{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:39:29Z","timestamp":1791581969731,"version":"4.3.4"},"reference-count":23,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>It remains unclear how metabolites produced by vaginal peroxide-producing lactobacilli influence parameters supporting cervical cancer cell survival. The aim of our study was to investigate the functional response of HeLa cells to cell-free metabolites of vaginal lactobacilli producing peroxide under conditions of oxidative stress. HeLa cells were treated with cell-free metabolites of lactobacilli isolated from the vaginal fluid of healthy women. Subsequently, their resistance to oxidative stress (total number of surviving, apoptotic, and necrotic cells), dehydrogenase activity with the MTT assay, and mitochondrial potential were measured. Pretreatment with cell-free lactobacilli metabolites significantly reduced HeLa cell survival under oxidative stress in most cases; dehydrogenase activity and mitochondrial potential changed to a lesser extent. All HeLa cells pretreated with cell-free lactobacillus metabolites that died due to oxidative stress died apoptotic death. These effects of cell-free lactobacilli metabolites are not always determined by lactic acid levels. These data reveal a new mechanism by which vaginal lactobacilli exert local antitumor protection by inducing controlled cell death in transformed cells.<\/jats:p>","DOI":"10.3390\/ijms262411929","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:39:18Z","timestamp":1765442358000},"page":"11929","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Effect of Cell-Free Metabolites of Vaginal Lactobacilli on HeLa Cells Is Independent of Lactic Acid Concentration"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3237-8211","authenticated-orcid":false,"given":"Yulia","family":"Myachina","sequence":"first","affiliation":[{"name":"Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, Pionerskaya St. 11, Orenburg 460000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1866-1678","authenticated-orcid":false,"given":"Andrey","family":"Sgibnev","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Intracellular Symbiosis of the Ural Branch of the Russian Academy of Sciences, Pionerskaya St. 11, Orenburg 460000, Russia"},{"name":"Department of Chemistry, Orenburg State Medical University, Sovietskaya St. 6, Orenburg 460000, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Petrova, M.I., Lievens, E., Malik, S., Imholz, N., and Lebeer, S. (2015). Lactobacillus Species as Biomarkers and Agents That Can Promote Various Aspects of Vaginal Health. Front. Physiol., 6.","DOI":"10.3389\/fphys.2015.00081"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00404-013-3064-9","article-title":"The Role of Lactobacilli and Probiotics in Maintaining Vaginal Health","volume":"289","author":"Borges","year":"2014","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"O\u2019Hanlon, D.E., Moench, T.R., and Cone, R.A. (2011). In Vaginal Fluid, Bacteria Associated with Bacterial Vaginosis Can Be Suppressed with Lactic Acid but Not Hydrogen Peroxide. BMC Infect. Dis., 11.","DOI":"10.1186\/1471-2334-11-200"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/s00253-016-7885-x","article-title":"Design and Validation of an Orally Administrated Active L. fermentum-L. acidophilus Probiotic Formulation Using Colorectal Cancer Apc Min\/+ Mouse Model","volume":"101","author":"Kahouli","year":"2017","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Lee, J.-E., Lee, J., Kim, J.H., Cho, N., Lee, S.H., Park, S.B., Koh, B., Kang, D., Kim, S., and Yoo, H.M. (2019). Characterization of the Anti-Cancer Activity of the Probiotic Bacterium Lactobacillus fermentum Using 2D vs. 3D Culture in Colorectal Cancer Cells. Biomolecules, 9.","DOI":"10.3390\/biom9100557"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"126839","DOI":"10.1016\/j.talanta.2024.126839","article-title":"Metabolomics and Proteomics Reveal the Inhibitory Effect of Lactobacillus crispatus on Cervical Cancer","volume":"281","author":"Zhong","year":"2025","journal-title":"Talanta"},{"key":"ref_7","first-page":"209","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_8","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/nrd2803","article-title":"Targeting Cancer Cells by ROS-Mediated Mechanisms: A Radical Therapeutic Approach?","volume":"8","author":"Trachootham","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s12276-020-0384-2","article-title":"ROS in Cancer Therapy: The Bright Side of the Moon","volume":"52","author":"Perillo","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chuah, L.