{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T18:43:20Z","timestamp":1788893000402,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007056","name":"National Nanotechnology Center","doi-asserted-by":"publisher","award":["P1751389 and P1851699"],"award-info":[{"award-number":["P1751389 and P1851699"]}],"id":[{"id":"10.13039\/501100007056","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004396","name":"Thailand Research Fund","doi-asserted-by":"publisher","award":["DBG6180030"],"award-info":[{"award-number":["DBG6180030"]}],"id":[{"id":"10.13039\/501100004396","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center of Excellence for Innovation in Chemistry, Ministry of Higher Education, Science, Research, and Innovation","award":["RU.APD18\/59-02"],"award-info":[{"award-number":["RU.APD18\/59-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Crinum asiaticum is a perennial herb widely distributed in many warmer regions, including Thailand, and is well-known for its medicinal and ornamental values. Crinum alkaloids contain numerous compounds, such as crinamine. Even though its mechanism of action is still unknown, crinamine was previously shown to possess anticancer activity. In this study, we demonstrate that crinamine was more cytotoxic to cervical cancer cells than normal cells. It also inhibited anchorage-independent tumor spheroid growth more effectively than existing chemotherapeutic drugs carboplatin and 5-fluorouracil or the CDK9 inhibitor FIT-039. Additionally, unlike cisplatin, crinamine induced apoptosis without promoting DNA double-strand breaks. It suppressed cervical cancer cell migration by inhibiting the expression of positive regulators of epithelial-mesenchymal transition SNAI1 and VIM. Importantly, crinamine also exerted anti-angiogenic activities by inhibiting secretion of VEGF-A protein in cervical cancer cells and blood vessel development in zebrafish embryos. Gene expression analysis revealed that its mechanism of action might be attributed, in part, to downregulation of cancer-related genes, such as AKT1, BCL2L1, CCND1, CDK4, PLK1, and RHOA. Our findings provide a first insight into crinamine\u2019s anticancer activity, highlighting its potential use as an alternative bioactive compound for cervical cancer chemoprevention and therapy.<\/jats:p>","DOI":"10.3390\/biom9090494","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T04:23:36Z","timestamp":1568694216000},"page":"494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Crinamine Induces Apoptosis and Inhibits Proliferation, Migration, and Angiogenesis in Cervical Cancer SiHa Cells"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4949-9477","authenticated-orcid":false,"given":"Phattharachanok","family":"Khumkhrong","sequence":"first","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitiya","family":"Piboonprai","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Waraluck","family":"Chaichompoo","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0138-2146","authenticated-orcid":false,"given":"Wittaya","family":"Pimtong","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4424-8898","authenticated-orcid":false,"given":"Mattaka","family":"Khongkow","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katawut","family":"Namdee","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angkana","family":"Jantimaporn","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanpen","family":"Japrung","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udom","family":"Asawapirom","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8919-3555","authenticated-orcid":false,"given":"Apichart","family":"Suksamrarn","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9128-4894","authenticated-orcid":false,"given":"Tawin","family":"Iempridee","sequence":"additional","affiliation":[{"name":"National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1002\/cncr.30667","article-title":"Cervical cancer: A global health crisis","volume":"123","author":"Small","year":"2017","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"369","DOI":"10.31557\/APJCP.2019.20.2.369","article-title":"Cervical cancer in Khon Kaen, Thailand: Analysis of 1990-2014 incidence data and prediction of future trends","volume":"20","author":"Saenrueang","year":"2019","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Virani, S., Bilheem, S., Chansaard, W., Chitapanarux, I., Daoprasert, K., Khuanchana, S., Leklob, A., Pongnikorn, D., Rozek, L., and Siriarechakul, S. (2017). National and subnational population-based incidence of cancer in Thailand: Assessing cancers with the highest burdens. Cancers, 9.","DOI":"10.3390\/cancers9080108"},{"key":"ref_4","unstructured":"Howlader, N., Noone, A.M., Krapcho, M., Miller, D., Brest, A., Yu, M., Ruhl, J., Tatalovich, Z., Mariotto, A., and Lewis, D.R. (2019). SEER Cancer Statistics Review, 1975-2016."