{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T05:41:05Z","timestamp":1792561265348,"version":"4.5.0"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":89,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC-110-2314-B-341-004"],"award-info":[{"award-number":["NSTC-110-2314-B-341-004"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC-111-2314-B-341-004"],"award-info":[{"award-number":["NSTC-111-2314-B-341-004"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC-110-2314-B-341-001-MY2"],"award-info":[{"award-number":["NSTC-110-2314-B-341-001-MY2"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004319","name":"Shin Kong Wu Ho-Su Memorial Hospital","doi-asserted-by":"publisher","award":["2022SKHBDR001"],"award-info":[{"award-number":["2022SKHBDR001"]}],"id":[{"id":"10.13039\/501100004319","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["TMU113-AE1-B37"],"award-info":[{"award-number":["TMU113-AE1-B37"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Cell Int"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bladder cancer (BLCA) is the second most common malignant cancer of the male urological system. BLCA is characterized by a high rate of recurrence. Capsaicin is increasingly being used in cancer treatment. This study analyzed the inhibitory effects of capsaicin on cell invasiveness and examined whether capsaicin enhances the chemosensitivity of BLCA. High concentrations of capsaicin induced apoptosis in cancer cells. Co-administration of capsaicin with various chemotherapy drugs (cisplatin, epirubicin, and mitomycin C) increased cancer cell sensitivity to chemotherapy. At lower concentrations, capsaicin effectively inhibited cell invasiveness by downregulating MMP11 expression. Mechanistically, capsaicin suppressed MMP11 expression through the transient receptor potential vanilloid 1 receptor and the p38\/extracellular signal-regulated kinase\/c-Jun signaling pathway. Functional analysis revealed a positive correlation between the expression level of MMP11 and various ontogenetic properties of BLCA. MMP11 expression was positively correlated with clinical staging, muscle-invasive bladder cancer, lymphatic metastasis, and poor prognosis in patients with BLCA. These findings suggest that MMP11 has potential as a clinical prognostic marker for BLCA. Finally, capsaicin demonstrated significant tumor growth suppression and enhanced chemosensitivity in vivo. Taken together, capsaicin may promote apoptosis, inhibit cell invasion in vitro, and suppress tumor growth in vivo. Combining capsaicin with first-line chemotherapeutic drugs may enhance their efficacy against BLCA, and therefore, which indicates that capsaicin has promise as a clinical medication.<\/jats:p>","DOI":"10.1186\/s12935-026-04397-x","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:45:36Z","timestamp":1784900736000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Capsaicin enhances chemosensitivity and mitigates MMP11-driven aggressiveness in human bladder cancer"],"prefix":"10.1186","volume":"26","author":[{"given":"Te-Fu","family":"Tsai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao-Chiun","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-You","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Win-Ping","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas I-Sheng","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuang-Yu","family":"Chou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yen","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-En","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Hsin","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Wei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-Chen","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"issue":"1","key":"4397_CR1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.eururo.2016.06.010","volume":"71","author":"S Antoni","year":"2017","unstructured":"Antoni S, et al. Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur Urol. 2017;71(1):96\u2013108.","journal-title":"Eur Urol"},{"issue":"17","key":"4397_CR2","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1002\/cncr.28147","volume":"119","author":"K Chamie","year":"2013","unstructured":"Chamie K, et al. Recurrence of high-risk bladder cancer: a population-based analysis. Cancer. 