{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:49:19Z","timestamp":1782402559705,"version":"3.54.5"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005322","name":"Recep Tayyip Erdogan University, Scientific Research Projects","doi-asserted-by":"publisher","award":["TSA-2020-1073"],"award-info":[{"award-number":["TSA-2020-1073"]}],"id":[{"id":"10.13039\/501100005322","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Recep Tayyip Erdo\u011fan University Development Foundation","award":["02025010028752"],"award-info":[{"award-number":["02025010028752"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives:\u00a0Lavandula stoechas has reported bioactivities, but its selective anticancer potential in human models remains insufficiently defined. This study aimed to compare cytotoxicity and selectivity of ethanol and methanol extracts prepared from fresh and dried L. stoechas and to profile candidate bioactive metabolites. Methods: Aerial parts Lavandula stoechas L. subsp. stoechas (L. stoechas L.) were extracted with ethanol or methanol from fresh (LsFE, LsFM) and dried (LsDE, LsDM) material. Cytotoxicity was assessed in cancer (MDA-MB-231, T98G, RT4) and non-malignant (hGF, ARPE-19) cells using Hoechst 33342-stained nuclear counts and MTS viability at 24\u201348 h. Metabolite identification was performed using LC\u2013QTOF\u2013MS in both positive and negative ESI modes, supported by database search results. Results: All extracts reduced viability in a dose- and time-dependent manner. Among them, the ethanol extract from fresh material (LsFE) displayed the highest cytotoxic potency and the most favorable selectivity profile, markedly reducing viability in breast (MDA-MB-231) and glioblastoma (T98G) cells while exerting only mild effects on non-malignant fibroblast (hGF) and retinal epithelial (ARPE-19) cells. In contrast, extracts from dried material, particularly LsDE, showed broader cytotoxicity across both cancerous and non-cancerous lines. LC\u2013MS highlighted sesquiterpenoids (Kikkanol A; 3(4\u21925)-Abeo-4,11:4,12-diepoxy-3-eudesmanol), phenolics (tyrosol; 3,4-dihydroxybenzoic acid), flavonoid\/ionone derivatives (luteolin 5,3\u2032-dimethyl ether; 3-hydroxy-\u03b2-ionone), oxidized fatty acids (9(S)-HpODE, \u03b1-EpODE, 5,12-dihydroxy-eicosatetraenoic acid), and jasmonates (12-hydroxyjasmonic acid; dihydrojasmonic acid methyl ester), especially enriched in LsFE. Conclusions: Ethanol extracts of L. stoechas L., especially LsFE, demonstrated selective cytotoxicity against cancer cells while exerting relatively mild effects on non-malignant cells. The metabolite profile of L. stoechas L. extracts revealed a diverse composition, including phenolics, terpenoids, flavonoids, and oxidized lipids, which are commonly associated with biological activity. These results suggest that LsFE is a promising candidate for further studies focusing on compound isolation and mechanistic analysis.<\/jats:p>","DOI":"10.3390\/ph18111706","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T15:07:31Z","timestamp":1762787251000},"page":"1706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Anticancer Effects and Phytochemical Profile of Lavandula stoechas"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1115-2005","authenticated-orcid":false,"given":"Hatice","family":"Sevim Nalkiran","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53020, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7246-2592","authenticated-orcid":false,"given":"Ihsan","family":"Nalkiran","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53020, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Cao, B., Bray, F., Beltr\u00e1n-S\u00e1nchez, H., Ginsburg, O., Soneji, S., and Soerjomataram, I. (2017). Benchmarking life expectancy and cancer mortality: Global comparison with cardiovascular disease 1981\u20132010. BMJ, 357.","DOI":"10.1136\/bmj.j2765"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Seca, A.M.L., and Pinto, D. (2018). Plant Secondary Metabolites as Anticancer Agents: Successes in Clinical Trials and Therapeutic Application. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19010263"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"96","DOI":"10.2174\/1568026616666160530154407","article-title":"Natural Plant Extracts as Potential Therapeutic Agents for the Treatment of Cancer","volume":"17","author":"Goyal","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Pavan, A.R., Silva, G.D., Jornada, D.H., Chiba, D.E., Fernandes, G.F., Man Chin, C., and Dos Santos, J.L. (2016). Unraveling the Anticancer Effect of Curcumin and Resveratrol. Nutrients, 8.","DOI":"10.3390\/nu8110628"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.biopha.2017.01.161","article-title":"Green tea and its anti-angiogenesis effects","volume":"89","author":"Rashidi","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.indcrop.2015.03.088","article-title":"Lavandula stoechas essential oil from Spain: Aromatic profile determined by gas chromatography\u2013mass spectrometry, antioxidant and lipoxygenase inhibitory bioactivities","volume":"73","author":"Carrasco","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0378-8741(99)00198-1","article-title":"Ethnopharmacological evaluation of the anticonvulsant, sedative and antispasmodic activities of Lavandula stoechas L.","volume":"71","author":"Gilani","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jep.2016.05.063","article-title":"Anti-inflammatory activity of hydroalcoholic extracts of Lavandula dentata L. and Lavandula stoechas L.","volume":"190","author":"Algieri","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4364","DOI":"10.1021\/jf0603329","article-title":"Chemical composition, seasonal variability, and antifungal activity of Lavandula stoechas L. ssp. stoechas essential oils from stem\/leaves and flowers","volume":"54","author":"Angioni","year":"2006","journal-title":"J. Agric. Food Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mushtaq, A., Anwar, R., Gohar, U.F., Ahmad, M., Marc, R.A., Mure\u015fan, C.C., Irimie, M., and Bobescu, E. (2021). Biomolecular Evaluation of Lavandula stoechas L. for Nootropic Activity. Plants, 10.","DOI":"10.3390\/plants10061259"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1080\/13880209.2016.1230636","article-title":"Antibacterial, antioxidant and anti-proliferative properties and zinc content of five south Portugal herbs","volume":"55","author":"Nunes","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1515\/znc-2002-9-1007","article-title":"The chemical constituents and biological activity of essential oil of Lavandula stoechas ssp. stoechas","volume":"57","author":"Goren","year":"2002","journal-title":"Z. Naturforsch. C J. Biosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ahamad, R., Kumar, S., Akhtar, M., Aqil, M., Yar, M.S., Akram, M., Ismail, M.V., and Mujeeb, M. (2025). A Comprehensive Review of Lavandula stoechas L. (Ustukhuddus) Plant: Phytochemistry, Pharmacology, and In Silico Studies. Chem. Biodivers., 22.","DOI":"10.1002\/cbdv.202401996"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Boukhatem, M.N., Sudha, T., Darwish, N.H.E., Chader, H., Belkadi, A., Rajabi, M., Houche, A., Benkebailli, F., Oudjida, F., and Mousa, S.A. (2020). A New Eucalyptol-Rich Lavender (Lavandula stoechas L.) Essential Oil: Emerging Potential for Therapy against Inflammation and Cancer. Molecules, 25.","DOI":"10.3390\/molecules25163671"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ndhlala, A.R., I\u015f\u0131k, M., Kavaz Y\u00fcksel, A., and Dikici, E. (2024). Phenolic Content Analysis of Two Species Belonging to the Lamiaceae Family: Antioxidant, Anticholinergic, and Antibacterial Activities. Molecules, 29.","DOI":"10.3390\/molecules29020480"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Benali, T., Lemhadri, A., Harboul, K., Chtibi, H., Khabbach, A., Jadouali, S.M., Quesada-Romero, L., Louahlia, S., Hammani, K., and Ghaleb, A. (2023). Chemical Profiling and Biological Properties of Essential Oils of Lavandula stoechas L. Collected from Three Moroccan Sites: In Vitro and In Silico Investigations. Plants, 12.","DOI":"10.3390\/plants12061413"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lee, J.-E., Jayakody, J.T.M., Kim, J.-I., Jeong, J.-W., Choi, K.-M., Kim, T.