{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T23:50:53Z","timestamp":1775260253764,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNR-DISBA project NutrAge","award":["nr. 7022"],"award-info":[{"award-number":["nr. 7022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Given the known pro-oxidant status of tumour cells, the development of anti-proliferative strategies focuses on products with both anti- and pro-oxidant properties that can enhance antitumour drug cytotoxicity. We used a C. zeylanicum essential oil (CINN-EO) and assessed its effect on a human metastatic melanoma cell line (M14). Human PBMCs and MDMs from healthy donors were used as normal control cells. CINN-EO induced cell growth inhibition, cell cycle perturbation, ROS and Fe(II) increases, and mitochondrial membrane depolarization. To assess whether CINN-EO could affect the stress response, we analysed iron metabolism and stress response gene expression. CINN-EO increased HMOX1, FTH1, SLC7A11, DGKK, and GSR expression but repressed OXR1, SOD3, Tf, and TfR1 expression. HMOX1, Fe(II), and ROS increases are associated with ferroptosis, which can be reversed by SnPPIX, an HMOX1 inhibitor. Indeed, our data demonstrated that SnPPIX significantly attenuated the inhibition of cell proliferation, suggesting that the inhibition of cell proliferation induced by CINN-EO could be related to ferroptosis. Concurrent treatment with CINN-EO enhanced the anti-melanoma effect of two conventional antineoplastic drugs: the mitochondria-targeting tamoxifen and the anti-BRAF dabrafenib. We demonstrate that CINN-EO-mediated induction of an incomplete stress response specifically in cancer cells affects the proliferation of melanoma cells and can enhance drug cytotoxicity.<\/jats:p>","DOI":"10.3390\/ijms24065698","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T03:33:57Z","timestamp":1679024037000},"page":"5698","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Cinnamomum zeylanicum Blume Essential Oil Inhibits Metastatic Melanoma Cell Proliferation by Triggering an Incomplete Tumour Cell Stress Response"],"prefix":"10.3390","volume":"24","author":[{"given":"Giulia","family":"Cappelli","sequence":"first","affiliation":[{"name":"Institute for Biological Systems (ISB)-CNR, Via Salaria Km 29, 00015 Monterotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Giovannini","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC)-CNR, Via E. Ramarini 32, 00015 Monterotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Vilardo","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies (ITB)-CNR, Via Fratelli Cervi 93, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Basso","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC)-CNR, Via E. Ramarini 32, 00015 Monterotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Iannetti","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC)-CNR, Via E. Ramarini 32, 00015 Monterotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianna","family":"Massa","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Cell Biology (IBBC)-CNR, Via E. Ramarini 32, 00015 Monterotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6610-6110","authenticated-orcid":false,"given":"Giuseppe","family":"Ruberto","sequence":"additional","affiliation":[{"name":"Institute for Biochemical Chemistry (ICB)-CNR, Via Paolo Gaifami, 18, 95126 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, UCSF Byers Hall MC2552, San Francisco, CA 94158, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Pastore","sequence":"additional","affiliation":[{"name":"Sanatrix Clinic, Via di Trasone 61, 00199 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2646-9224","authenticated-orcid":false,"given":"Igea","family":"D\u2019Agnano","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies (ITB)-CNR, Via Fratelli Cervi 93, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5616-6566","authenticated-orcid":false,"given":"Francesca","family":"Mariani","sequence":"additional","affiliation":[{"name":"Institute for Biological Systems (ISB)-CNR, Via Salaria Km 29, 00015 Monterotondo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"ref_1","unstructured":"Heistein, J.B., Acharya, U., and Mukkamalla, S.K.R. 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