2013;119(17):3219\u201327.","journal-title":"Cancer"},{"issue":"1","key":"4397_CR3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.5489\/cuaj.777","volume":"4","author":"S Aldousari","year":"2010","unstructured":"Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer. Can Urol Assoc J. 2010;4(1):56\u201364.","journal-title":"Can Urol Assoc J"},{"issue":"12","key":"4397_CR4","doi-asserted-by":"publisher","first-page":"3145","DOI":"10.1007\/s11255-022-03339-6","volume":"54","author":"N van Ginkel","year":"2022","unstructured":"van Ginkel N, et al. Survival outcomes of patients with muscle-invasive bladder cancer according to pathological response at radical cystectomy with or without neo-adjuvant chemotherapy: a case-control matching study. Int Urol Nephrol. 2022;54(12):3145\u201352.","journal-title":"Int Urol Nephrol"},{"issue":"5","key":"4397_CR5","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.3390\/curroncol28050325","volume":"28","author":"A Beigi","year":"2021","unstructured":"Beigi A, et al. Survival Outcomes Associated with First and Second-Line Palliative Systemic Therapies in Patients with Metastatic Bladder Cancer. Curr Oncol. 2021;28(5):3812\u201324.","journal-title":"Curr Oncol"},{"key":"4397_CR6","doi-asserted-by":"crossref","unstructured":"Cabral-Pacheco GA et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci, 2020. 21(24):9739.","DOI":"10.3390\/ijms21249739"},{"key":"4397_CR7","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.3389\/fonc.2019.01370","volume":"9","author":"S Quintero-Fabian","year":"2019","unstructured":"Quintero-Fabian S, et al. Role of Matrix Metalloproteinases in Angiogenesis and Cancer. Front Oncol. 2019;9:1370.","journal-title":"Front Oncol"},{"issue":"3","key":"4397_CR8","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/nrm2125","volume":"8","author":"A Page-McCaw","year":"2007","unstructured":"Page-McCaw A, Ewald AJ, Werb Z. Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 2007;8(3):221\u201333.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"4","key":"4397_CR9","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1089\/wound.2014.0581","volume":"4","author":"MP Caley","year":"2015","unstructured":"Caley MP, Martins VL, O\u2019Toole EA. Metalloproteinases and Wound Healing. Adv Wound Care (New Rochelle). 2015;4(4):225\u201334.","journal-title":"Adv Wound Care (New Rochelle)"},{"key":"4397_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.critrevonc.2019.02.010","volume":"137","author":"G Gonzalez-Avila","year":"2019","unstructured":"Gonzalez-Avila G, et al. Matrix metalloproteinases participation in the metastatic process and their diagnostic and therapeutic applications in cancer. Crit Rev Oncol Hematol. 2019;137:57\u201383.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"5","key":"4397_CR11","doi-asserted-by":"publisher","first-page":"3979","DOI":"10.1002\/jcp.30150","volume":"236","author":"SW Wang","year":"2021","unstructured":"Wang SW, et al. Melatonin impedes prostate cancer metastasis by suppressing MMP-13 expression. J Cell Physiol. 2021;236(5):3979\u201390.","journal-title":"J Cell Physiol"},{"key":"4397_CR12","doi-asserted-by":"publisher","first-page":"115540","DOI":"10.1016\/j.bcp.2023.115540","volume":"211","author":"WC Chen","year":"2023","unstructured":"Chen WC, et al. Bone sialoprotein promotes lung cancer osteolytic bone metastasis via MMP14-dependent mechanisms. Biochem Pharmacol. 2023;211:115540.","journal-title":"Biochem Pharmacol"},{"issue":"5","key":"4397_CR13","doi-asserted-by":"publisher","first-page":"e0252052","DOI":"10.1371\/journal.pone.0252052","volume":"16","author":"HS Kim","year":"2021","unstructured":"Kim HS, et al. High MMP-11 expression associated with low CD8\u2009+\u2009T cells decreases the survival rate in patients with breast cancer. PLoS ONE. 2021;16(5):e0252052.","journal-title":"PLoS ONE"},{"key":"4397_CR14","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.omto.2019.03.012","volume":"14","author":"H Yang","year":"2019","unstructured":"Yang H, et al. Matrix Metalloproteinase 11 Is a Potential Therapeutic Target in Lung Adenocarcinoma. Mol Ther Oncolytics. 