-S., Seo, C., Azimi, I., Hyun, J., and Ryu, B. (2024). The Influence of Solvent Choice on the Extraction of Bioactive Compounds from Asteraceae: A Comparative Review. Foods, 13.","DOI":"10.3390\/foods13193151"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131918","DOI":"10.1016\/j.foodchem.2021.131918","article-title":"Influence of the extraction method on the recovery of bioactive phenolic compounds from food industry by-products","volume":"378","author":"Romero","year":"2022","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Domingues, J., Delgado, F., Gon\u00e7alves, J.C., Zuzarte, M., and Duarte, A.P. (2023). Mediterranean Lavenders from Section Stoechas: An Undervalued Source of Secondary Metabolites with Pharmacological Potential. Metabolites, 13.","DOI":"10.3390\/metabo13030337"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Syaj, H., Aboalhaija, N., Afifi, F., Abu-Dahab, R., Abusulieh, S., and Amro, R. (2025). Phytochemistry and Antiproliferative Potential of a Naturalized Plant in Jordan: Lavandula stoechas. Chem. Biodivers., 22.","DOI":"10.1002\/cbdv.202500181"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.2174\/1573407215666190916102325","article-title":"Evaluation of Cytotoxic Activity of Lavandula stoechas Aerial Parts Fractions against HepG2 Cell Lines","volume":"16","author":"Siddiqui","year":"2020","journal-title":"Curr. Bioact. Compd."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Cadena-I\u00f1iguez, J., Santiago-Osorio, E., S\u00e1nchez-Flores, N., Salazar-Aguilar, S., Soto-Hern\u00e1ndez, R.M., Riviello-Flores, M.L., Mac\u00edas-Zaragoza, V.M., and Agui\u00f1iga-S\u00e1nchez, I. (2024). The Cancer-Protective Potential of Protocatechuic Acid: A Narrative Review. Molecules, 29.","DOI":"10.3390\/molecules29071439"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s43094-024-00700-7","article-title":"Hydroxytyrosol in cancer research: Recent and historical insights on discoveries and mechanisms of action","volume":"10","author":"Kumar","year":"2024","journal-title":"Futur. J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1080\/01635581.2017.1339818","article-title":"Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells","volume":"69","author":"Zubair","year":"2017","journal-title":"Nutr. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102454","DOI":"10.1016\/j.jksus.2022.102454","article-title":"Isolation of oleanolic acid from Lavandula stoechas and its potent anticancer properties against MCF-7 cancer cells via induced apoptosis","volume":"35","author":"Farooq","year":"2023","journal-title":"J. King Saud Univ. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jarocka-Karpowicz, I., and Markowska, A. (2021). Therapeutic Potential of Jasmonic Acid and Its Derivatives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22168437"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3892\/mmr.2016.6061","article-title":"Methyl jasmonate induces the apoptosis of human colorectal cancer cells via downregulation of EZH2 expression by microRNA-101","volume":"15","author":"Peng","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_28","unstructured":"Mill, R.R. (1982). Flora of Turkey and the East Aegean Islands, Edinburgh University Press. [1st ed.]."},{"key":"ref_29","first-page":"9","article-title":"Morphological, Anatomical and Phytochemical Characterizations of Lavandula stoechas L. subsp. stoechas Growing in Turkey","volume":"6","author":"Demirci","year":"2019","journal-title":"Nat. Volatiles Essent. Oils"},{"key":"ref_30","unstructured":"Nyffeler, R.G.A. (2021, November 12). Occurrence Dataset. Available online: https:\/\/www.gbif.org\/occurrence\/3383283857."},{"key":"ref_31","unstructured":"Nalkiran, H.S. (2025, October 17). Digital Voucher Specimen of Lavandula stoechas L. subsp. Stoechas Collected from T\u00fcrkiye. Available online: https:\/\/doi.org\/10.5281\/zenodo.17374963."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Nalkiran, I., and Sevim Nalkiran, H. (2025). Phytochemical Profile and Anticancer Potential of Helichrysum arenarium Extracts on Glioblastoma, Bladder Cancer, and Breast Cancer Cells. Pharmaceuticals, 18.","DOI":"10.3390\/ph18020144"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sevim Nalkiran, H., Akcora Yildiz, D., Saydam, F., Guzel, A.I., and Nalkiran, I. (2023). Targeting the anaphase-promoting complex\/cyclosome (APC\/C) enhanced antiproliferative and apoptotic response in bladder cancer. Saudi J. Biol. Sci., 30.","DOI":"10.1016\/j.sjbs.2023.103564"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1706\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:52:17Z","timestamp":1762865537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1706"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":33,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111706"],"URL":"https:\/\/doi.org\/10.3390\/ph18111706","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]}}}