{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:44:01Z","timestamp":1787507041708,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31861143050"],"award-info":[{"award-number":["31861143050"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Academy of Scientific Research and Technology","award":["31861143050"],"award-info":[{"award-number":["31861143050"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Research has been conducted to investigate the potential application of scorpion venom-derived peptides in cancer therapy. Smp43, a cationic antimicrobial peptide from Scorpio maurus palmatus venom, has been found to exhibit suppressive activity against the proliferation of multiple cancer cell lines. However, its impact on non-small-cell lung cancer (NSCLC) cell lines has not been previously investigated. This study aimed to determine the cytotoxicity of Smp43 towards various NSCLC cell lines, particularly A549 cells with an IC50 value of 2.58 \u03bcM. The results indicated that Smp43 was internalized into A549 cells through membranolysis and endocytosis, which caused cytoskeleton disorganization, a loss of mitochondrial membrane potential, an accumulation of reactive oxygen species (ROS), and abnormal apoptosis, cell cycle distribution, and autophagy due to mitochondrial dysfunction. Additionally, the study explored the in vivo protective effect of Smp43 in xenograft mice. The findings suggest that Smp43 has potential anticarcinoma properties exerted via the inducement of cellular processes related to cell membrane disruption and mitochondrial dysfunction.<\/jats:p>","DOI":"10.3390\/toxins15050347","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T02:00:27Z","timestamp":1684720827000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Potent Antitumor Activity of Smp43 against Non-Small-Cell Lung Cancer A549 Cells via Inducing Membranolysis and Mitochondrial Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"given":"Ze","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahua","family":"Gao","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tienthanh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinwei","family":"Chai","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiena","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3862-5535","authenticated-orcid":false,"given":"Mohamed A.","family":"Abdel-Rahman","sequence":"additional","affiliation":[{"name":"Zoology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4525-5803","authenticated-orcid":false,"given":"Xueqing","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/S0025-6196(11)60735-0","article-title":"Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship","volume":"83","author":"Molina","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.3389\/fimmu.2020.02030","article-title":"Antimicrobial peptides as potential antiviral factors in insect antiviral immune response","volume":"11","author":"Feng","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Tornesello, A.L., Borrelli, A., Buonaguro, L., Buonaguro, F.M., and Tornesello, M.L. (2020). Antimicrobial peptides as anticancer agents: Functional properties and biological activities. Molecules, 25.","DOI":"10.3390\/molecules25122850"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.3389\/fimmu.2020.02077","article-title":"The dual role of antimicrobial peptides in autoimmunity","volume":"11","author":"Liang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"46635","DOI":"10.18632\/oncotarget.16743","article-title":"Antimicrobial peptides with selective antitumor mechanisms: Prospect for anticancer applications","volume":"8","author":"Deslouches","year":"2017","journal-title":"Oncotarget"},{"key":"ref_6","first-page":"3919","article-title":"The antimicrobial peptides and their potential clinical applications","volume":"11","author":"Lei","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Guo, R., Liu, J., Chai, J., Gao, Y., Abdel-Rahman, M.A., and Xu, X. (2022). Scorpion peptide Smp24 exhibits a potent antitumor effect on human lung cancer cells by damaging the membrane and cytoskeleton in vivo and in vitro. Toxins, 14.","DOI":"10.3390\/toxins14070438"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"23558","DOI":"10.1074\/jbc.M109.023358","article-title":"Drosomycin, an innate immunity peptide of Drosophila melanogaster, interacts with the fly voltage-gated sodium channel","volume":"284","author":"Cohen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1038\/nrd1197","article-title":"Therapeutic potential of venom peptides","volume":"2","author":"Lewis","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejphar.2010.10.066","article-title":"Anti-proliferative effect of Kv1.3 blockers in A549 human lung adenocarcinoma in vitro and in vivo","volume":"651","author":"Jang","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Nguyen, T., Guo, R., Chai, J., Wu, J., Liu, J., Chen, X., Abdel-Rahman, M.A., Xia, H., and Xu, X. (2022). Smp24, a scorpion-venom peptide, exhibits potent antitumor effects against hepatoma HepG2 cells via multi-mechanisms in vivo and in vitro. Toxins, 14.","DOI":"10.3390\/toxins14100717"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Guo, R., Chen, X., Nguyen, T., Chai, J., Gao, Y., Wu, J., Li, J., Abdel-Rahman, M.A., Chen, X., and Xu, X. (2022). The strong anti-tumor effect of Smp24 in lung adenocarcinoma A549 cells depends on its induction of mitochondrial dysfunctions and ROS accumulation. Toxins, 14.","DOI":"10.3390\/toxins14090590"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"788874","DOI":"10.3389\/fphar.2021.788874","article-title":"Scorpion venom antimicrobial peptides induce caspase-1 dependant pyroptotic cell death","volume":"12","author":"Elrayess","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1021\/acs.jnatprod.1c00963","article-title":"Antitumor effects of scorpion peptide Smp43 through mitochondrial dysfunction and membrane disruption on hepatocellular carcinoma","volume":"84","author":"Chai","year":"2021","journal-title":"J. Nat. Prod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1042\/BST0350788","article-title":"Cell-surface proteoglycans as molecular portals for cationic peptide and polymer entry into cells","volume":"35","author":"Poon","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev.biophys.37.032807.125912","article-title":"Mediation, modulation, and consequences of membrane-cytoskeleton interactions","volume":"37","author":"Doherty","year":"2008","journal-title":"Annu. Rev. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.trecan.2017.10.006","article-title":"Mitochondria, Bioenergetics and apoptosis in cancer","volume":"3","author":"Burke","year":"2017","journal-title":"Trends Cancer."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"292","DOI":"10.3389\/fonc.2013.00292","article-title":"Mitochondrial dysfunction in cancer","volume":"3","author":"Boland","year":"2013","journal-title":"Front. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1124\/mol.114.091850","article-title":"Autophagy and cancer therapy","volume":"85","author":"Thorburn","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0076-6879(08)03612-4","article-title":"Monitoring autophagic degradation of p62\/SQSTM1","volume":"452","author":"Lamark","year":"2009","journal-title":"Methods Enzymol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3389\/fmicb.2013.00294","article-title":"Castanho. From antimicrobial to anticancer peptides. A review","volume":"4","author":"Gaspar","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/10428199409049727","article-title":"Membrane fluidity and adherence to extracellular matrix components are related to blast cell count in acute myeloid leukemia","volume":"15","author":"Berger","year":"1994","journal-title":"Leuk. Lymphoma"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.188.4190.819","article-title":"Microvilli: A major difference between normal and cancer cells?","volume":"188","author":"Kolata","year":"1975","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.bbamem.2007.11.008","article-title":"Studies on anticancer activities of antimicrobial peptides","volume":"1778","author":"Hoskin","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8293","DOI":"10.1038\/s41598-017-08963-2","article-title":"Cell surface binding, uptaking and anticancer activity of L-K6, a lysine\/leucine-rich peptide, on human breast cancer MCF-7 cells","volume":"7","author":"Wang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10555-008-9166-3","article-title":"The cytoskeleton and cancer","volume":"28","author":"Hall","year":"2009","journal-title":"Cancer Metastasis Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/bph.12704","article-title":"Movers and shakers: Cell cytoskeleton in cancer metastasis","volume":"171","author":"Fife","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.1600-0854.2004.00196.x","article-title":"Actin and microtubules in cell motility: Which one is in control?","volume":"5","year":"2004","journal-title":"Traffic"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"795838","DOI":"10.3389\/fcell.2021.795838","article-title":"Regulation of mitochondrial function by the actin cytoskeleton","volume":"9","author":"Illescas","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nrm1682","article-title":"The actin cytoskeleton: A key regulator of apoptosis and ageing?","volume":"6","author":"Gourlay","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1006\/exnr.1999.7197","article-title":"Cyclosporin A attenuates acute mitochondrial dysfunction following traumatic brain injury","volume":"160","author":"Sullivan","year":"1999","journal-title":"Exp. Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R551","DOI":"10.1016\/j.cub.2006.06.054","article-title":"Mitochondria: More than just a powerhouse","volume":"16","author":"McBride","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.3390\/md9101995","article-title":"Pardaxin, an antimicrobial peptide, triggers caspase-dependent and ROS-mediated apoptosis in HT-1080 cells","volume":"9","author":"Huang","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/nrc2657","article-title":"p21 in cancer: Intricate networks and multiple activities","volume":"9","author":"Abbas","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Yun, C.W., and Lee, S.H. (2018). The roles of autophagy in cancer. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113466"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.3892\/ol.2017.6565","article-title":"Curcumin induced autophagy anticancer effects on human lung adenocarcinoma cell line A549","volume":"14","author":"Liu","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e63641","DOI":"10.1371\/journal.pone.0063641","article-title":"FK-16 derived from the anticancer peptide LL-37 induces caspase-independent apoptosis and autophagic cell death in colon cancer cells","volume":"8","author":"Ren","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_38","first-page":"214","article-title":"Bcl-2: Beclin 1 complex: Multiple, mechanisms regulating autophagy\/apoptosis toggle switch","volume":"2","author":"Marquez","year":"2012","journal-title":"Am. J. Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/cdd.2010.191","article-title":"The Beclin 1 network regulates autophagy and apoptosis","volume":"18","author":"Kang","year":"2011","journal-title":"Cell Death Differ."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8266","DOI":"10.1021\/jf901054c","article-title":"Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway","volume":"57","author":"Yo","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3961","DOI":"10.2147\/DDDT.S181939","article-title":"Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K\/AKT pathway in vivo and vitro","volume":"12","author":"Yan","year":"2018","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3559","DOI":"10.3892\/or.2016.5138","article-title":"Salidroside induces apoptosis and autophagy in human colorectal cancer cells through inhibition of PI3K\/Akt\/mTOR pathway","volume":"36","author":"Fan","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"108939","DOI":"10.1016\/j.cbi.2020.108939","article-title":"Cantharidin suppresses gastric cancer cell migration\/invasion by inhibiting the PI3K\/Akt signaling pathway via CCAT1","volume":"317","author":"Song","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3892\/ol.2016.4606","article-title":"Gefitinib induces lung cancer cell autophagy and apoptosis via blockade of the PI3K\/AKT\/mTOR pathway","volume":"12","author":"Zhao","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41392-022-00904-4","article-title":"Therapeutic peptides: Current applications and future directions","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Luo, X., Ding, L., Ye, X., Zhu, W., Zhang, K., Li, F., Jiang, H., Zhao, Z., and Chen, Z. (2021). An Smp43-Derived Short-Chain \u03b1-Helical Peptide Displays a Unique Sequence and Possesses Antimicrobial Activity against Both Gram-Positive and Gram-Negative Bacteria. Toxins, 13.","DOI":"10.3390\/toxins13050343"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.toxicon.2016.03.014","article-title":"Characterisation of three alpha-helical antimicrobial peptides from the venom of Scorpio maurus palmatus","volume":"117","author":"Harrison","year":"2016","journal-title":"Toxicon"}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/15\/5\/347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:38:54Z","timestamp":1760125134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/15\/5\/347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["toxins15050347"],"URL":"https:\/\/doi.org\/10.3390\/toxins15050347","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}