2019;14:82\u201393.","journal-title":"Mol Ther Oncolytics"},{"issue":"4","key":"4397_CR15","doi-asserted-by":"publisher","first-page":"599","DOI":"10.3233\/CBM-160601","volume":"16","author":"L Pang","year":"2016","unstructured":"Pang L, et al. Elevated serum levels of MMP-11 correlate with poor prognosis in colon cancer patients. Cancer Biomark. 2016;16(4):599\u2013607.","journal-title":"Cancer Biomark"},{"issue":"2","key":"4397_CR16","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.bbrc.2004.11.027","volume":"326","author":"H Deng","year":"2005","unstructured":"Deng H, et al. Matrix metalloproteinase 11 depletion inhibits cell proliferation in gastric cancer cells. Biochem Biophys Res Commun. 2005;326(2):274\u201381.","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"4397_CR17","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1016\/j.biocel.2007.05.023","volume":"39","author":"L Jia","year":"2007","unstructured":"Jia L, et al. siRNA targeted against matrix metalloproteinase 11 inhibits the metastatic capability of murine hepatocarcinoma cell Hca-F to lymph nodes. Int J Biochem Cell Biol. 2007;39(11):2049\u201362.","journal-title":"Int J Biochem Cell Biol"},{"issue":"8\u20139","key":"4397_CR18","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/S0945-053X(97)90028-7","volume":"15","author":"P Basset","year":"1997","unstructured":"Basset P, et al. Matrix metalloproteinases as stromal effectors of human carcinoma progression: therapeutic implications. Matrix Biol. 1997;15(8\u20139):535\u201341.","journal-title":"Matrix Biol"},{"issue":"8","key":"4397_CR19","doi-asserted-by":"publisher","first-page":"2832","DOI":"10.1158\/1078-0432.CCR-1157-03","volume":"10","author":"LE Jones","year":"2004","unstructured":"Jones LE, et al. Comprehensive analysis of matrix metalloproteinase and tissue inhibitor expression in pancreatic cancer: increased expression of matrix metalloproteinase-7 predicts poor survival. Clin Cancer Res. 2004;10(8):2832\u201345.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"4397_CR20","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1097\/00019606-199612000-00010","volume":"5","author":"M Thewes","year":"1996","unstructured":"Thewes M, et al. Stromelysin-3 (ST-3) mRNA expression in colorectal carcinomas. Localization and clinicopathologic correlations. Diagn Mol Pathol. 1996;5(4):284\u201390.","journal-title":"Diagn Mol Pathol"},{"key":"4397_CR21","doi-asserted-by":"crossref","unstructured":"Hsieh CY et al. Impact of Matrix Metalloproteinase-11 Gene Polymorphisms on Biochemical Recurrence and Clinicopathological Characteristics of Prostate Cancer. Int J Environ Res Public Health, 2020. 17(22):8603.","DOI":"10.3390\/ijerph17228603"},{"key":"4397_CR22","doi-asserted-by":"crossref","unstructured":"Chapa-Oliver AM, Mejia-Teniente L. Capsaicin: From Plants to a Cancer-Suppressing Agent. Molecules, 2016. 21(8):931.","DOI":"10.3390\/molecules21080931"},{"issue":"3","key":"4397_CR23","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1093\/pm\/pnv068","volume":"17","author":"M Wallace","year":"2016","unstructured":"Wallace M, et al. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study of the T-Type Calcium Channel Blocker ABT-639 in an Intradermal Capsaicin Experimental Pain Model in Healthy Adults. Pain Med. 2016;17(3):551\u201360.","journal-title":"Pain Med"},{"issue":"12","key":"4397_CR24","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1016\/j.jpain.2008.05.013","volume":"9","author":"H Wang","year":"2008","unstructured":"Wang H, et al. Effect of morphine and pregabalin compared with diphenhydramine hydrochloride and placebo on hyperalgesia and allodynia induced by intradermal capsaicin in healthy male subjects. J Pain. 2008;9(12):1088\u201395.","journal-title":"J Pain"},{"issue":"25","key":"4397_CR25","doi-asserted-by":"publisher","first-page":"7396","DOI":"10.1021\/jf020431w","volume":"50","author":"A Rosa","year":"2002","unstructured":"Rosa A, et al. Antioxidant activity of capsinoids. J Agric Food Chem. 2002;50(25):7396\u2013401.","journal-title":"J Agric Food Chem"},{"issue":"3","key":"4397_CR26","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/S0898-6568(02)00086-4","volume":"15","author":"CS Kim","year":"2003","unstructured":"Kim CS, et al. Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages. Cell Signal. 2003;15(3):299\u2013306.","journal-title":"Cell Signal"},{"key":"4397_CR27","doi-asserted-by":"crossref","unstructured":"Zheng J et al. Dietary capsaicin and its anti-obesity potency: from mechanism to clinical implications. Biosci Rep, 2017. 37(3):BSR20170286.","DOI":"10.1042\/BSR20170286"},{"issue":"6653","key":"4397_CR28","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1038\/39807","volume":"389","author":"MJ Caterina","year":"1997","unstructured":"Caterina MJ, et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997;389(6653):816\u201324.","journal-title":"Nature"},{"issue":"2","key":"4397_CR29","doi-asserted-by":"publisher","first-page":"517","DOI":"10.3390\/cells3020517","volume":"3","author":"R Brito","year":"2014","unstructured":"Brito R, et al. TRPV1: A Potential Drug Target for Treating Various Diseases. Cells. 2014;3(2):517\u201345.","journal-title":"Cells"},{"issue":"3","key":"4397_CR30","first-page":"837","volume":"36","author":"R Clark","year":"2016","unstructured":"Clark R, Lee SH. Anticancer Properties of Capsaicin Against Human Cancer. Anticancer Res. 2016;36(3):837\u201343.","journal-title":"Anticancer Res"},{"issue":"1","key":"4397_CR31","doi-asserted-by":"publisher","first-page":"53","DOI":"10.4103\/0019-509X.58860","volume":"47","author":"AA Oyagbemi","year":"2010","unstructured":"Oyagbemi AA, Saba AB, Azeez OI. Capsaicin: a novel chemopreventive molecule and its underlying molecular mechanisms of action. Indian J Cancer. 2010;47(1):53\u20138.","journal-title":"Indian J Cancer"},{"issue":"5","key":"4397_CR32","doi-asserted-by":"publisher","first-page":"e0121538","DOI":"10.1371\/journal.pone.0121538","volume":"10","author":"ZF Hong","year":"2015","unstructured":"Hong ZF, et al. Capsaicin Enhances the Drug Sensitivity of Cholangiocarcinoma through the Inhibition of Chemotherapeutic-Induced Autophagy. PLoS ONE. 2015;10(5):e0121538.","journal-title":"PLoS ONE"},{"issue":"3","key":"4397_CR33","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/0885-3924(94)00130-D","volume":"10","author":"A Berger","year":"1995","unstructured":"Berger A, et al. Oral capsaicin provides temporary relief for oral mucositis pain secondary to chemotherapy\/radiation therapy. J Pain Symptom Manage. 1995;10(3):243\u20138.","journal-title":"J Pain Symptom Manage"},{"issue":"8","key":"4397_CR34","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.1200\/JCO.1997.15.8.2974","volume":"15","author":"N Ellison","year":"1997","unstructured":"Ellison N, et al. Phase III placebo-controlled trial of capsaicin cream in the management of surgical neuropathic pain in cancer patients. J Clin Oncol. 1997;15(8):2974\u201380.","journal-title":"J Clin Oncol"},{"issue":"2","key":"4397_CR35","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1002\/tox.23024","volume":"36","author":"CY Ho","year":"2021","unstructured":"Ho CY, et al. Miconazole induces protective autophagy in bladder cancer cells. Environ Toxicol. 2021;36(2):185\u201393.","journal-title":"Environ Toxicol"},{"issue":"13","key":"4397_CR36","doi-asserted-by":"publisher","first-page":"6046","DOI":"10.1111\/jcmm.16463","volume":"25","author":"KY Chou","year":"2021","unstructured":"Chou KY, et al. Thrombospondin-4 promotes bladder cancer cell migration and invasion via MMP2 production. J Cell Mol Med. 2021;25(13):6046\u201355.","journal-title":"J Cell Mol Med"},{"issue":"4","key":"4397_CR37","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1038\/s41419-022-04791-z","volume":"13","author":"TI Hwang","year":"2022","unstructured":"Hwang TI, et al. Hsa-miR-30a-3p overcomes the acquired protective autophagy of bladder cancer in chemotherapy and suppresses tumor growth and muscle invasion. Cell Death Dis. 2022;13(4):390.","journal-title":"Cell Death Dis"},{"issue":"50","key":"4397_CR38","doi-asserted-by":"publisher","first-page":"87684","DOI":"10.18632\/oncotarget.21196","volume":"8","author":"A Bort","year":"2017","unstructured":"Bort A, et al. Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation. Oncotarget. 2017;8(50):87684\u201398.","journal-title":"Oncotarget"},{"issue":"1","key":"4397_CR39","doi-asserted-by":"publisher","first-page":"9617","DOI":"10.1038\/s41598-023-36774-1","volume":"13","author":"TM Steele","year":"2023","unstructured":"Steele TM, et al. Cisplatin-induced increase in heregulin 1 and its attenuation by the monoclonal ErbB3 antibody seribantumab in bladder cancer. Sci Rep. 2023;13(1):9617.","journal-title":"Sci Rep"},{"issue":"2","key":"4397_CR40","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/sj.cdd.4400476","volume":"6","author":"AG Porter","year":"1999","unstructured":"Porter AG, Janicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 1999;6(2):99\u2013104.","journal-title":"Cell Death Differ"},{"issue":"1","key":"4397_CR41","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1093\/toxsci\/kfs142","volume":"128","author":"F Zhang","year":"2012","unstructured":"Zhang F, Lau SS, Monks TJ. A dual role for poly(ADP-ribose) polymerase-1 during caspase-dependent apoptosis. Toxicol Sci. 2012;128(1):103\u201314.","journal-title":"Toxicol Sci"},{"key":"4397_CR42","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3389\/fphar.2018.00245","volume":"9","author":"K Nurgali","year":"2018","unstructured":"Nurgali K, Jagoe RT, Abalo R. Editorial: Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae? Front Pharmacol. 2018;9:245.","journal-title":"Front Pharmacol"},{"issue":"4","key":"4397_CR43","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/S1470-2045(04)01431-7","volume":"5","author":"F Entschladen","year":"2004","unstructured":"Entschladen F, et al. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters. Lancet Oncol. 2004;5(4):254\u20138.","journal-title":"Lancet Oncol"},{"issue":"Suppl 3","key":"4397_CR44","doi-asserted-by":"publisher","first-page":"S433","DOI":"10.1245\/s10434-012-2734-3","volume":"20","author":"KW Min","year":"2013","unstructured":"Min KW, et al. Diagnostic and prognostic relevance of MMP-11 expression in the stromal fibroblast-like cells adjacent to invasive ductal carcinoma of the breast. Ann Surg Oncol. 2013;20(Suppl 3):S433\u201342.","journal-title":"Ann Surg Oncol"},{"issue":"11","key":"4397_CR45","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.7150\/ijms.98007","volume":"21","author":"C Pan","year":"2024","unstructured":"Pan C, et al. Matrix Metalloproteinase 11 Promotes Migration and Invasion of Colorectal Cancer by Elevating Slug Protein. Int J Med Sci. 2024;21(11):2170\u201388.","journal-title":"Int J Med Sci"},{"issue":"1","key":"4397_CR46","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/S0021-5198(19)30622-5","volume":"83","author":"M Tominaga","year":"2000","unstructured":"Tominaga M, Julius D. Capsaicin receptor in the pain pathway. Jpn J Pharmacol. 2000;83(1):20\u20134.","journal-title":"Jpn J Pharmacol"},{"key":"4397_CR47","doi-asserted-by":"crossref","unstructured":"Chen M et al. Mitogen-Activated Protein Kinase and Intracellular Polyamine Signaling Is Involved in TRPV1 Activation-Induced Cardiac Hypertrophy. J Am Heart Assoc, 2016. 5(8):e003718.","DOI":"10.1161\/JAHA.116.003718"},{"issue":"3","key":"4397_CR48","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1093\/cvr\/cvr104","volume":"91","author":"LC Ching","year":"2011","unstructured":"Ching LC, et al. Molecular mechanisms of activation of endothelial nitric oxide synthase mediated by transient receptor potential vanilloid type 1. Cardiovasc Res. 2011;91(3):492\u2013501.","journal-title":"Cardiovasc Res"},{"key":"4397_CR49","doi-asserted-by":"publisher","first-page":"684516","DOI":"10.3389\/fcell.2021.684516","volume":"9","author":"Y Liu","year":"2021","unstructured":"Liu Y, et al. TRPV1 Antagonist Prevents Neonatal Sevoflurane-Induced Synaptic Abnormality and Cognitive Impairment in Mice Through Regulating the Src\/Cofilin Signaling Pathway. Front Cell Dev Biol. 2021;9:684516.","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"4397_CR50","first-page":"23","volume":"38","author":"LD Moore","year":"2013","unstructured":"Moore LD, Le T, Fan G. DNA methylation its basic function Neuropsychopharmacol. 