{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:53:22Z","timestamp":1775832802099,"version":"3.50.1"},"reference-count":67,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MINCIENCIAS","award":["CT 812\u20132018"],"award-info":[{"award-number":["CT 812\u20132018"]}]},{"name":"MINCIENCIAS","award":["CI 1880"],"award-info":[{"award-number":["CI 1880"]}]},{"DOI":"10.13039\/501100007329","name":"Universidad del Valle","doi-asserted-by":"publisher","award":["CT 812\u20132018"],"award-info":[{"award-number":["CT 812\u20132018"]}],"id":[{"id":"10.13039\/501100007329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007329","name":"Universidad del Valle","doi-asserted-by":"publisher","award":["CI 1880"],"award-info":[{"award-number":["CI 1880"]}],"id":[{"id":"10.13039\/501100007329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Due to the lack of chemotherapeutic drugs that selectively affect cervical cancer cells, natural sources such as snake venom are currently being investigated for molecules with antitumor potential. Pllans\u2013II, a phospholipase A2 type\u2013Asp49 from Porthidium lansbergii lansbergii snake venom, induced cell death in a cervical cancer cell line\u2014Ca Ski\u2014related to dysfunction in the ability to resolve endoplasmic reticulum stress, evidenced by sub\u2013expression of genes such as PERK, ERO1 PDIs, HSP70, and CHOP. Western blot analysis validated the last two genes\u2032 sub\u2013expression at the protein level. In addition, Pllans\u2013II presented a dose\u2013dependent cytotoxic effect on cancer cells and an insignificant effect on healthy endothelial cells (HUVEC). Additionally, Pllans\u2013II inhibited cancer cells\u2032 adhesion and migration capacity, induced cell cycle arrest in the G2\/M phase, and induced apoptosis stimulated possibly by the extrinsic route. These results demonstrate for the first time that Pllans\u2013II has an antitumor effect on a squamous epithelial cervical cancer cell line and represents a possible biotechnological tool for designing a prominent antitumor agent.<\/jats:p>","DOI":"10.3390\/molecules27196491","type":"journal-article","created":{"date-parts":[[2022,10,9]],"date-time":"2022-10-09T23:31:43Z","timestamp":1665358303000},"page":"6491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pllans\u2013II Induces Cell Death in Cervical Cancer Squamous Epithelial Cells via Unfolded Protein Accumulation and Endoplasmic Reticulum Stress"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0494-4207","authenticated-orcid":false,"given":"Alejandro","family":"Montoya-G\u00f3mez","sequence":"first","affiliation":[{"name":"Grupo de Nutrici\u00f3n, Facultad de Salud, Universidad del Valle, Cali 760043, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-5452","authenticated-orcid":false,"given":"Nelson","family":"Rivera Franco","sequence":"additional","affiliation":[{"name":"TAO-Lab, Centre for Bioinformatics and Photonics-CIBioFi, Department of Biology, Universidad del Valle, Cali 760032, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7057-717X","authenticated-orcid":false,"given":"Leonel Ives","family":"Montealegre-Sanchez","sequence":"additional","affiliation":[{"name":"Grupo de Nutrici\u00f3n, Facultad de Salud, Universidad del Valle, Cali 760043, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Manuel","family":"Solano-Redondo","sequence":"additional","affiliation":[{"name":"Grupo Laboratorio de Herpetolog\u00eda, Facultad de Ciencias, Universidad del Valle, Cali 760043, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-6721","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Castillo","sequence":"additional","affiliation":[{"name":"TAO-Lab, Centre for Bioinformatics and Photonics-CIBioFi, Department of Biology, Universidad del Valle, Cali 760032, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0783-5839","authenticated-orcid":false,"given":"Mildrey","family":"Mosquera-Escudero","sequence":"additional","affiliation":[{"name":"Grupo de Nutrici\u00f3n, Facultad de Salud, Universidad del Valle, Cali 760043, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6043-1521","authenticated-orcid":false,"given":"Eli\u00e9cer","family":"Jim\u00e9nez-Charris","sequence":"additional","affiliation":[{"name":"Grupo de Nutrici\u00f3n, Facultad de Salud, Universidad del Valle, Cali 760043, Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11262-009-0412-8","article-title":"The biological properties of E6 and E7 oncoproteins from human papillomaviruses","volume":"40","author":"Ghittoni","year":"2010","journal-title":"Virus Genes"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ygyno.2014.01.042","article-title":"A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer","volume":"133","author":"Lorusso","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.ejphar.2014.07.025","article-title":"Cisplatin in cancer therapy: Molecular mechanisms of action","volume":"740","author":"Dasari","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"43373","DOI":"10.1038\/srep43373","article-title":"Combining metformin and nelfinavir exhibits synergistic effects against the growth of human cervical cancer cells and xenograft in nude mice","volume":"7","author":"Chenglai","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.clinthera.2016.02.007","article-title":"Beyond chemotherapy: An overview and review of targeted therapy in cervical cancer","volume":"38","author":"Crafton","year":"2016","journal-title":"Clin. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1574971","DOI":"10.1155\/2016\/1574971","article-title":"Bothrops jararaca and Bothrops erythromelas snake venoms promote cell cycle arrest and induce apoptosis via the mitochondrial depolarization of cervical cancer cells","volume":"2016","author":"Gomes","year":"2016","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/CCO.0b013e328363e11a","article-title":"Management of the late effects of treatments for gynecological cancer","volume":"25","author":"Andrews","year":"2013","journal-title":"Curr. Opin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"203639","DOI":"10.1155\/2014\/203639","article-title":"Antitumoral activity of snake venom proteins: New trends in cancer therapy","volume":"2014","author":"Calderon","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_10","unstructured":"Hernandez-Ledesma, B., and Hsieh, C. (2013). Snake venom peptides: Promising molecules with anti-tumor effects. Bioactive Food Peptides in Health and Disease, IntechOpen. Available online: https:\/\/www.intechopen.com\/chapters\/42419."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Moga, M.A., Dimienescu, O.G., Arv\u0103tescu, C.A., Ifteni, P., and Ple\u015f, L. (2018). Anticancer activity of toxins from bee and snake venom\u2014An overview on ovarian cancer. Molecules, 23.","DOI":"10.3390\/molecules23030692"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1007\/s11033-020-05503-6","article-title":"Cervical cancer and potential pharmacological treatment with snake venoms","volume":"47","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1042\/BST20200110","article-title":"Cytotoxicity of snake venom enzymatic toxins: Phospholipase A2 and l-amino acid oxidase","volume":"48","author":"Hiu","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1042\/BJ20080078","article-title":"Catalytically inactive phospholipase A2 homologue binds to vascular endothelial growth factor receptor-2 via a C-terminal loop region","volume":"411","author":"Fujisawa","year":"2008","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.biologicals.2009.01.010","article-title":"Antitumor effects of snake venom chemically modified Lys49 phospholipase A2-like BthTX-I and a synthetic peptide derived from its C-terminal region","volume":"37","author":"Gebrim","year":"2009","journal-title":"Biologicals"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.2174\/138161210793292456","article-title":"Synthetic peptides derived from the C-terminal region of Lys49 phospholipase A2 homologues from viperidae snake venoms: Biomimetic activities and potential applications","volume":"16","author":"Lomonte","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1016\/j.peptides.2008.05.021","article-title":"Myotoxic phospholipases A2 isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: Cytotoxic effect on microorganism and tumor cells","volume":"29","author":"Costa","year":"2008","journal-title":"Peptides"},{"key":"ref_18","first-page":"1","article-title":"Cytotoxic and pro-apoptotic action of MjTX-I, a phospholipase A2 isolated from Bothrops moojeni snake venom, towards leukemic cells","volume":"24","author":"Benati","year":"2019","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s40409-015-0044-5","article-title":"Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: Evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines","volume":"21","author":"Silva","year":"2015","journal-title":"J. Venom. Anim. Toxins Incl. Trop. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.ijbiomac.2015.10.080","article-title":"Human breast cancer cell death induced by BnSP-6, a Lys-49 PLA2 homologue from Bothrops pauloensis venom","volume":"82","author":"Azevedo","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ijbiomac.2018.06.082","article-title":"Genotoxic effects of BnSP-6, a Lys-49 phospholipase A2 (PLA2) homologue from Bothrops pauloensis snake venom, on MDA-MB-231 breast cancer cells","volume":"118","author":"Silva","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.matbio.2009.03.007","article-title":"MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration","volume":"28","author":"Bazaa","year":"2009","journal-title":"Matrix Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.ijbiomac.2019.05.164","article-title":"Antitumor and antimetastatic effects of PLA2-BthTX-II from Bothrops jararacussu venom on human breast cancer cells","volume":"135","author":"Lopes","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_24","first-page":"129","article-title":"Antiproliferative effects of snake venom phospholipases A2 and their perspectives for cancer treatment","volume":"Volume 1","author":"Gopalakrishnakone","year":"2017","journal-title":"Toxins and Drug Discovery, Toxinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jprot.2014.11.016","article-title":"Proteomic and functional analyses of the venom of Porthidium lansbergii lansbergii (Lansberg\u2019s hognose viper) from the Atlantic Department of Colombia","volume":"114","author":"Camacho","year":"2015","journal-title":"J. Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.toxicon.2016.07.006","article-title":"Divergent functional profiles of acidic and basic phospholipases A2 in the venom of the snake Porthidium lansbergii lansbergii","volume":"119","author":"Camacho","year":"2016","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.ijbiomac.2018.09.053","article-title":"Antitumor potential of Pllans-II, an acidic Asp49-PLA2 from Porthidium lansbergii lansbergii snake venom on human cervical carcinoma HeLa cells","volume":"122","author":"Lopes","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1099\/0022-1317-75-5-1139","article-title":"Differentiation-independent constitutive expression of the human papillomavirus type 16 E6 and E7 oncogenes in the CaSki cervical tumour cell line","volume":"75","author":"Choo","year":"1994","journal-title":"J. Gen. Vitol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.cellbi.2006.11.007","article-title":"Antitumor effects of cationic synthetic peptides derived from Lys49 phospholipase A2 homologues of snake venoms","volume":"31","author":"Araya","year":"2007","journal-title":"Cell Biol. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1111\/j.1745-7254.2007.00530.x","article-title":"Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells","volume":"28","author":"Yan","year":"2008","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_31","first-page":"42","article-title":"Purification of a phospholipase A2 from Daboia russelii siamensis venom with anticancer effects","volume":"2","author":"Khunsap","year":"2011","journal-title":"J. Venom Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e8055","DOI":"10.7717\/peerj.8055","article-title":"Phospholipase A2 from krait Bungarus fasciatus venom induces human cancer cell death in vitro","volume":"7","author":"Tran","year":"2019","journal-title":"PeerJ"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"894","DOI":"10.2174\/092986609788923266","article-title":"Snake venom phospholipases A2: A new class of antitumor agents","volume":"16","author":"Rodrigues","year":"2009","journal-title":"Protein Pept. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/35011084","article-title":"A receptor for phosphatidylserine-specific clearance of apoptotic cells","volume":"405","author":"Fadok","year":"2000","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1021\/jf205053r","article-title":"The chalcone flavokawain B induces G2\/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt\/p38 MAPK signaling pathway","volume":"60","author":"Hseu","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/35077213","article-title":"Proliferation, cell cycle and apoptosis in cancer","volume":"411","author":"Evan","year":"2001","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejphar.2012.10.013","article-title":"Anti-tumor effect of germacrone on human hepatoma cell lines through inducing G2\/M cell cycle arrest and promoting apoptosis","volume":"698","author":"Liu","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_39","first-page":"503","article-title":"Cytotoxic activity of NN-32 toxin from Indian spectacled cobra venom on human breast cancer cell line","volume":"17","author":"Attarde","year":"2017","journal-title":"Clin. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nrm3270","article-title":"The unfolded protein response: Controlling cell fate decisions under ER stress and beyond","volume":"13","author":"Hetz","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"109688","DOI":"10.1016\/j.biopha.2019.109688","article-title":"PDIA4: The basic characteristics, functions and its potential connection with cancer","volume":"122","author":"Wang","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1002\/hep.30917","article-title":"Mesencephalic Astrocyte-Derived Neurotrophic Factor Inhibits Liver Cancer Through Small Ubiquitin-Related Modifier (SUMO)ylation-Related Suppression of NF-\u03baB\/Snail Signaling Pathway and Epithelial-Mesenchymal Transition","volume":"71","author":"Liu","year":"2020","journal-title":"Hepatology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s12276-021-00560-8","article-title":"The aftermath of the interplay between the endoplasmic reticulum stress response and redox signaling","volume":"53","author":"Bhattarai","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.tibs.2018.06.005","article-title":"Quality control in the endoplasmic reticulum: Crosstalk between ERAD and UPR pathways","volume":"43","author":"Hwang","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1083\/jcb.201303027","article-title":"Ero1-\u03b1 and PDIs constitute a hierarchical electron transfer network of endoplasmic