{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:41:55Z","timestamp":1783586515709,"version":"3.55.0"},"reference-count":99,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007771","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["PCN-2-043\/N\/0\/F, PCN-1-097\/K\/0\/F"],"award-info":[{"award-number":["PCN-2-043\/N\/0\/F, PCN-1-097\/K\/0\/F"]}],"id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1\/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A\/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.<\/jats:p>","DOI":"10.3390\/ijms23020831","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Anticancer Potential of Doxycycline and Minocycline\u2014A Comparative Study on Amelanotic Melanoma Cell Lines"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8260-4339","authenticated-orcid":false,"given":"Jakub","family":"Rok","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7892-0462","authenticated-orcid":false,"given":"Zuzanna","family":"Rzepka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-5325","authenticated-orcid":false,"given":"Justyna","family":"Kowalska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2904-0853","authenticated-orcid":false,"given":"Klaudia","family":"Banach","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-3004","authenticated-orcid":false,"given":"Artur","family":"Beberok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6918-3330","authenticated-orcid":false,"given":"Dorota","family":"Wrze\u015bniok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrc.2016.37","article-title":"From melanocytes to melanomas","volume":"16","author":"Shain","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nature05660","article-title":"Melanocyte biology and skin pigmentation","volume":"445","author":"Lin","year":"2007","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Solano, F. (2020). Photoprotection and skin pigmentation: Melanin-related molecules and some other new agents obtained from natural sources. Molecules, 25.","DOI":"10.3390\/molecules25071537"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/bcpt.12748","article-title":"Pharmacological properties of melanin and its function in health","volume":"120","author":"ElObeid","year":"2017","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Strashilov, S., and Yordanov, A. (2021). Aetiology and pathogenesis of cutaneous melanoma: Current concepts and advances. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126395"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Teixido, C., Castillo, P., Martinez-Vila, C., Arance, A., and Alos, L. (2021). Molecular markers and targets in melanoma. Cells, 10.","DOI":"10.3390\/cells10092320"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1111\/bjd.20427","article-title":"Melanoma pathology: New approaches and classification","volume":"185","author":"Yeh","year":"2021","journal-title":"Br. J. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1111\/1346-8138.15957","article-title":"The genetic and epigenetic basis of distinct melanoma types","volume":"48","author":"Oba","year":"2021","journal-title":"J. Dermatol."},{"key":"ref_9","first-page":"e15087","article-title":"A review of epidemiology and cancer biology of malignant melanoma","volume":"13","author":"Davey","year":"2021","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"460","DOI":"10.3322\/caac.21352","article-title":"State of the science on prevention and screening to reduce melanoma incidence and mortality: The time is now","volume":"66","author":"Tripp","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.hoc.2020.08.011","article-title":"Epidemiology of melanoma","volume":"35","author":"Bolick","year":"2021","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Djavid, A.R., Stonesifer, C., Fullerton, B.T., Wang, S.W., Tartaro, M.A., Kwinta, B.D., Grimes, J.M., Geskin, L.J., and Saenger, Y.M. (2021). Etiologies of melanoma development and prevention measures: A review of the current evidence. Cancers, 13.","DOI":"10.3390\/cancers13194914"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.det.2021.05.015","article-title":"Effect of the COVID-19 pandemic on delayed skin cancer services","volume":"39","author":"Rashid","year":"2021","journal-title":"Dermatol. Clin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s11523-021-00840-3","article-title":"The status of adjuvant and neoadjuvant melanoma therapy, new developments and upcoming challenges","volume":"16","author":"Stege","year":"2021","journal-title":"Target. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.ejso.2021.02.025","article-title":"Surgical excision margins in primary cutaneous melanoma: A systematic review and meta-analysis","volume":"47","author":"Hanna","year":"2021","journal-title":"Eur. J. Surg Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.cps.2021.05.008","article-title":"Radiation therapy for local cutaneous melanoma","volume":"48","author":"Dabestani","year":"2021","journal-title":"Clin. Plast. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1056\/NEJMra2034861","article-title":"Recent advances in the treatment of melanoma","volume":"384","author":"Curti","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Moreira, A., Heinzerling, L., Bhardwaj, N., and Friedlander, P. (2021). Current melanoma treatments: Where do we stand?. Cancers, 13.","DOI":"10.3390\/cancers13020221"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Burzi, L., Alessandrini, A.M., Quaglino, P., Piraccini, B.M., Dika, E., and Ribero, S. (2021). Cutaneous events associated with immunotherapy of melanoma: A review. J. Clin. Med., 10.","DOI":"10.3390\/jcm10143047"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1136\/ejhpharm-2020-002347","article-title":"The incidence and risk of cutaneous toxicities associated with dabrafenib in melanoma patients: A systematic review and meta-analysis","volume":"28","author":"Peng","year":"2021","journal-title":"Eur. J. Hosp. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vukadin, S., Khaznadar, F., Kizivat, T., Vcev, A., and Smolic, M. (2021). Molecular mechanisms of resistance to immune checkpoint inhibitors in melanoma treatment: An update. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070835"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Patel, M., Eckburg, A., Gantiwala, S., Hart, Z., Dein, J., Lam, K., and Puri, N. (2021). Resistance to molecularly targeted therapies in melanoma. Cancers, 13.","DOI":"10.3390\/cancers13051115"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.hoc.2020.08.014","article-title":"Cellular therapy and cytokine treatments for melanoma","volume":"35","author":"Borgers","year":"2021","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s10020-019-0098-x","article-title":"Active repurposing of drug candidates for melanoma based on GWAS, PheWAS and a wide range of omics data","volume":"25","author":"Khosravi","year":"2019","journal-title":"Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1749-6632.2011.06354.x","article-title":"The history of the tetracyclines","volume":"1241","author":"Nelson","year":"2011","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"682682","DOI":"10.3389\/fmicb.2021.682682","article-title":"A complementary mechanism of bacterial mRNA translation inhibition by tetracyclines","volume":"12","author":"Barrenechea","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.clinthera.2005.09.005","article-title":"Safety of doxycycline and minocycline: A systematic review","volume":"27","author":"Smith","year":"2005","journal-title":"Clin. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1128\/MMBR.65.2.232-260.2001","article-title":"Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance","volume":"65","author":"Chopra","year":"2001","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Singh, S., Khanna, D., and Kalra, S. (2021). Minocycline and doxycycline: More than antibiotics. Curr. Mol. Pharmacol., 14.","DOI":"10.2174\/1874467214666210210122628"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s00011-021-01435-4","article-title":"Tetracycline use in treating osteoarthritis: A systematic review","volume":"70","author":"Platt","year":"2021","journal-title":"Inflamm. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1097\/FBP.0000000000000585","article-title":"Tetracyclines, a promise for neuropsychiatric disorders: From adjunctive therapy to the discovery of new targets for rational drug design in psychiatry","volume":"32","author":"Mottin","year":"2021","journal-title":"Behav. Pharmacol."},{"key":"ref_33","first-page":"22","article-title":"Can tetracyclines ensure help in multiple sclerosis immunotherapy?","volume":"7","author":"Thome","year":"2021","journal-title":"J. Clin. Transl. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"642822","DOI":"10.3389\/fphar.2021.642822","article-title":"Pleiotropic effects of tetracyclines in the management of COVID-19: Emerging perspectives","volume":"12","author":"Alqarni","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/bph.12139","article-title":"Minocycline: Far beyond an antibiotic","volume":"169","author":"Zarzuelo","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19336","DOI":"10.18632\/oncotarget.5111","article-title":"Doxycycline: New tricks for an old drug","volume":"6","author":"Barbie","year":"2015","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"605714","DOI":"10.3389\/fonc.2020.605714","article-title":"Repurposing of drug candidates for treatment of skin cancer","volume":"10","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Rok, J., Rzepka, Z., Beberok, A., Pawlik, J., and Wrze\u015bniok, D. (2020). Cellular and molecular aspects of anti-melanoma effect of minocycline\u2014A study of cytotoxicity and apoptosis on human melanotic melanoma cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186917"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104790","DOI":"10.1016\/j.tiv.2020.104790","article-title":"Cytotoxic and proapoptotic effect of doxycycline\u2014An in vitro study on the human skin melanoma cells","volume":"65","author":"Rok","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_40","first-page":"bcr2017222751","article-title":"Amelanotic melanoma: A unique case study and review of the literature","volume":"2018","author":"Herten","year":"2018","journal-title":"BMJ Case Rep."