2013;38(1):23\u201338.","journal-title":"DNA methylation its basic function Neuropsychopharmacol"},{"issue":"1\u20132","key":"4397_CR51","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1007\/s12307-014-0146-6","volume":"7","author":"S Pal","year":"2014","unstructured":"Pal S, et al. Extracellular matrix protein laminin induces matrix metalloproteinase-9 in human breast cancer cell line mcf-7. Cancer Microenviron. 2014;7(1\u20132):71\u20138.","journal-title":"Cancer Microenviron"},{"issue":"10","key":"4397_CR52","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1016\/j.biochi.2010.07.005","volume":"92","author":"T Sen","year":"2010","unstructured":"Sen T, et al. Fibronectin induces matrix metalloproteinase-9 (MMP-9) in human laryngeal carcinoma cells by involving multiple signaling pathways. Biochimie. 2010;92(10):1422\u201334.","journal-title":"Biochimie"},{"issue":"4","key":"4397_CR53","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.matbio.2006.10.014","volume":"26","author":"K Borrirukwanit","year":"2007","unstructured":"Borrirukwanit K, et al. The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by alphaVbeta3 integrin in human breast cancer cells. Matrix Biol. 2007;26(4):291\u2013305.","journal-title":"Matrix Biol"},{"key":"4397_CR54","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s40169-015-0048-3","volume":"4","author":"S Heerboth","year":"2015","unstructured":"Heerboth S, et al. EMT and tumor metastasis. Clin Transl Med. 2015;4:6.","journal-title":"Clin Transl Med"},{"issue":"3","key":"4397_CR55","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1021\/acs.jmedchem.0c01679","volume":"64","author":"SD Richbart","year":"2021","unstructured":"Richbart SD, et al. Nonpungent N-AVAM Capsaicin Analogues and Cancer Therapy. J Med Chem. 2021;64(3):1346\u201361.","journal-title":"J Med Chem"},{"issue":"13","key":"4397_CR56","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.lfs.2005.07.019","volume":"78","author":"Tuoya","year":"2006","unstructured":"Tuoya, et al. Apoptosis induction by dohevanil, a DHA substitutive analog of capsaicin, in MCF-7 cells. Life Sci. 2006;78(13):1515\u20139.","journal-title":"Life Sci"},{"issue":"13","key":"4397_CR57","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.1016\/j.bmc.2019.05.020","volume":"27","author":"GJV Pereira","year":"2019","unstructured":"Pereira GJV, et al. Capsaicin-like analogue induced selective apoptosis in A2058 melanoma cells: Design, synthesis and molecular modeling. Bioorg Med Chem. 2019;27(13):2893\u2013904.","journal-title":"Bioorg Med Chem"},{"issue":"3","key":"4397_CR58","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1124\/jpet.117.243691","volume":"364","author":"JR Friedman","year":"2018","unstructured":"Friedman JR, et al. Anticancer Activity of Natural and Synthetic Capsaicin Analogs. J Pharmacol Exp Ther. 2018;364(3):462\u201373.","journal-title":"J Pharmacol Exp Ther"},{"issue":"7","key":"4397_CR59","doi-asserted-by":"publisher","first-page":"4294","DOI":"10.1021\/acs.jmedchem.2c01594","volume":"66","author":"KC Brown","year":"2023","unstructured":"Brown KC, et al. Anticancer Activity of Region B Capsaicin Analogs. J Med Chem. 2023;66(7):4294\u2013323.","journal-title":"J Med Chem"},{"issue":"1","key":"4397_CR60","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s00394-003-0394-6","volume":"42","author":"A Macho","year":"2003","unstructured":"Macho A, et al. Non-pungent capsaicinoids from sweet pepper synthesis and evaluation of the chemopreventive and anticancer potential. Eur J Nutr. 2003;42(1):2\u20139.","journal-title":"Eur J Nutr"},{"key":"4397_CR61","doi-asserted-by":"publisher","first-page":"102870","DOI":"10.1016\/j.ceca.2024.102870","volume":"119","author":"TKE Maximiano","year":"2024","unstructured":"Maximiano TKE, et al. TRPV1: Receptor structure, activation, modulation and role in neuro-immune interactions and pain. Cell Calcium. 2024;119:102870.","journal-title":"Cell Calcium"},{"key":"4397_CR62","doi-asserted-by":"crossref","unstructured":"Negri S et al. Endothelial TRPV1 as an Emerging Molecular Target to Promote Therapeutic Angiogenesis. Cells, 2020. 