-O., Foo, H.L., Loh, T.C., Mohammed Alitheen, N.B., Yeap, S.K., Abdul Mutalib, N.E., Abdul Rahim, R., and Yusoff, K. (2019). Postbiotic Metabolites Produced by Lactobacillus plantarum Strains Exert Selective Cytotoxicity Effects on Cancer Cells. BMC Complement. Altern. Med., 19.","DOI":"10.1186\/s12906-019-2528-2"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"\u015ali\u017cewska, K., Markowiak-Kope\u0107, P., and \u015ali\u017cewska, W. (2021). The Role of Probiotics in Cancer Prevention. Cancers, 13.","DOI":"10.3390\/cancers13010020"},{"key":"ref_12","first-page":"1465","article-title":"Surfacing Role of Probiotics in Cancer Prophylaxis and Therapy: A Systematic Review","volume":"36","author":"Dasari","year":"2017","journal-title":"Clin. Nutr. Edinb. Scotl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s12602-016-9238-6","article-title":"Influence of Hydrogen Peroxide, Lactic Acid, and Surfactants from Vaginal Lactobacilli on the Antibiotic Sensitivity of Opportunistic Bacteria","volume":"9","author":"Sgibnev","year":"2017","journal-title":"Probiotic Antimicrob. Proteins"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/ijc.30716","article-title":"Worldwide Burden of Cancer Attributable to HPV by Site, Country and HPV Type","volume":"141","author":"Plummer","year":"2017","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular Mechanisms of Cell Death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_16","first-page":"601","article-title":"The Effect of Lactobacillus crispatus and Lactobacillus rhamnosus Culture Supernatants on Expression of Autophagy Genes and HPV E6 and E7 Oncogenes in The HeLa Cell Line","volume":"17","author":"Motevaseli","year":"2016","journal-title":"Cell J. Yakhteh"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Heo, S., Kim, S., and Kang, D. (2020). The Role of Hydrogen Peroxide and Peroxiredoxins throughout the Cell Cycle. Antioxidants, 9.","DOI":"10.3390\/antiox9040280"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ali, T., Li, D., Ponnamperumage, T.N.F., Peterson, A.K., Pandey, J., Fatima, K., Brzezinski, J., Jakusz, J.A.R., Gao, H., and Koelsch, G.E. (2024). Generation of Hydrogen Peroxide in Cancer Cells: Advancing Therapeutic Approaches for Cancer Treatment. Cancers, 16.","DOI":"10.20944\/preprints202405.0194.v1"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fr\u0105szczak, K., Barczy\u0144ski, B., Siwiec, R., Kondracka, A., Malm, A., Kotarski, J., Witt, E., and Korona-G\u0142owniak, I. (2023). The Analysis of Lactobacillus Spp. Distribution in the Vaginal Microbiota of Polish Women with Abnormal Pap Smear Result. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1257587"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/s13205-023-03759-w","article-title":"Effect of Differential Deprivation of Nutrients on Cellular Proliferation, Oxidative Stress, Mitochondrial Function, and Cell Migration in MDA-MB-231, HepG2, and HeLa Cells","volume":"13","author":"Prasad","year":"2023","journal-title":"3 Biotech"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1.1.1\u20131.1.22","DOI":"10.1002\/0471143030.cb0101s66","article-title":"Basic Techniques in Mammalian Cell Tissue Culture","volume":"66","author":"Phelan","year":"2015","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/978-1-61779-080-5_20","article-title":"Cell Sensitivity Assays: The MTT Assay","volume":"731","author":"Kaspers","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102245","DOI":"10.1016\/j.redox.2022.102245","article-title":"Resistance to H2O2-Induced Oxidative Stress in Human Cells of Different Phenotypes","volume":"50","author":"Zenin","year":"2022","journal-title":"Redox Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11929\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:40:42Z","timestamp":1765442442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":23,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411929"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411929","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]}}}