reticulum oxidoreductases","volume":"202","author":"Araki","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1089\/ars.2009.2880","article-title":"Redox state of the endoplasmic reticulum is controlled by ERO 1l-Alpha and intraluminal calcium","volume":"13","author":"Enyedi","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6161","DOI":"10.1073\/pnas.92.13.6161","article-title":"The alpha 5 beta 1 integrin supports survival of cells on fibronectin and up-regulates Bcl-2 expression","volume":"92","author":"Zhang","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1083\/jcb.141.4.1019","article-title":"The \u03b15\u03b21 integrin mediates elimination of amyloid-\u03b2 peptide and protects against apoptosis","volume":"141","author":"Matter","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1593\/tlo.08187","article-title":"\u03b15\u03b21 integrin ligand PHSRN induces invasion and \u03b15 mRNA in endothelial cells to stimulate angiogenesis","volume":"2","author":"Zeng","year":"2009","journal-title":"Transl. Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.7314\/APJCP.2013.14.6.3891","article-title":"Prognostic significance of \u03b15\u03b21-integrin expression in cervical cancer","volume":"14","author":"Wang","year":"2013","journal-title":"Asian Pacific J. Cancer Prev."},{"key":"ref_51","first-page":"283181","article-title":"Integrin signaling in cancer cell survival and chemoresistance","volume":"2012","author":"Aoudjit","year":"2012","journal-title":"Chemother. Res. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.1016\/j.bbamcr.2013.06.026","article-title":"Anoikis molecular pathways and its role in cancer progression","volume":"1833","author":"Paoli","year":"2013","journal-title":"Biochim. Biophys. Acta (BBA)-Mol. Cell Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3616","DOI":"10.1128\/MCB.05164-11","article-title":"PERK integrates autophagy and oxidative stress responses to promote survival during extracellular matrix detachment","volume":"31","author":"Salas","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1158\/2159-8290.CD-13-0945","article-title":"Epithelial-to-mesenchymal transition activates PERK-eIF2\u03b1 and sensitizes cells to endoplasmic reticulum stress","volume":"4","author":"Feng","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2592","DOI":"10.1172\/JCI78031","article-title":"ATF4-dependent induction of heme oxygenase 1 prevents anoikis and promotes metastasis","volume":"125","author":"Dey","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.3389\/fonc.2020.01100","article-title":"Endoplasmic reticulum stress in bone metastases","volume":"10","author":"Xu","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1080\/21541248.2017.1362495","article-title":"Regulation and functions of RhoU and RhoV","volume":"11","author":"Hodge","year":"2017","journal-title":"Small GTPases"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.2174\/1568026619666190806151401","article-title":"Antitumoral Potential of Lansbermin-I, a Novel Disintegrin from Porthidium lansbergii lansbergii Venom on Breast Cancer Cells","volume":"19","author":"Gimenes","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1177\/1087057110361772","article-title":"A simplified method for quantifying cell migration\/wound healing in 96-well plates","volume":"15","author":"Yue","year":"2010","journal-title":"J. Biomol. Screen"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1083\/jcb.66.1.188","article-title":"Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining","volume":"66","author":"Krishan","year":"1975","journal-title":"J. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0091-679X(10)96020-2","article-title":"Electron microscopy of the mouse central nervous system","volume":"96","author":"Cooper","year":"2010","journal-title":"Methods Cell Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"FeatureCounts: An efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_65","unstructured":"Blighe, K., Rana, S., and Lewis, M. (2022, May 11). EnhancedVolcano: Publication-Ready Volcano Plots with Enhanced Colouring and Labeling, R Packag. Version. 1.2.0. Available online: https:\/\/bioconductor.org\/packages\/devel\/bioc\/vignettes\/EnhancedVolcano\/inst\/doc\/EnhancedVolcano.html."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"ClusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS  J. Integr. Biol."},{"key":"ref_67","unstructured":"Yu, G. (2022, May 11). Enrichplot: Visualization of Functional Enrichment Result. R Packag. Version  1. Volume 1. Available online: https:\/\/www.bioconductor.org\/packages\/release\/bioc\/html\/enrichplot.html."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6491\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:14Z","timestamp":1760143514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/19\/6491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":67,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27196491"],"URL":"https:\/\/doi.org\/10.3390\/molecules27196491","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}