9(6):1341.","DOI":"10.3390\/cells9061341"},{"key":"4397_CR63","doi-asserted-by":"crossref","unstructured":"Fattori V et al. Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. Molecules, 2016. 21(7):844.","DOI":"10.3390\/molecules21070844"},{"issue":"6","key":"4397_CR64","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1016\/j.thromres.2009.05.001","volume":"124","author":"MJ Adams","year":"2009","unstructured":"Adams MJ, Ahuja KD, Geraghty DP. Effect of capsaicin and dihydrocapsaicin on in vitro blood coagulation and platelet aggregation. Thromb Res. 2009;124(6):721\u20133.","journal-title":"Thromb Res"},{"key":"4397_CR65","doi-asserted-by":"crossref","unstructured":"Sun F, Xiong S, Zhu Z. Dietary Capsaicin Protects Cardiometabolic Organs Dysfunct Nutrients, 2016. 8(5):174.","DOI":"10.3390\/nu8050174"},{"key":"4397_CR66","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.3389\/fonc.2019.01087","volume":"9","author":"JK Bujak","year":"2019","unstructured":"Bujak JK, et al. Inflammation, Cancer and Immunity-Implication of TRPV1 Channel. Front Oncol. 2019;9:1087.","journal-title":"Front Oncol"},{"issue":"1","key":"4397_CR67","doi-asserted-by":"publisher","first-page":"881","DOI":"10.3892\/mmr.2015.4623","volume":"13","author":"L Zheng","year":"2016","unstructured":"Zheng L, et al. Capsaicin enhances anti-proliferation efficacy of pirarubicin via activating TRPV1 and inhibiting PCNA nuclear translocation in 5637 cells. Mol Med Rep. 2016;13(1):881\u20137.","journal-title":"Mol Med Rep"},{"issue":"19","key":"4397_CR68","doi-asserted-by":"publisher","first-page":"5678","DOI":"10.7150\/jca.45918","volume":"11","author":"L Zheng","year":"2020","unstructured":"Zheng L, et al. TRPV1 acts as a Tumor Suppressor and is associated with Immune Cell Infiltration in Clear Cell Renal Cell Carcinoma: evidence from integrated analysis. J Cancer. 2020;11(19):5678\u201388.","journal-title":"J Cancer"},{"key":"4397_CR69","doi-asserted-by":"crossref","unstructured":"Nie R, Liu Q, Wang X. TRPV1 Is a Potential Tumor Suppressor for Its Negative Association with Tumor Proliferation and Positive Association with Antitumor Immune Responses in Pan-Cancer. J Oncol, 2022. 2022: p. 6964550.","DOI":"10.1155\/2022\/6964550"},{"issue":"4","key":"4397_CR70","doi-asserted-by":"publisher","first-page":"332","DOI":"10.4048\/jbc.2014.17.4.332","volume":"17","author":"C Vercelli","year":"2014","unstructured":"Vercelli C, et al. Transient receptor potential vanilloid 1 expression and functionality in mcf-7 cells: a preliminary investigation. J Breast Cancer. 2014;17(4):332\u20138.","journal-title":"J Breast Cancer"},{"issue":"2","key":"4397_CR71","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ceca.2014.04.006","volume":"56","author":"TT Wu","year":"2014","unstructured":"Wu TT, et al. Consequences of activating the calcium-permeable ion channel TRPV1 in breast cancer cells with regulated TRPV1 expression. Cell Calcium. 2014;56(2):59\u201367.","journal-title":"Cell Calcium"},{"issue":"6","key":"4397_CR72","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1158\/1535-7163.MCT-17-0646","volume":"17","author":"A Winer","year":"2018","unstructured":"Winer A, Adams S, Mignatti P. Matrix Metalloproteinase Inhibitors in Cancer Therapy: Turning Past Failures Into Future Successes. Mol Cancer Ther. 2018;17(6):1147\u201355.","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"4397_CR73","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1423-0127-17-10","volume":"17","author":"AK Chaudhary","year":"2010","unstructured":"Chaudhary AK, et al. Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck. J Biomed Sci. 2010;17(1):10.","journal-title":"J Biomed Sci"},{"issue":"7","key":"4397_CR74","first-page":"1912","volume":"7","author":"NC Levitt","year":"2001","unstructured":"Levitt NC, et al. Phase I and pharmacological study of the oral matrix metalloproteinase inhibitor, MMI270 (CGS27023A), in patients with advanced solid cancer. Clin Cancer Res. 2001;7(7):1912\u201322.","journal-title":"Clin Cancer Res"},{"issue":"3","key":"4397_CR75","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1023\/A:1011183905848","volume":"12","author":"C Erlichman","year":"2001","unstructured":"Erlichman C, et al. Phase I study of the matrix metalloproteinase inhibitor, BAY 12-9566. Ann Oncol. 