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4649","DOI":"10.1200\/JCO.2009.21.8909","article-title":"Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: A Gynecologic Oncology Group study","volume":"27","author":"Monk","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fridlender, M., Kapulnik, Y., and Koltai, H. (2015). Plant derived substances with anti-cancer activity: From folklore to practice. Front. Plant. Sci.","DOI":"10.3389\/fpls.2015.00799"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.soncn.2019.02.003","article-title":"Cervical cancer: An overview of pathophysiology and management","volume":"35","author":"Johnson","year":"2019","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1007\/s12094-007-0138-9","article-title":"Natural products as leads to anticancer drugs","volume":"9","author":"Gordaliza","year":"2007","journal-title":"Clin. Transl. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1039\/c3np70005d","article-title":"Amaryllidaceae and Sceletium alkaloids","volume":"30","author":"Jin","year":"2013","journal-title":"Nat. Prod. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16562","DOI":"10.1039\/C4RA14666B","article-title":"Biological and pharmacological activities of Amaryllidaceae alkaloids","volume":"5","author":"He","year":"2015","journal-title":"RSC Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.chroma.2018.07.009","article-title":"Green techniques in comparison to conventional ones in the extraction of Amaryllidaceae alkaloids: Best solvents selection and parameters optimization","volume":"1567","author":"Takla","year":"2018","journal-title":"J. Chromatogr. A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.fct.2013.08.042","article-title":"Pharmacological and toxicological insights to the South African Amaryllidaceae","volume":"62","author":"Nair","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3329\/bjm.v28i1.11801","article-title":"Antibacterial, antioxidant and cytotoxic properties of Crinum asiaticum bulb extract","volume":"28","author":"Rahman","year":"2012","journal-title":"Bangla. J. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1007\/s11418-019-01304-9","article-title":"Two new alkaloids from Crinum asiaticum var","volume":"73","author":"Endo","year":"2019","journal-title":"japonicum. J. Nat. Med."},{"key":"ref_15","unstructured":"Smitinand, T. (2014). Thai Plant Names, rev. ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1002\/cbdv.200800273","article-title":"Chemical constituents of Crinum asiaticum L. var. sinicum Baker and their cytotoxic activities","volume":"6","author":"Sun","year":"2009","journal-title":"Chem. Biodivers."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1021\/np50098a017","article-title":"Cytotoxic and antimalarial alkaloids from the bulbs of Crinum amabile","volume":"56","author":"Likhitwitayawuid","year":"1993","journal-title":"J. Nat. Prod."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.phytochem.2007.01.006","article-title":"Selective apoptosis-inducing activity of crinum-type Amaryllidaceae alkaloids","volume":"68","author":"McNulty","year":"2007","journal-title":"Phytochemistry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1021\/np030529k","article-title":"New crinine-type alkaloids with inhibitory effect on induction of inducible nitric oxide synthase from Crinum yemense","volume":"67","author":"Morikawa","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1248\/bpb.29.2140","article-title":"Crinamine from Crinum asiaticum var. japonicum inhibits hypoxia inducible factor-1 activity but not activity of hypoxia inducible factor-2","volume":"29","author":"Kim","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.bbrc.2018.04.175","article-title":"Anticancer activity of arborinine from Glycosmis parva leaf extract in human cervical cancer cells","volume":"500","author":"Piboonprai","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., and Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol.","DOI":"10.1186\/gb-2002-3-7-research0034"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1111\/aji.12512","article-title":"Simple Plex(TM): A novel multi-analyte, automated microfluidic immunoassay platform for the detection of human and mouse cytokines and chemokines","volume":"75","author":"Aldo","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1177\/1535370215600102","article-title":"In vitro and in vivo characterization of the anticancer activity of Thai stingless bee (Tetragonula laeviceps) cerumen","volume":"241","author":"Nugitrangson","year":"2016","journal-title":"Exp. Biol. Med."