, F.; Gueritte, F.; Fahy, J. The Vinca alkaloids. In Anticancer Agents from Natural Products, 2nd ed.; Cragg, G.M., Kingston, D.G.I., Newman, D.J., Eds.; CRC/Taylor & Francis: Boca Raton, FL, USA, 2012; pp. 177–198Cragg, G.M.; Pezzuto, J.M. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med. Princ. Pract. 2016, 25, 41–59Nair, J.J.; Van Staden, J.; Bastida, J. Cytotoxic alkaloid constituents of the Amaryllidaceae. Stud. Nat. Prod. Chem. 2016, 49, 107–156Berkov, S.; Osorio, E.; Viladomat, F.; Bastida, J. Chemodiversity, chemotaxonomy and chemoecology of Amaryllidaceae alkaloids. In Alkaloids: Chemistry and Biology; Knölker, H.-J., Ed.; Elsevier Inc.: Amsterdam, The Netherlands, 2020; Volume 83, pp. 113–185Kornienko, A.; Evidente, A. Chemistry, biology, and medicinal potential of narciclasine and its congeners. Chem. Rev. 2008, 108, 1982–2014Nair, J.J.; Bastida, J.; van Staden, J. In vivo cytotoxicity studies of Amaryllidaceae alkaloids. Nat. Prod. Commun. 2016, 11, 121–132Botteon, C.E.A.; Silva, L.B.; Ccana-Ccapatinta, G.V.; Silva, T.S.; Ambrosio, S.R.; Veneziani, R.C.S.; Bastos, J.K.; Marcato, P.D. Biosynthesis and characterization of gold nanoparticles using Brazilian red propolis and evaluation of its antimicrobial and anticancer activities. Sci. Rep. 2021, 11, 1974Omoruyi, S.I.; Kangwa, T.S.; Ibrakaw, A.S.; Cupido, C.N.; Marnewick, J.L.; Ekpo, O.E.; Hussein, A.A. Cytotoxic activities of selected plants of the family Amaryllidaceae on brain tumour cell lines. S. Afr. J Bot. 2021, 136, 118–125Silverstone, P. Los Muertos Vivientes: La Historia Natural de Cuatro Lirios Amazónicos Del Suroccidente de Colombia; Editorial Universidad del Valle: Santiago de Cali, Colombia, 2011; p. 24Fennell, C.; Crouch, N.; van Staden, J. Micropropagation of the River Lily, Crinum variabile (Amaryllidaceae). S. Afr. J. Bot. 2001, 67, 74–77Guerrero-Valencia, F.A.; Rodríguez-de la O, J.L.; De, J.; Juárez-Hernández, M.; Ayala-Arreola, J.; Ramírez-González, G. Micropropagation of Amazon Lily (Eucharis Grandiflora Planch. & Linden) Through Direct Organogenesis. Polibotánica 2021, 51, 141–153Akinyele, S.T.; Elusiyan, C.A.; Omisore, N.O.; Adewunmi, C.O. Antimalarial activities and alkaloids from Crinum jagus (Thomps) DANDY. J. Ethnopharmacol. 2022, 296, 115359Cortes, N.; Posada-Duque, R.A.; Alvarez, R.; Alzate, F.; Berkov, S.; Cardona-Gómez, G.P.; Osorio, E. Neuroprotective activity and acetylcholinesterase inhibition of five Amaryllidaceae species: A comparative study. Life Sci. 2015, 122, 42–50Cortes, N.; Castañeda, C.; Osorio, E.H.; Cardona-Gomez, G.P.; Osorio, E. Amaryllidaceae alkaloids as agents with protective effects against oxidative neural cell injury. Life Sci. 2018, 203, 54–65Ka, S.; Masi, M.; Merindol, N.; Di Lecce, R.; Plourde, M.B.; Seck, M.; Górecki, M.; Pescitelli, G.; Desgagne-Penix, I.; Evidente, A. Gigantelline, gigantellinine and gigancrinine, cherylline- and crinine-type alkaloids isolated from Crinum jagus with anti-acetylcholinesterase activity. Phytochemistry 2020, 175, 112390Cortes, N.; Posada-Duque, R.; Cardona-Gómez, G.P.; Bastida, J.; Osorio, E. Chapter 