{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T02:52:29Z","timestamp":1770519149998,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T00:00:00Z","timestamp":1618790400000},"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>Platyphyllenone is a type of diarylheptanoid that exhibits anti-inflammatory and chemoprotective effects. However, its effect on oral cancer remains unclear. In this study, we investigated whether platyphyllenone can promote apoptosis and autophagy in SCC-9 and SCC-47 cells. We found that it dose-dependently promoted the cleavage of PARP; caspase-3, -8, and -9 protein expression; and also led to cell cycle arrest at the G2\/M phase. Platyphyllenone up-regulated LC3-II and p62 protein expression in both SCC-9 and SCC-47 cell lines, implying that it can induce autophagy. Furthermore, the results demonstrated that platyphyllenone significantly decreased p-AKT and increased p-JNK1\/2 mitogen-activated protein kinase (MAPK) signaling pathway in a dose-dependent manner. The specific inhibitors of p-JNK1\/2 also reduced platyphyllenone-induced cleavage of PARP, caspase-3, and caspase -8, LC3-II and p62 protein expression. These findings are the first to demonstrate that platyphyllenone can induce both autophagy and apoptosis in oral cancers, and it is expected to provide a therapeutic option as a chemopreventive agent against oral cancer proliferation.<\/jats:p>","DOI":"10.3390\/ijms22084211","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:21:38Z","timestamp":1618831298000},"page":"4211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Platyphyllenone Induces Autophagy and Apoptosis by Modulating the AKT and JNK Mitogen-Activated Protein Kinase Pathways in Oral Cancer Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Yen-Tze","family":"Liu","sequence":"first","affiliation":[{"name":"Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Family Medicine, Changhua Christian Hospital, Changhua 500, Taiwan"},{"name":"Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan"},{"name":"Post Baccalaureate Medicine, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8496-1313","authenticated-orcid":false,"given":"Hsin-Yu","family":"Ho","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ching","family":"Chuang","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Sheng","family":"Lo","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9726-3234","authenticated-orcid":false,"given":"Ming-Ju","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan"},{"name":"Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan"},{"name":"Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan"},{"name":"Post Baccalaureate Medicine, National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu-Kuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.biopha.2016.09.082","article-title":"Role of oral microbiome on oral cancers, a review","volume":"84","author":"Gholizadeh","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.oraloncology.2015.01.001","article-title":"Life expectancy and expected years of life lost to oral cancer in Taiwan: A nation-wide analysis of 22,024 cases followed for 10 years","volume":"51","author":"Huang","year":"2015","journal-title":"Oral Oncol."},{"key":"ref_3","first-page":"303","article-title":"Screening for oral cancer","volume":"11","author":"Jitender","year":"2016","journal-title":"J. Exp. Ther. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.phymed.2012.10.017","article-title":"Antifilarial diarylheptanoids from Alnus nepalensis leaves growing in high altitude areas of Uttarakhand, India","volume":"20","author":"Yadav","year":"2013","journal-title":"Phytomedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s12272-017-0905-2","article-title":"Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway","volume":"40","author":"Dong","year":"2017","journal-title":"Arch. Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Ryu, M., Sung, C.K., Im, Y.J., and Chun, C. (2020). Activation of JNK and p38 in MCF-7 Cells and the In Vitro Anticancer Activity of Alnus hirsuta Extract. Molecules, 25.","DOI":"10.3390\/molecules25051073"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1055\/s-0032-1328301","article-title":"Diarylheptanoids from Alnus glutinosa bark and their chemoprotective effect on human lymphocytes DNA","volume":"79","author":"Novakovic","year":"2013","journal-title":"Planta Med."},{"key":"ref_8","first-page":"83","article-title":"Anti-oxidant and Anti-Inflammatory Cyclic Diarylheptanoids from Alnus japonica Stem Bark","volume":"16","author":"Ibrahim","year":"2017","journal-title":"Iran J. Pharm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/cbin.11137","article-title":"Cell death: A review of the major forms of apoptosis, necrosis and autophagy","volume":"43","year":"2019","journal-title":"Cell Biol. Int."},{"key":"ref_10","first-page":"3","article-title":"Apoptosis, oncosis, and necrosis. An overview of cell death","volume":"146","author":"Majno","year":"1995","journal-title":"Am. J. Pathol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1016\/j.phymed.2016.09.004","article-title":"Polyphyllin G induces apoptosis and autophagy cell death in human oral cancer cells","volume":"23","author":"Hsieh","year":"2016","journal-title":"Phytomedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/s41573-019-0036-1","article-title":"Lysosomes as a therapeutic target","volume":"18","author":"Bonam","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Bonam, S.R., Bayry, J., Tschan, M.P., and Muller, S. (2020). Progress and Challenges in The Use of MAP1LC3 as a Legitimate Marker for Measuring Dynamic Autophagy In Vivo. Cells, 9.","DOI":"10.3390\/cells9051321"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1590\/0001-3765201620160127","article-title":"The Complex Link between Apoptosis and Autophagy: A Promising New Role for RB","volume":"88","author":"Delou","year":"2016","journal-title":"An. Acad. Bras. Cienc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102735","DOI":"10.1155\/2013\/102735","article-title":"Role of the Crosstalk between Autophagy and Apoptosis in Cancer","volume":"2013","author":"Su","year":"2013","journal-title":"J. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1038\/sj.cdd.4401765","article-title":"Autophagy: Molecular machinery for self-eating","volume":"12","author":"Yorimitsu","year":"2005","journal-title":"Cell Death Differ."