{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:41:26Z","timestamp":1790502086551,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Principal component analysis (PCA) multivariate analysis was applied to study the cytotoxic activity of essential oils from various species of the Pistacia genus on human tumor cell lines. In particular, the cytotoxic activity of essential oils obtained from P. lentiscus, P. lentiscus var. chia (mastic gum), P. terebinthus, P. vera, and P. integerrima, was screened on three human adenocarcinoma cell lines: MCF-7 (breast), 2008 (ovarian), and LoVo (colon). The results indicate that all the Pistacia phytocomplexes, with the exception of mastic gum oil, induce cytotoxic effects on one or more of the three cell lines. PCA highlighted the presence of different cooperating clusters of bioactive molecules. Cluster variability among species, and even within the same species, could explain some of the differences seen among samples suggesting the presence of both common and species-specific mechanisms. Single molecules from one of the most significant clusters were tested, but only bornyl-acetate presented cytotoxic activity, although at much higher concentrations (IC50 = 138.5 \u00b5g\/mL) than those present in the essential oils, indicating that understanding of the full biological effect requires a holistic vision of the phytocomplexes with all its constituents.<\/jats:p>","DOI":"10.3390\/molecules22081336","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T10:07:40Z","timestamp":1502446060000},"page":"1336","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Human Adenocarcinoma Cell Line Sensitivity to Essential Oil Phytocomplexes from Pistacia Species: a Multivariate Approach"],"prefix":"10.3390","volume":"22","author":[{"given":"Alessandro","family":"Buriani","sequence":"first","affiliation":[{"name":"Maria Paola Belloni Center for Personalized Medicine, Data Medica Group (Synlab Limited), 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6111-332X","authenticated-orcid":false,"given":"Stefano","family":"Fortinguerra","sequence":"additional","affiliation":[{"name":"Maria Paola Belloni Center for Personalized Medicine, Data Medica Group (Synlab Limited), 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Sorrenti","sequence":"additional","affiliation":[{"name":"Maria Paola Belloni Center for Personalized Medicine, Data Medica Group (Synlab Limited), 35100 Padova, Italy"},{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35100 Padova, Italy"},{"name":"Department of Biomedical Sciences, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-6953","authenticated-orcid":false,"given":"Stefano","family":"Dall\u2019Acqua","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabbriella","family":"Innocenti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Montopoli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-8227","authenticated-orcid":false,"given":"Daniela","family":"Gabbia","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carrara","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35100 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Pelkonen, O., Duez, P., Vuorela, P.M., and Vuorela, H. (2017). Systems Network Pharmaco-Toxicology in the Study of Herbal Medicines. Toxicology of Herbal Products, Springer.","DOI":"10.1007\/978-3-319-43806-1"},{"key":"ref_2","first-page":"007","article-title":"The systems biology oriented, holistic vision of personalized medicine and the emerging concept of proactive herbal medicine","volume":"1","author":"Buriani","year":"2015","journal-title":"Jacobs J. Intern Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jep.2012.01.055","article-title":"Omic techniques in systems biology approaches to traditional Chinese medicine research: present and future","volume":"140","author":"Buriani","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.21101\/cejph.a3886","article-title":"Naturally occurring substances and their role in chemo-protective effects","volume":"21","author":"Urban","year":"2013","journal-title":"Cent. Eur. J. Public Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"775S","DOI":"10.1093\/jn\/129.3.775S","article-title":"Prevention and therapy of cancer by dietary monoterpenes","volume":"129","author":"Crowell","year":"1999","journal-title":"J. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00280-003-0684-y","article-title":"Phase I trial of perillyl alcohol administered four times daily continuously","volume":"52","author":"Dubey","year":"2003","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e219815","DOI":"10.1155\/2013\/219815","article-title":"Five Pistacia. species (P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus): A review of their traditional uses, phytochemistry, and pharmacology","volume":"15","author":"Bozorgi","year":"2013","journal-title":"Sci. World J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/ptr.5165","article-title":"Anticancer activities of essential oils constituents and synergy with conventional therapies: A review","volume":"28","author":"Lesgards","year":"2014","journal-title":"Phytother. Res."},{"key":"ref_9","first-page":"591","article-title":"Anticancer activity of essential oils and their chemical components\u2014A review","volume":"4","author":"Bayala","year":"2014","journal-title":"Am. J. Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000224548","article-title":"Inhibition of murine subcutaneous and intravenous benzo (rst) pentaphene. Carcinogenesis by sweet orange oils and d-limonene","volume":"25","author":"Homburger","year":"1971","journal-title":"Oncology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/carcin\/12.1.115","article-title":"Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone carcinogenesis in mice by D-limonene and citrus fruit oils","volume":"12","author":"Wattenberg","year":"1991","journal-title":"Carcinogenesis"},{"key":"ref_12","first-page":"4021","article-title":"Limonene-induced regression of mammary carcinomas","volume":"15","author":"Haag","year":"1992","journal-title":"Cancer Res."},{"key":"ref_13","first-page":"3540","article-title":"Limonene chemoprevention of mammary carcinoma induction following direct in situ transfer of v-Ha-ras","volume":"54","author":"Gould","year":"1994","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.3748\/wjg.v10.i14.2140","article-title":"Inhibition of growth and metastasis of human gastric cancer implanted in nude mice by d-limonene","volume":"10","author":"Lu","year":"2004","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e953451","DOI":"10.1155\/2014\/953451","article-title":"Antitumor activity of monoterpenes found in essential oils","volume":"2014","author":"Sobral","year":"2014","journal-title":"Sci. World J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.canlet.2004.06.019","article-title":"Geraniol, a component of plant essential oils, modulates DNA synthesis and potentiates 5-fluorouracil efficacy on human colon tumor xenografts","volume":"215","author":"Carnesecchi","year":"2004","journal-title":"Cancer Lett."},{"key":"ref_17","first-page":"989","article-title":"Antiproliferative activity of essential oils derived from plants belonging to the Magnoliophyta division","volume":"29","author":"Lampronti","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1211\/jpp.59.12.0005","article-title":"Potentiating effect of beta-caryophyllene on anticancer activity of alpha-humulene, isocaryophyllene and paclitaxel","volume":"59","author":"Legault","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jdermsci.2010.04.013","article-title":"Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: Downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway","volume":"59","author":"Pal","year":"2010","journal-title":"J. Dermatol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jnutbio.2009.12.007","article-title":"Chemopreventive effects of \u03b2-ionone and geraniol during rat hepatocarcinogenesis promotion: Distinct actions on cell proliferation, apoptosis, HMGCoA reductase, and RhoA","volume":"22","author":"Cardozo","year":"2011","journal-title":"J. Nutr. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1021\/jf204525b","article-title":"Effects of thymol on B16-F10 melanoma cells","volume":"60","author":"Satooka","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4236\/ajps.2012.31002","article-title":"Taxonomic Revision of the Genus Pistacia L. (Anacardiaceae)","volume":"3","author":"Porter","year":"2012","journal-title":"AJPS"},{"key":"ref_23","unstructured":"Zohara, Y., and Nativ, D. (2014). Medicinal and Aromatic Plants of the Middle-East, Springer."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1207\/s15327914nc5501_11","article-title":"Mastic oil from Pistacia lentiscus var. chia inhibits growth and survival of human K562 leukemia cells and attenuates angiogenesis","volume":"55","author":"Loutrari","year":"2006","journal-title":"Nutr. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.phymed.2006.03.009","article-title":"Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia","volume":"14","author":"Balan","year":"2007","journal-title":"Phytomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"789","DOI":"10.3390\/cancers3010789","article-title":"Mastic oil inhibits the metastatic phenotype of mouse lung adenocarcinoma cells","volume":"3","author":"Loutrari","year":"2011","journal-title":"Cancers"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1080\/01635581.2011.607546","article-title":"Current evidence on the anticancer potential of Chios mastic gum","volume":"63","author":"Giaginis","year":"2011","journal-title":"Nutr. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1021\/np200161a","article-title":"(8R)-3\u03b2,8-Dihydroxypolypoda-13E,17E,21-triene induces cell cycle arrest and apoptosis in treatment-resistant prostate cancer cells","volume":"74","author":"Morad","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_29","first-page":"63","article-title":"A mastic gum extract induces suppression of growth of human colorectal tumor xenografts in immunodeficient mice","volume":"23","author":"Dimas","year":"2009","journal-title":"In Vivo"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Catalani, S., Palma, F., Battistelli, S., and Benedetti, S. (2017). Oxidative stress and apoptosis induction in human thyroid carcinoma cells exposed to the essential oil from Pistacia lentiscus aerial parts. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172138"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3782","DOI":"10.1038\/s41598-017-03971-8","article-title":"Dietary mastic oil extracted from Pistacia lentiscus var. chia suppresses tumor growth in experimental colon cancer models","volume":"7","author":"Spyridopoulou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s11418-011-0589-8","article-title":"In vitro cytotoxic screening of selected Saudi medicinal plants","volume":"66","author":"Almehdar","year":"2012","journal-title":"J. Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"375","DOI":"10.4103\/0250-474X.107085","article-title":"The study of anticancer and antifungal activities of Pistacia integerrima extract in vitro","volume":"74","author":"Bibi","year":"2012","journal-title":"Indian J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/j.fct.2011.11.012","article-title":"Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells","volume":"50","author":"Rezaei","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_35","first-page":"128","article-title":"Induction of apoptosis by pistachio (Pistacia vera L.) hull extract and its molecular mechanisms of action in human hepatoma cell line HepG2","volume":"61","author":"Fathalizadeh","year":"2015","journal-title":"Cell. Mol. Biol."},{"key":"ref_36","first-page":"233","article-title":"Cytotoxicity and antiangiogenic effects of Rhus coriaria, Pistacia vera and Pistacia khinjuk oleoresin methanol extracts","volume":"10","author":"Mirian","year":"2015","journal-title":"Res. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3109\/13880209.2015.1079222","article-title":"Evaluation of Pistacia lentiscus seed oil and phenolic compounds for in vitro antiproliferative effects against BHK21 cells","volume":"54","author":"Mezni","year":"2016","journal-title":"Pharm. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.fct.2016.06.028","article-title":"An apolar Pistacia lentiscus L. leaf extract: GC-MS metabolic profiling and evaluation of cytotoxicity and apoptosis inducing effects on SH-SY5Y and SK-N-BE(2)C cell lines","volume":"95","author":"Piccolella","year":"2016","journal-title":"Food Chem. Toxicol."},{"key":"ref_39","first-page":"3293","article-title":"Cytotoxic activity of essential oils from labiatae and lauraceae families against in vitro human tumor models","volume":"27","author":"Loizzo","year":"2007","journal-title":"Anticancer Res."},{"key":"ref_40","first-page":"1481","article-title":"Chemical Diversity, Biological Activity, and GeneticAspects of Three Ocotea Species from the Amazon","volume":"8","author":"Moreira","year":"2013","journal-title":"Nat. Prod. Commun."},{"key":"ref_41","first-page":"1081","article-title":"Juglans regia and J. nigra, two trees important in traditional medicine: A comparison of leaf essential oil compositions and biological activities","volume":"18","author":"Paudel","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1021\/np50083a016","article-title":"Plant anticancer agents, L. cytotoxic triterpenes from Sandoricum koetjape stems","volume":"55","author":"Kaneda","year":"1992","journal-title":"J. Nat. Prod."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2707","DOI":"10.3390\/nu7042707","article-title":"Cytotoxic activity of Piper cubeba extract in breast cancer cell lines","volume":"10","author":"Graidist","year":"2015","journal-title":"Nutrients"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"397821","DOI":"10.1155\/2015\/397821","article-title":"Exploitation of cytotoxicity of some essential oils for translation in cancer therapy","volume":"2015","author":"Russo","year":"2015","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_45","first-page":"1","article-title":"The cytotoxic activity of annona muricata leaf oil from badagary, Nigeria","volume":"1","author":"Owolabi","year":"2013","journal-title":"Am. J. Essent. Oil Nat. Prod."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shapira, S., Pleban, S., Kazanov, D., Tirosh, P., and Arber, N. (2016). Terpinen-4-ol: A novel and promising therapeutic agent for human gastrointestinal cancers. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156540"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/ffj.2730060406","article-title":"Chemical composition of the essential oils from the gum and from various parts of Pistacia lentiscus L. (mastic gum tree)","volume":"6","author":"Boelens","year":"1991","journal-title":"Flavour Fragr. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/ffj.2730060313","article-title":"Essential oils from the leaves of three Pistacia species grown in Egypt","volume":"6","author":"Schamp","year":"1991","journal-title":"Flavour Fragr. J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1055\/s-2006-960856","article-title":"Chemical composition and antimicrobial activity of the essential oils of Pistacia lentiscus var. chia","volume":"65","author":"Magiatis","year":"1999","journal-title":"Planta Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1016\/0031-9422(81)80135-5","article-title":"Trace constituents in the essential oil of Thymus capitatus","volume":"20","author":"Papageorgiou","year":"1981","journal-title":"Phytochemistry"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.foodchem.2007.09.036","article-title":"Essential oil composition of Pistacia lentiscus L. and Myrtus communis L.: Evaluation of antioxidant capacity of methanolic extracts","volume":"107","author":"Gardeli","year":"2008","journal-title":"Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/8\/1336\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:42:11Z","timestamp":1760208131000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/8\/1336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":51,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2017,8]]}},"alternative-id":["molecules22081336"],"URL":"https:\/\/doi.org\/10.3390\/molecules22081336","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]}}}