},{"key":"ref_25","first-page":"2993","article-title":"Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells","volume":"29","author":"Badisa","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1126\/science.2451290","article-title":"Cell and environment interactions in tumor microregions: The multicell spheroid model","volume":"240","author":"Sutherland","year":"1988","journal-title":"Science"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S1040-8428(00)00086-X","article-title":"Multicellular resistance: A paradigm for clinical resistance?","volume":"36","author":"Desoize","year":"2000","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dufau, I., Frongia, C., Sicard, F., Dedieu, L., Cordelier, P., Ausseil, F., Ducommun, B., and Valette, A. (2012). Multicellular tumor spheroid model to evaluate spatio-temporal dynamics effect of chemotherapeutics: Application to the gemcitabine\/CHK1 inhibitor combination in pancreatic cancer. BMC Cancer.","DOI":"10.1186\/1471-2407-12-15"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1002\/cmdc.201700447","article-title":"Identification of Atuveciclib (BAY 1143572), the first highly selective, clinical PTEFb\/CDK9 inhibitor for the treatment of cancer","volume":"12","author":"Scholz","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.1158\/1078-0432.CCR-17-3119","article-title":"CDK9 inhibitor FIT-039 suppresses viral oncogenes E6 and E7 and has a therapeutic effect on HPV-induced neoplasia","volume":"24","author":"Ajiro","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1200\/JCO.1996.14.7.2120","article-title":"p53 and bcl-2 proteins as prognostic markers in human papillomavirus-associated cervical lesions","volume":"14","author":"Kurvinen","year":"1996","journal-title":"J. Clin. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1006\/gyno.1999.5715","article-title":"The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions","volume":"77","author":"Dimitrakakis","year":"2000","journal-title":"Gynecol. Oncol."},{"key":"ref_33","first-page":"12361","article-title":"Expressions and clinical significance of Bcl-2, Bcl-xL and c-IAP1 protein in cervical cancer","volume":"11","author":"Tuohetimulati","year":"2018","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/cas.12366","article-title":"Targeting DNA damage response in cancer therapy","volume":"105","author":"Hosoya","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1007\/s40265-015-0481-z","article-title":"Pharmacologic management of advanced cervical cancer: Antiangiogenesis therapy and immunotherapeutic considerations","volume":"75","author":"Longoria","year":"2015","journal-title":"Drugs"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rocha, C.R.R., Silva, M.M., Quinet, A., Cabral-Neto, J.B., and Menck, C.F.M. (2018). DNA repair pathways and cisplatin resistance: An intimate relationship. Clinics.","DOI":"10.6061\/clinics\/2018\/e478s"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bcp.2016.06.019","article-title":"Platinum-containing compound platinum pyrithione is stronger and safer than cisplatin in cancer therapy","volume":"116","author":"Zhao","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1158\/1535-7163.MCT-10-0735","article-title":"Pancratistatin selectively targets cancer cell mitochondria and reduces growth of human colon tumor xenografts","volume":"10","author":"Griffin","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.ejca.2012.12.027","article-title":"Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012","volume":"49","author":"Ferlay","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Li, H., Wu, X., and Cheng, X. (2016). Advances in diagnosis and treatment of metastatic cervical cancer. J. Gynecol. Oncol.","DOI":"10.3802\/jgo.2016.27.e43"},{"key":"ref_41","unstructured":"Pouliot, N., Pearson, H.B., and Burrows, A. (2013). Investigating Metastasis Using In Vitro Platforms. Madame Curie Bioscience Database, Landes Bioscience."