13—Amaryllidaceae alkaloids and neuronal cell protection. In Pathology, Oxidative Stress and Dietary Antioxidants; Preedy, V.R., Ed.; Academic Press: London, UK, 2020; pp. 135–144Trujillo-Chacón, L.M.; Alarcón-Enos, J.E.; Céspedes-Acuña, C.L.; Bustamante, L.; Baeza, M.; López, M.G.; Fernández-Mendívil, C.; Cabezas, F.; Pastene-Navarrete, E.R. Neuroprotective activity of isoquinoline alkaloids from of Chilean Amaryllidaceae plants against oxidative stress-induced cytotoxicity on human neuroblastoma SH-SY5Y cells and mouse hippocampal slice culture. Food Chem. Toxicol. 2019, 132, 110665Cortes, N.; Sabogal-Guaqueta, A.M.; Cardona-Gomez, G.P.; Osorio, E. Neuroprotection and improvement of the histopathological and behavioral impairments in a murine Alzheimer’s model treated with Zephyranthes carinata alkaloids. Biomed. Pharmacother. 2019, 110, 482–492Rojas-Vera, J.; Buitrago-Díaz, A.A.; Possamai, L.M.; Timmers, L.F.S.M.; Tallini, L.R.; Bastida, J. Alkaloid profile and cholinesterase inhibition activity of five species of Amaryllidaceae family collected from Mérida state-Venezuela. S. Afr. J. Bot. 2021, 136, 126–136Sierra, K.; de Andrade, J.P.; Tallini, L.R.; Osorio, E.H.; Yañéz, O.; Osorio, M.I.; Oleas, N.H.; García-Beltrán, O.; Borges, W.; Bastida, J.; et al. In vitro and in silico analysis of galanthine from Zephyranthes carinata as an inhibitor of acetylcholinesterase. Biomed. Pharmacother. 2022, 150, 113016Zhong, L.; Li, Y.; Xiong, L. Small molecules in targeted cancer therapy: Advances, challenges, and future perspectives. Sig. Transduct. Target Ther. 2021, 6, 201Nair, J.J.; Bastida, J.; Viladomat, F.; van Staden, J. Cytotoxic agents of the crinane series of Amaryllidaceae alkaloids. Nat. Prod. Commun. 2012, 7, 1677–1688Nair, J.J.; van Staden, J. Cytotoxicity studies of lycorine alkaloids of the Amaryllidaceae. Nat. Prod. Commun. 2014, 9, 1193–1210D’Aguanno, S.; Del Bufalo, D. Inhibition of anti-apoptotic Bcl-2 proteins in preclinical and clinical studies: Current Overview in Cancer. Cells 2020, 9, 1287Li, R.; Mei, S.; Ding, Q.; Wang, Q.; Yu, L.; Zi, F. A pan-cancer analysis of the role of hexokinase II (HK2) in human tumors. Sci. Rep. 2022, 12, 18807Basu, A. The interplay between apoptosis and cellular senescence: Bcl-2 family proteins as targets for cancer therapy. Pharmacol. Ther. 2022, 230, 107943Gryko, M.; Pryczynicz, A.; Guzińska-Ustymowicz, K.; Kamocki, Z.; Zaręba, K.; Kemona, A.; Kędra, B. Immunohistochemical assessment of apoptosis-associated proteins: p53, Bcl-xL, Bax and Bak in gastric cancer cells in correlation with clinical and pathomorphological factors. Adv. Med. Sci. 2012, 57, 77–83Yuan, L.W.; Yamashita, H.; Seto, Y. Glucose metabolism in gastric cancer: The cutting-edge. World J. Gastroenterol. 2016, 22, 2046–2059Chen, L.; Guo, L.; Sun, Z.; Yang, G.; Guo, J.; Chen, K.; Xiao, R.; Yang, X.; Sheng, L. Monoamine oxidase a is a major mediator of mitochondrial homeostasis and glycolysis in gastric cancer progression. Cancer Manag. Res. 2020, 12, 8023–8035Nguyen, M.; Marcellus, R.C.; Roulston, A.; Watson, M.; Serfass, L.; Murthy Madiraju, S.R.; Goulet, D.; Viallet, J.; Bélec, L.; Billot, X.; et al. Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proc. Natl. Acad. Sci. USA 2007, 104, 19512–19517Rahmani, M.; Aust, M.M.; Attkisson, E.; Williams, D.C.; Ferreira-Gonzalez, A.; Grant, S. Inhibition of Bcl-2 antiapoptotic members by obatoclax potently enhances sorafenib-induced apoptosis in human myeloid leukemia cells through a Bim-dependent process. Blood 2012, 119, 6089–6098Sebola, T.E.; Uche-Okereafor, N.C.; Mekuto, L.; Makatini, M.M.; Green, E.; Mavumengwana, V. Antibacterial and anticancer activity and untargeted secondary metabolite profiling of crude bacterial endophyte extracts from Crinum macowanii Baker Leaves. Int. J. Microbiol. 2020, 2020, 8839490Nair, J.J.; van Staden, J. Cytotoxic tazettine alkaloids of the plant family Amaryllidaceae. S. Afr. J. Bot. 2021, 136, 147–156Rice, L.J.; Finnie, J.F.; Van Staden, J. In vitro bulblet production of Brunsvigia undulata from twin-scales. S. Afr. J. Bot. 2011, 77, 305–312Murashige, T.; Skoog, F. A revised medium for rapid growth and bio assays with tobacco tissue cultures. Physiol. Plant. 1962, 15, 473–497Dartier, J.; Lemaitre, E.; Chourpa, I.; Goupille, C.; Servais, S.; Chevalier, S.; Mahéo, K.; Dumas, J.-F. ATP-dependent activity and mitochondrial localization of drug efflux pumps in doxorubicin-resistant breast cancer cells. Biochim. Biophys. Acta 2017, 5, 1075–1084Lee, Y.J.; Park, K.S.; Lee, S.H. Curcumin targets both apoptosis and necroptosis in acidity-tolerant prostate carcinoma cells. BioMed Res. Int. 2021, 2021, 8859181Morris, 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, 2785–2791Porter, J.; Payne, A.; de Candole, B.; Ford, D.; Hutchinson, B.; Trevitt, G.; Turner, J.; Edwards, C.; Watkins, C.; Whitcombe, I.; et al. Crystal Structure of Chimaeric Bcl2-xL and Phenyl Tetrahydroisoquinoline Amide Complex. Protein Data Bank 2008, 2W3LCzabotar, P.E.; Lee, E.F.; Smith, B.J.; Deshayes, K.; Zobel, K.; Fairlie, W.D.; Colman, P.M. Crystal structure of Bcl-xL in complex with ABT-737. Protein Data Bank 2007, 2YXJDutta, S.; Fire, E.; Grant, R.A.; Sauer, R.T.; Keating, A.E. MCL-1 complex with MCL-1-specific selected peptide. Protein Data Bank 2017, 3KZ0Lin, H.; Zeng, J.; Xie, R.; Schulz, M.J.; Tedesco, R.; Qu, J.; Erhard, K.F.; Mack, J.F.; Raha, K.; Rendina, A.R.; et al. Discovery of a novel 2,6-disubstituted glucosamine series of potent and selective Hexokinase 2 Inhibitors. ACS Med. Chem. Lett. 2016, 7, 217–222Sathishkumar, N.; Sathiyamoorthy, S.; Ramya, M.; Yang, D.-U.; Lee, H.N.; Yang, D.-C. Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng. J. Enzyme Inhib. Med. Chem. 2012, 27, 685–692Swargiary, G.; Mani, S. Molecular docking and simulation studies of phytocompounds derived from Centella asiatica and Andrographis paniculata against hexokinase II as mitocan agents. Mitochondrion 2021, 61, 138–146Kazi, A.; Sun, J.; Doi, K.; Sung, S.S.; Takahashi, Y.; Yin, H.; Rodriguez, J.M.; Becerril, J.; Berndt, N.; Hamilton, A.D.; et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J. Biol. Chem. 2011, 286, 9382–9392Dalafave, D.S.; Prisco, G. Inhibition of antiapoptotic BCL-XL, BCL-2, and MCL-1 proteins by small molecule mimetics. Cancer Inform. 