{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:04:33Z","timestamp":1788401073221,"version":"build-2803163510"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K17147, 23K09317, 24K12888"],"award-info":[{"award-number":["23K17147, 23K09317, 24K12888"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Recent studies have elucidated a potential correlation between oral carcinogenesis and the oral microbiome. However, few reports exist on the interaction between <jats:italic>Streptococcus<\/jats:italic> spp., the most common oral microflora bacterium, and oral cancer. In this study, we aimed to elucidate the effects of <jats:italic>Streptococcus<\/jats:italic> spp. on oral squamous cell carcinoma (OSCC) cells <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>HSC-3 (tongue carcinoma) and Ca9-22 (gingival carcinoma) cells were used as models of OSCC cells, and their responses were examined after adding major oral <jats:italic>Streptococcus<\/jats:italic> species\u2014<jats:italic>S. mitis<\/jats:italic>, <jats:italic>S. sanguinis<\/jats:italic>, <jats:italic>S. anginosus<\/jats:italic>, <jats:italic>S. salivarius<\/jats:italic>, and <jats:italic>S. mutans<\/jats:italic>\u2014to the culture medium. Cell viability was assessed using the CCK-8 assay. Gene expression changes were analyzed using RNA sequencing and RT-qPCR followed by Gene Ontology analysis. Flow cytometry was used to observe the effects of bacteria on the cell cycle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among all examined <jats:italic>Streptococcus<\/jats:italic> species, <jats:italic>S. mitis<\/jats:italic> had the strongest inhibitory effect on the growth of OSCC cells. RNA sequencing and RT-qPCR revealed an increase in the number of genes involved in mitotic nuclear division, especially <jats:italic>DUSP1<\/jats:italic>, in HSC-3 cells treated with <jats:italic>S. mitis.<\/jats:italic> Flow cytometry showed that <jats:italic>S. mitis<\/jats:italic> caused a decreased number of HSC-3 cells in the G0\/G1 phase and an increased number in the G2\/M phase, suggesting cell cycle arrest in the G2\/M phase. Various treatments of <jats:italic>S. mitis<\/jats:italic> were used to examine the effects of intact bacteria and bacterial components on cancer cells, indicating the involvement of structural bacterial proteins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study, investigating the association between oral cancer cells and bacteria of the genus <jats:italic>Streptococcus<\/jats:italic>, revealed that <jats:italic>S. mitis<\/jats:italic> may play an important role in the inhibition of cancer cells.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1524820","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T05:35:21Z","timestamp":1746768921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["In vitro impact of Streptococcus mitis on the inhibition of oral cancer cell proliferation via mitotic modulation"],"prefix":"10.3389","volume":"15","author":[{"given":"Inori","family":"Inui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichi","family":"Mochizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumika","family":"Hirabayashi-Nishimuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshie","family":"Yoshioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Sasaguri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Habu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Ariyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Yamasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3481","DOI":"10.1002\/jcp.25809","article-title":"Mechanisms involved in enhancement of matrix metalloproteinase-9 expression in macrophages by interleukin-33","volume":"232","author":"Ariyoshi","year":"2017","journal-title":"J. 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