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e3089","DOI":"10.1038\/cddis.2017.459","article-title":"Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells","volume":"8","author":"Hsin","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e00199","DOI":"10.1042\/BSR20140141","article-title":"MAPK\/JNK signalling: A potential autophagy regulation pathway","volume":"35","author":"Zhou","year":"2015","journal-title":"Biosci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Song, F., Wang, Y., Jiang, D., Wang, T., Zhang, Y., Ma, H., and Kang, Y. (2016). Cyclic Compressive Stress Regulates Apoptosis in Rat Osteoblasts: Involvement of PI3K\/Akt and JNK MAPK Signaling Pathways. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165845"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1158\/1055-9965.EPI-18-1033","article-title":"Acrolein Is Involved in the Synergistic Potential of Cigarette Smoking- and Betel Quid Chewing-Related Human Oral Cancer","volume":"28","author":"Tsou","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hung, L.C., Kung, P.T., Lung, C.H., Tsai, M.H., Liu, S.A., Chiu, L.T., Huang, K.H., and Tsai, W.C. (2020). Assessment of the Risk of Oral Cancer Incidence in A High-Risk Population and Establishment of A Predictive Model for Oral Cancer Incidence Using A Population-Based Cohort in Taiwan. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17020665"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1172\/JCI129497","article-title":"HPV16 drives cancer immune escape via NLRX1-mediated degradation of STING","volume":"130","author":"Luo","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000485322","article-title":"High-Risk Human Papillomavirus in Oral Cancer: Clinical Implications","volume":"94","author":"Yete","year":"2018","journal-title":"Oncology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/joim.13010","article-title":"A global epidemic increase of an HPV-induced tonsil and tongue base cancer\u2014potential benefit from a pan-gender use of HPV vaccine","volume":"287","author":"Nasman","year":"2020","journal-title":"J. Intern. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Tumban, E. (2019). A Current Update on Human Papillomavirus-Associated Head and Neck Cancers. Viruses, 11.","DOI":"10.3390\/v11100922"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jfma.2018.03.013","article-title":"Prevalence of current oral HPV infection among 100 betel nut chewers or cigarette smokers in Northern Taiwan","volume":"118","author":"Wang","year":"2019","journal-title":"J. Formos Med. Assoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.antiviral.2016.03.016","article-title":"Gardasil-9: A global survey of projected efficacy","volume":"130","author":"Zhai","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_29","first-page":"4981","article-title":"Diarylheptanoids derived from Alpinia officinarum induce apoptosis, S-phase arrest and differentiation in human neuroblastoma cells","volume":"29","author":"Tabata","year":"2009","journal-title":"Anticancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1002\/(SICI)1097-0215(19971114)73:4<551::AID-IJC16>3.0.CO;2-C","article-title":"Altered expression and activity of G1\/S cyclins and cyclin-dependent kinases characterize squamous cell carcinomas of the head and neck","volume":"73","author":"Patel","year":"1997","journal-title":"Int. J. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.phrs.2019.04.001","article-title":"Plant lectins in cancer therapeutics: Targeting apoptosis and autophagy-dependent cell death","volume":"144","author":"Bhutia","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s12272-020-01239-w","article-title":"Role of autophagy in regulation of cancer cell death\/apoptosis during anti-cancer therapy: Focus on autophagy flux blockade","volume":"43","author":"Jang","year":"2020","journal-title":"Arch. Pharm. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.18388\/pb.2018_121","article-title":"The role of autophagy in cancer\u2014characterization of crosstalk between apoptosis and autophagy; autophagy as a new therapeutic strategy in glioblastoma","volume":"64","author":"Ciechomska","year":"2018","journal-title":"Postepy Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/tox.22568","article-title":"Curcuminoids combined with gefitinib mediated apoptosis and autophagy of human oral cancer SAS cells in vitro and reduced tumor of SAS cell xenograft mice in vivo","volume":"33","author":"Hsiao","year":"2018","journal-title":"Environ. Toxicol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/tox.22769","article-title":"Ursolic acid induces apoptosis and autophagy in oral cancer cells","volume":"34","author":"Lin","year":"2019","journal-title":"Environ. Toxicol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"111362","DOI":"10.1016\/j.biopha.2021.111362","article-title":"Apoptotic effects of dehydrocrenatidine via JNK and ERK pathway regulation in oral squamous cell carcinoma","volume":"137","author":"Ho","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chen, J.M., Chen, P.Y., Lin, C.C., Hsieh, M.C., and Lin, J.T. (2020). Antimetastatic Effects of Sesamin on Human Head and Neck Squamous Cell Carcinoma through Regulation of Matrix Metalloproteinase-2. Molecules, 25.","DOI":"10.3390\/molecules25092248"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1007\/s00204-017-1973-2","article-title":"Erratum to: Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K\/Akt and ERK and JNK signaling pathways in human lung cancer cell lines","volume":"91","author":"Hsieh","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrc2694","article-title":"Signal integration by JNK and p38 MAPK pathways in cancer development","volume":"9","author":"Wagner","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"600","DOI":"10.3109\/10799893.2015.1030412","article-title":"Signaling pathway of MAPK\/ERK in cell proliferation, differentiation, migration, senescence and apoptosis","volume":"35","author":"Sun","year":"2015","journal-title":"J. Recept Signal Transduct Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4211\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:49:40Z","timestamp":1760161780000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/8\/4211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,19]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["ijms22084211"],"URL":"https:\/\/doi.org\/10.3390\/ijms22084211","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,19]]}}}