},{"key":"ref_41","first-page":"467","article-title":"Dermatoscopy of amelanotic and hypomelanotic melanoma","volume":"12","author":"Kittler","year":"2014","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1097\/CMR.0000000000000571","article-title":"Amelanotic melanoma","volume":"29","author":"Gong","year":"2019","journal-title":"Melanoma Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chac\u00f3n, M., Pfluger, Y., Angel, M., Waisberg, F., and Enrico, D. (2020). Uncommon subtypes of malignant melanomas: A review based on clinical and molecular perspectives. Cancers, 12.","DOI":"10.3390\/cancers12092362"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1111\/bjd.18722","article-title":"The diagnostic accuracy of dermoscopy and reflectance confocal microscopy for amelanotic\/hypomelanotic melanoma: A systematic review and meta-analysis","volume":"183","author":"Lan","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S0378-5173(01)00988-7","article-title":"Binding of doxycycline to keratin, melanin and human epidermal tissue","volume":"235","author":"Banning","year":"2002","journal-title":"Int. J. Pharm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cbi.2019.02.005","article-title":"Chlortetracycline and melanin biopolymer\u2014The risk of accumulation and implications for phototoxicity: An in vitro study on normal human melanocytes","volume":"303","author":"Rok","year":"2019","journal-title":"Chem. Biol. Interact."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rok, J., Rzepka, Z., Kowalska, J., Banach, K., Beberok, A., and Wrze\u015bniok, D. (2021). Molecular and biochemical basis of minocycline-induced hyperpigmentation-The study on normal human melanocytes exposed to UVA and UVB radiation. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073755"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1111\/php.12497","article-title":"Modulation of melanogenesis and antioxidant status of melanocytes in response to phototoxic action of doxycycline","volume":"91","author":"Rok","year":"2015","journal-title":"Photochem. Photobiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rok, J., Rzepka, Z., Maszczyk, M., Beberok, A., and Wrze\u015bniok, D. (2021). Minocycline impact on redox homeostasis of normal human melanocytes HEMn-LP exposed to UVA radiation and hydrogen peroxide. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041642"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chong Teoh, T., Al-Harbi, S.J., Abdulrahman, A.Y., and Rothan, H.A. (2021). Doxycycline interferes with zika virus serine protease and inhibits virus replication in human skin fibroblasts. Molecules, 26.","DOI":"10.3390\/molecules26144321"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/alr.21660","article-title":"Doxycycline inhibits TGF-\u03b21-induced extracellular matrix production in nasal polyp-derived fibroblasts","volume":"6","author":"Shin","year":"2016","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/j.1600-0765.2005.00843.x","article-title":"Effects of minocycline and doxycycline on cell survival and gene expression in human gingival and periodontal ligament cells","volume":"41","author":"Suzuki","year":"2006","journal-title":"J. Periodontal Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4675","DOI":"10.1167\/iovs.13-11787","article-title":"Doxycycline prevents matrix remodeling and contraction by trichiasis-derived conjunctival fibroblasts","volume":"54","author":"Li","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2015\/787129","article-title":"Cytotoxicity induced by tetracyclines via protein photooxidation","volume":"2015","author":"Fouco","year":"2015","journal-title":"Adv. Toxicol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1093\/jac\/dkl224","article-title":"Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines","volume":"58","author":"Agwuh","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_56","first-page":"1681","article-title":"The pivotal effect of sulindac on melanin-containing cancers","volume":"74","author":"Delijewski","year":"2017","journal-title":"Acta Pol. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1111\/fcp.12503","article-title":"MIM1 induces COLO829 melanoma cell death through mitochondrial membrane breakdown, GSH depletion, and DNA damage","volume":"34","author":"Respondek","year":"2020","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1007\/s12253-019-00715-z","article-title":"Mcl-1 inhibitor induces cells death in BRAF-mutant amelanotic melanoma trough GSH depletion, DNA damage and cell cycle changes","volume":"26","author":"Respondek","year":"2020","journal-title":"Pathol. Oncol. Res."