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.canlet.2014.09.021","article-title":"EMT in cervical cancer: Its role in tumour progression and response to therapy","volume":"356","author":"Qureshi","year":"2015","journal-title":"Cancer Letters"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s10555-008-9169-0","article-title":"EMT, the cytoskeleton, and cancer cell invasion","volume":"28","author":"Yilmaz","year":"2009","journal-title":"Cancer Metastasis Rev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Vu, T., and Datta, P. (2017). Regulation of EMT in colorectal cancer: A culprit in metastasis. Cancers.","DOI":"10.3390\/cancers9120171"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"963","DOI":"10.2174\/15680096113136660102","article-title":"The role of Snail in EMT and tumorigenesis","volume":"13","author":"Wang","year":"2013","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nrc2131","article-title":"Snail, Zeb and bHLH factors in tumour progression: An alliance against the epithelial phenotype?","volume":"7","author":"Peinado","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1165\/rcmb.2013-0314TR","article-title":"The role of vimentin intermediate filaments in the progression of lung cancer","volume":"50","author":"Kidd","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Wu, S., Du, Y., Beckford, J., and Alachkar, H. (2018). Upregulation of the EMT marker vimentin is associated with poor clinical outcome in acute myeloid leukemia. J. Transl. Med.","DOI":"10.1186\/s12967-018-1539-y"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10911-010-9177-x","article-title":"Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer","volume":"15","author":"Radisky","year":"2010","journal-title":"J. Mammary Gland Biol. Neoplasia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/1758834014543794","article-title":"Targeting angiogenesis in advanced cervical cancer","volume":"6","author":"Eskander","year":"2014","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/joim.12019","article-title":"VEGFA and tumour angiogenesis","volume":"273","author":"Welsh","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"863","DOI":"10.21873\/invivo.11551","article-title":"Bevacizumab efficacy and recurrence pattern of persistent and metastatic cervical cancer","volume":"33","author":"Lee","year":"2019","journal-title":"In Vivo"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/S0140-6736(17)31607-0","article-title":"Bevacizumab for advanced cervical cancer: Final overall survival and adverse event analysis of a randomised, controlled, open-label, phase 3 trial (Gynecologic Oncology Group 240)","volume":"390","author":"Tewari","year":"2017","journal-title":"The Lancet"},{"key":"ref_54","first-page":"4529","article-title":"Research progress on the PI3K\/AKT signaling pathway in gynecological cancer","volume":"19","author":"Shi","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1002\/ijc.21461","article-title":"Molecular analysis of the PI3K-AKT pathway in uterine cervical neoplasia: Frequent PIK3CA amplification and AKT phosphorylation","volume":"118","author":"Bertelsen","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0304-3835(01)00457-8","article-title":"Alteration of cyclin D1 and CDK4 gene in carcinoma of uterine cervix","volume":"166","author":"Cheung","year":"2001","journal-title":"Cancer Lett."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Li, T., Assani, G., Ling, H., Zhou, Q., Zeng, Y., Zhou, F., and Zhou, Y. (2019). Ribociclib, a selective cyclin D kinase 4\/6 inhibitor, inhibits proliferation and induces apoptosis of human cervical cancer in vitro and in vivo. Biomed. Pharmacother.","DOI":"10.1016\/j.biopha.2019.108602"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1158\/0008-5472.CAN-16-1378","article-title":"Cervical cancer growth is regulated by a c-ABL\u2013PLK1 signaling axis","volume":"77","author":"Yang","year":"2017","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1080\/09168451.2014.943650","article-title":"Overexpression of RhoA promotes the proliferation and migration of cervical cancer cells","volume":"78","author":"Liu","year":"2014","journal-title":"Biosci. Biotechnol. Biochem."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/9\/494\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:20:46Z","timestamp":1760188846000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/9\/9\/494"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,16]]},"references-count":59,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["biom9090494"],"URL":"https:\/\/doi.org\/10.3390\/biom9090494","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,16]]}}}