2010, 9, CIN.S5065-177Khan, A.; Mohammad, T.; Shamsi, A.; Hussain, A.; Alajmi, M.F.; Husain, S.A.; Iqbal, M.A.; Hassan, M.I. Identification of plant-based hexokinase 2 inhibitors: Combined molecular docking and dynamics simulation studies. J. Biomol. Struct. Dyn. 2022, 40, 10319–10331Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem. 1998, 19, 1639–1662This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacional (CC BY 4.0)https://creativecommons.org/licenses/by-nc-nd/4.0/https://www.mdpi.com/1420-3049/28/6/2601Amaryllidaceae alkaloidsCancerCytotoxic activityIn silico assaysCytotoxic activity of Amaryllidaceae plants against cancer cells : biotechnological, in vitro, and in silico approachesArtículo de revistahttp://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/articlehttp://purl.org/redcol/resource_type/ARTinfo:eu-repo/semantics/publishedVersionPublicationTEXTCytotoxic Activity of Amaryllidaceae Plants against Cancer Cells Biotechnological, In Vitro, and In Silico Approaches - molecules-28-02601.pdf.txtCytotoxic Activity of Amaryllidaceae Plants against Cancer Cells Biotechnological, In Vitro, and In Silico Approaches - molecules-28-02601.pdf.txtExtracted texttext/plain4540https://repositorio.unibague.edu.co/bitstreams/160a92db-b76a-4464-bd13-e2b135b48f08/download0ca4ac20a2361b3f2961c3e5ba016eeeMD53THUMBNAILCytotoxic Activity of Amaryllidaceae Plants against Cancer Cells Biotechnological, In Vitro, and In Silico Approaches - molecules-28-02601.pdf.jpgCytotoxic Activity of Amaryllidaceae Plants against Cancer Cells Biotechnological, In Vitro, and In Silico Approaches - molecules-28-02601.pdf.jpgGenerated Thumbnailimage/jpeg12280https://repositorio.unibague.edu.co/bitstreams/2ff33373-a50d-4635-8c82-dd5f7372d51a/download8eb025e584b2738ead2f7efff1f37852MD54ORIGINALCytotoxic Activity of Amaryllidaceae Plants against Cancer Cells Biotechnological, In Vitro, and In Silico Approaches - molecules-28-02601.pdfCytotoxic Activity of Amaryllidaceae Plants against Cancer Cells Biotechnological, In Vitro, and In Silico Approaches - molecules-28-02601.pdfapplication/pdf86599https://repositorio.unibague.edu.co/bitstreams/88b430cb-defe-42bf-8c45-c46cdb7a745f/downloadd3f123285b9b2ba52633cf6aec2439edMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-8134https://repositorio.unibague.edu.co/bitstreams/9562c557-dc6f-4638-9b1e-0aa8ae9d5bb1/download2fa3e590786b9c0f3ceba1b9656b7ac3MD5220.500.12313/3839oai:repositorio.unibague.edu.co:20.500.12313/38392023-10-18 03:00:46.96https://creativecommons.org/licenses/by-nc-nd/4.0/This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).https://repositorio.unibague.edu.coRepositorio Institucional Universidad de Ibaguébdigital@metabiblioteca.comQ3JlYXRpdmUgQ29tbW9ucyBBdHRyaWJ1dGlvbi1Ob25Db21tZXJjaWFsLU5vRGVyaXZhdGl2ZXMgNC4wIEludGVybmF0aW9uYWwgTGljZW5zZQ0KaHR0cHM6Ly9jcmVhdGl2ZWNvbW1vbnMub3JnL2xpY2Vuc2VzL2J5LW5jLW5kLzQuMC8=