},{"key":"ref_59","first-page":"7993","article-title":"Combined pitavastatin and dacarbazine treatment activates apoptosis and autophagy resulting in synergistic cytotoxicity in melanoma cells","volume":"14","author":"Aliwaini","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Charignon, E., Bouch\u00e9, M., Clave-Darcissac, C., Dahm, G., Ichim, G., Clotagatide, A., Mertani, H.C., Telouk, P., Caramel, J., and Diaz, J.J. (2020). In cellulo evaluation of the therapeutic potential of NHC platinum compounds in metastatic cutaneous melanoma. Int. J. Mol. Sci, 21.","DOI":"10.3390\/ijms21217826"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ejphar.2011.08.003","article-title":"Interaction between ciprofloxacin and melanin: The effect on proliferation and melanization in melanocytes","volume":"669","author":"Beberok","year":"2011","journal-title":"Eur. J. Pharmacol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.pharep.2017.07.007","article-title":"Ciprofloxacin-mediated induction of S-phase cell cycle arrest and apoptosis in COLO829 melanoma cells","volume":"70","author":"Beberok","year":"2018","journal-title":"Pharmacol. Rep."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"104884","DOI":"10.1016\/j.tiv.2020.104884","article-title":"The role of MITF and Mcl-1 proteins in the antiproliferative and proapoptotic effect of ciprofloxacin in amelanotic melanoma cells: In silico and in vitro study","volume":"66","author":"Beberok","year":"2020","journal-title":"Toxicol. In Vitro"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.tiv.2018.12.002","article-title":"Moxifloxacin as an inducer of apoptosis in melanoma cells: A study at the cellular and molecular level","volume":"55","author":"Beberok","year":"2019","journal-title":"Toxicol. In Vitro"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.apsb.2018.01.008","article-title":"Targeting ERK, an Achilles\u2019 Heel of the MAPK pathway, in cancer therapy","volume":"8","author":"Liu","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1124\/jpet.103.055806","article-title":"Repression of mitogen-activated protein kinase (MAPK) phosphatase-1 by anthracyclines contributes to their antiapoptotic activation of p44\/42-MAPK","volume":"307","author":"Small","year":"2003","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1038\/sj.jid.5700870","article-title":"ERK1\/2 is highly phosphorylated in melanoma metastases and protects melanoma cells from cisplatin-mediated apoptosis","volume":"127","author":"Mirmohammadsadegh","year":"2007","journal-title":"J. Investig. Dermatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"152877","DOI":"10.1016\/j.phymed.2019.152877","article-title":"p44\/42 MAPK signaling is a prime target activated by phenylethyl resorcinol in its anti-melanogenic action","volume":"58","author":"Kang","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Lee, S., Rauch, J., and Kolch, W. (2020). Targeting MAPK signaling in cancer: Mechanisms of drug resistance and sensitivity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21031102"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1038\/sj.leu.2401222","article-title":"The roles of signaling by the p42\/p44 mitogen-activated protein (MAP) kinase pathway; a potential route to radio- and chemo-sensitization of tumor cells resulting in the induction of apoptosis and loss of clonogenicity","volume":"12","author":"Dent","year":"1998","journal-title":"Leukemia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"102995","DOI":"10.1016\/j.critrevonc.2020.102995","article-title":"Metabolic rewiring in melanoma drug-resistant cells","volume":"153","author":"Bristot","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1016\/j.bbrc.2020.01.051","article-title":"Dasatinib, a second-generation tyrosine kinase inhibitor, induces melanogenesis via ERK-CREB-MITF-tyrosinase signaling in normal human melanocytes","volume":"523","author":"Kang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1007\/s00018-014-1791-0","article-title":"MITF in melanoma: Mechanisms behind its expression and activity","volume":"72","author":"Hartman","year":"2015","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1038\/jid.2014.319","article-title":"Pro-survival role of MITF in melanoma","volume":"135","author":"Hartman","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Czarnecka, A.M., Bartnik, E., Fiedorowicz, M., and Rutkowski, P. (2020). Targeted therapy in melanoma and mechanisms of resistance. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134576"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41598-018-37522-6","article-title":"MITF has a central role in regulating starvation-induced autophagy in melanoma","volume":"9","author":"Sigurbjornsdottir","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s12943-020-01290-7","article-title":"The complex relationship between MITF and the immune system: A melanoma immunotherapy (response) factor?","volume":"19","author":"Ballotti","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/labinvest.2017.9","article-title":"The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology","volume":"97","author":"Kawakami","year":"2017","journal-title":"Lab. Investig."