2001;12(3):389\u201395.","journal-title":"Ann Oncol"},{"issue":"Suppl 3","key":"4397_CR76","doi-asserted-by":"publisher","first-page":"iii62","DOI":"10.1136\/ard.60.90003.iii62","volume":"60","author":"DR Close","year":"2001","unstructured":"Close DR. Matrix metalloproteinase inhibitors in rheumatic diseases. Ann Rheum Dis. 2001;60(Suppl 3):iii62\u20137.","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"4397_CR77","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1039\/C7FO01295K","volume":"9","author":"S Xu","year":"2018","unstructured":"Xu S, et al. Capsaicin inhibits the metastasis of human papillary thyroid carcinoma BCPAP cells through the modulation of the TRPV1 channel. Food Funct. 2018;9(1):344\u201354.","journal-title":"Food Funct"},{"issue":"6","key":"4397_CR78","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1016\/S0093-7754(01)90035-1","volume":"28","author":"P Falardeau","year":"2001","unstructured":"Falardeau P, et al. Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001;28(6):620\u20135.","journal-title":"Semin Oncol"},{"issue":"3","key":"4397_CR79","first-page":"1997","volume":"19","author":"YJ Guo","year":"2020","unstructured":"Guo YJ, et al. ERK\/MAPK signalling pathway and tumorigenesis. Exp Ther Med. 2020;19(3):1997\u20132007.","journal-title":"Exp Ther Med"},{"issue":"41","key":"4397_CR80","doi-asserted-by":"publisher","first-page":"11673","DOI":"10.3748\/wjg.v21.i41.11673","volume":"21","author":"M Yang","year":"2015","unstructured":"Yang M, Huang CZ. Mitogen-activated protein kinase signaling pathway and invasion and metastasis of gastric cancer. World J Gastroenterol. 2015;21(41):11673\u20139.","journal-title":"World J Gastroenterol"},{"key":"4397_CR81","doi-asserted-by":"crossref","unstructured":"Braicu C et al. A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer. Cancers (Basel), 2019. 11(10):1618.","DOI":"10.3390\/cancers11101618"},{"issue":"1","key":"4397_CR82","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ygyno.2019.11.006","volume":"156","author":"I Vergote","year":"2020","unstructured":"Vergote I, et al. A randomized, double-blind, placebo-controlled phase 1b\/2 study of ralimetinib, a p38 MAPK inhibitor, plus gemcitabine and carboplatin versus gemcitabine and carboplatin for women with recurrent platinum-sensitive ovarian cancer. Gynecol Oncol. 2020;156(1):23\u201331.","journal-title":"Gynecol Oncol"},{"key":"4397_CR83","doi-asserted-by":"crossref","unstructured":"Phan T, et al. P38 kinase in gastrointestinal cancers. Cancer Gene Ther; 2023.","DOI":"10.1038\/s41417-023-00622-1"},{"issue":"10","key":"4397_CR84","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1158\/1535-7163.MCT-20-0909","volume":"20","author":"JM Munck","year":"2021","unstructured":"Munck JM, et al. ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK. Mol Cancer Ther. 2021;20(10):1757\u201368.","journal-title":"Mol Cancer Ther"}],"container-title":["Cancer Cell International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12935-026-04397-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04397-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12935-026-04397-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T05:02:24Z","timestamp":1792558944000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12935-026-04397-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":84,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4397"],"URL":"https:\/\/doi.org\/10.1186\/s12935-026-04397-x","relation":{},"ISSN":["1475-2867"],"issn-type":[{"value":"1475-2867","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"assertion":[{"value":"20 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were approved by the Institutional Animal Care and Use Committee of Shin Kong Wu Ho-Su Memorial Hospital (Approval No. 110SKH005) and were conducted in accordance with the institution\u2019s Guidelines for Animal Experimentation.","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"346"}}