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4117","DOI":"10.12659\/MSM.903245","article-title":"Induction of mitochondrial dysfunction and oxidative damage by antibiotic drug doxycycline enhances the responsiveness of glioblastoma to chemotherapy","volume":"23","author":"Tan","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1002\/jps.20874","article-title":"Oxidative stress and apoptosis: Impact on cancer therapy","volume":"96","author":"Ozben","year":"2007","journal-title":"J. Pharm. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Kennedy, L., Sandhu, J.K., Harper, M.E., and Cuperlovic-Culf, M. (2020). Role of glutathione in cancer: From mechanisms to therapies. Biomolecules, 10.","DOI":"10.3390\/biom10101429"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.3390\/cancers3011285","article-title":"Glutathione in cancer cell death","volume":"3","author":"Ortega","year":"2011","journal-title":"Cancers"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/cdd.2009.107","article-title":"Apoptosis and glutathione: Beyond an antioxidant","volume":"16","author":"Franco","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"205","DOI":"10.15171\/apb.2019.024","article-title":"Understanding apoptosis and apoptotic pathways targeted cancer therapeutics","volume":"9","author":"Jan","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.molcel.2020.05.014","article-title":"Cell death in the origin and treatment of cancer","volume":"78","author":"Strasser","year":"2020","journal-title":"Mol. Cell."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41571-020-0341-y","article-title":"Targeting apoptosis in cancer therapy","volume":"17","author":"Carneiro","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e985913","DOI":"10.4161\/23723556.2014.985913","article-title":"Autophagy, cell death, and cancer","volume":"2","author":"Lin","year":"2015","journal-title":"Mol. Cell. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Linder, B., and K\u00f6gel, D. (2019). Autophagy in cancer cell death. Biology, 8.","DOI":"10.3390\/biology8040082"},{"key":"ref_89","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_90","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1080\/15548627.2019.1695398","article-title":"CASP9 (caspase 9) is essential for autophagosome maturation through regulation of mitochondrial homeostasis","volume":"16","author":"An","year":"2020","journal-title":"Autophagy"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6485","DOI":"10.1074\/jbc.M113.536854","article-title":"A Complex between Atg7 and Caspase-9: A novel mechanism of cross-regulation between autophagy and apoptosis","volume":"289","author":"Han","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Choi, C.Y., Vo, M.T., Nicholas, J., and Choi, Y.B. (2021). Autophagy-competent mitochondrial translation elongation factor TUFM inhibits caspase-8-mediated apoptosis. Cell Death Differ.","DOI":"10.1038\/s41418-021-00868-y"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5459209","DOI":"10.1155\/2020\/5459209","article-title":"Minocycline induces autophagy and inhibits cell proliferation in LPS-stimulated THP-1 cells","volume":"2020","author":"Sun","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"166","DOI":"10.4161\/auto.7.2.14043","article-title":"Minocycline inhibits the growth of glioma by inducing autophagy","volume":"7","author":"Liu","year":"2011","journal-title":"Autophagy"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"173","DOI":"10.3892\/br.2015.554","article-title":"Minocycline induces protective autophagy in vascular endothelial cells exposed to an in vitro model of ischemia\/reperfusion-induced injury","volume":"4","author":"Dong","year":"2016","journal-title":"Biomed. Rep."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10495-019-01521-3","article-title":"Minocycline promotes cardiomyocyte mitochondrial autophagy and cardiomyocyte autophagy to prevent sepsis-induced cardiac dysfunction by Akt\/mTOR signaling","volume":"24","author":"Zhang","year":"2019","journal-title":"Apoptosis"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijcard.2020.07.016","article-title":"Doxycycline decreases amyloidogenic light chain-induced autophagy in isolated primary cardiac myocytes","volume":"321","author":"Wilson","year":"2020","journal-title":"Int. J. Cardiol."},{"key":"ref_98","first-page":"63","article-title":"Tetracycline derivative minocycline inhibits autophagy and inflammation in concanavalin-a-activated human hepatoma cells","volume":"8","author":"Desjarlais","year":"2014","journal-title":"Gene Regul. Syst. Bio."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1080\/15384101.2016.1241929","article-title":"Doxycycline inhibits the cancer stem cell phenotype and epithelial-to-mesenchymal transition in breast cancer","volume":"16","author":"Zhang","year":"2017","journal-title":"Cell Cycle"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/831\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:14:54Z","timestamp":1760364894000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":99,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23020831"],"URL":"https:\/\/doi.org\/10.3390\/ijms23020831","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}