{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:13:52Z","timestamp":1788567232269,"version":"build-2803163510"},"reference-count":66,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background:Becium grandiflorum is a fragrant perennial shrub of the Lamiaceae family. Objectives: The current study aimed to explore the cytotoxic potential of the n-hexane fraction from Becium grandiflorum aerial parts and, further, isolate its major diterpene and conduct in vitro and in vivo anticancer activities along with its molecular mechanism and synergy with doxorubicin. Methods: The hydroalcoholic extract of Becium grandiflorum aerial parts was fractionated, and the n-hexane fraction was analyzed via GC-MS. The major isolated diterpene, 18-epoxy-pimara-8(14),15-diene (epoxy-pimaradiene), was quantified using UPLC-PDA. Cytotoxicity assays were conducted on HCT-116, MCF-7, MDA-MB-231, and HepG2 cell lines. The synergistic effect with doxorubicin was tested on HepG2 cells. In vivo anticancer activity was evaluated using the Ehrlich ascites carcinoma model, and molecular docking analyzed Bax-Bcl2 interactions. Results: The n-hexane fraction contained 21 compounds, mainly oxygenated diterpenes, and the major isolated compound was epoxy-pimaradiene, with a quantity of 0.3027 mg\/mg. N-Hexane fraction and epoxy-pimaradiene exhibited strong cytotoxicity against HepG2 cells, induced apoptosis, and G2\/M arrest. The combination of epoxy-pimaradiene with doxorubicin lowered the IC50 of doxorubicin from 4 \u00b5M to 1.78 \u00b5M. In vivo, both reduced tumor growth and increased necrotic tumor areas. Molecular docking revealed disruption of Bax-Bcl2. Conclusions: The findings suggest that B. grandiflorum and its major diterpene, epoxy-pimaradiene, exhibit potent anticancer activity, particularly against liver cancer cells. Epoxy-pimaradiene enhances doxorubicin\u2019s efficacy, induces apoptosis, and inhibits tumor progression. Further studies are needed to explore their therapeutic potential.<\/jats:p>","DOI":"10.3390\/nu17071164","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T12:41:02Z","timestamp":1743079262000},"page":"1164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Phytochemical Analysis and In Vivo Anticancer Effect of Becium grandiflorum: Isolation and Characterization of a Promising Cytotoxic Diterpene"],"prefix":"10.3390","volume":"17","author":[{"given":"Christeen","family":"Fahim","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City 11837, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maha R. A.","family":"Abdollah","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City 11837, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7531-4552","authenticated-orcid":false,"given":"Rola M.","family":"Labib","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6526-298X","authenticated-orcid":false,"given":"Nehal","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-2265","authenticated-orcid":false,"given":"Noha","family":"Swilam","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, The British University in Egypt (BUE), El-Sherouk City 11837, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7801543","DOI":"10.1155\/2018\/7801543","article-title":"Medicinal plants of the family Lamiaceae in pain therapy: A review","volume":"2018","author":"Uritu","year":"2018","journal-title":"Pain Res. Manag."},{"key":"ref_2","first-page":"59","article-title":"Medicinal plants: Future source of new drugs","volume":"4","author":"Shakya","year":"2016","journal-title":"Int. J. Herb. Med."},{"key":"ref_3","first-page":"16","article-title":"A review on various classes of secondary metabolites and biological activities of Lamiaceae (Labiatae) (2002\u20132018)","volume":"4","author":"Hamed","year":"2021","journal-title":"J. Adv. Biomed. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3923\/rjmp.2012.203.213","article-title":"Medicinally potential plants of Labiatae (Lamiaceae) family: An overview","volume":"6","author":"Raja","year":"2012","journal-title":"Res. J. Med. Plant"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Michel, J., Abd Rani, N.Z., and Husain, K. (2020). A review on the potential use of medicinal plants from Asteraceae and Lamiaceae plant family in cardiovascular diseases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00852"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sitarek, P., Merecz-Sadowska, A., \u015aliwi\u0144ski, T., Zajdel, R., and Kowalczyk, T. (2020). An in vitro evaluation of the molecular mechanisms of action of medical plants from the Lamiaceae family as effective sources of active compounds against human cancer cell lines. Cancers, 12.","DOI":"10.3390\/cancers12102957"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Berdowska, I., Zieli\u0144ski, B., Matusiewicz, M., and Fecka, I. (2022). Modulatory impact of Lamiaceae metabolites on apoptosis of human leukemia cells. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.867709"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hiltunen, R., and Holm, Y. (1999). Basil: The genus Ocimum, CRC Press.","DOI":"10.1201\/9780203303771"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.2147\/DMSO.S246996","article-title":"Evaluation of antidiabetic effect of ethanolic leaves extract of Becium grandiflorum Lam. (Lamiaceae) in streptozotocin-induced diabetic mice","volume":"13","author":"Gebremeskel","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1016\/S0031-9422(98)00413-0","article-title":"Triterpenoid saponins from Becium grandiflorum var.  obovatum","volume":"49","author":"Burger","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/S0031-9422(97)00626-2","article-title":"An 8-hydroxylated external flavone and its 8-O-glucoside from Becium grandiflorum","volume":"47","author":"Grayer","year":"1998","journal-title":"Phytochemistry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4314\/epj.v32i2.3","article-title":"In-vivo wound healing activity of 70% ethanol leaf extract of Becium grandiflorum Lam. (Lamiaceae) in mice","volume":"32","author":"Beshir","year":"2016","journal-title":"Ethiop. Pharm. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s13201-021-01373-w","article-title":"Synthesis and characterization of ZnO nanoparticles using aqueous extract of Becium grandiflorum for antimicrobial activity and adsorption of methylene blue","volume":"11","author":"Kahsay","year":"2021","journal-title":"Appl. Water Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1002\/chir.23009","article-title":"Pimarane diterpenes: Natural source, stereochemical configuration, and biological activity","volume":"30","author":"Reveglia","year":"2018","journal-title":"Chirality"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Elhawary, E.A., Mostafa, N.M., Labib, R.M., and Singab, A.N.J.P. (2021). Metabolomic profiles of essential oils from selected rosa varieties and their antimicrobial activities. Plants, 10.","DOI":"10.3390\/plants10081721"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ibrahim, N., Abbas, H., El-Sayed, N.S., and Gad, H.A. (2022). Rosmarinus officinalis L. hexane extract: Phytochemical analysis, nanoencapsulation, and in silico, in vitro, and in vivo anti-photoaging potential evaluation. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-16592-7"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Swilam, N., and Nematallah, K.A. (2020). Polyphenols profile of pomegranate leaves and their role in green synthesis of silver nanoparticles. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-71847-5"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/ptr.7388","article-title":"The natural isoflavone Biochanin-A synergizes 5-fluorouracil anticancer activity in vitro and in vivo in Ehrlich solid-phase carcinoma model","volume":"36","author":"Mahmoud","year":"2022","journal-title":"Phytother. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Abdollah, M.R., Ali, A.A., Elgohary, H.H., and Elmazar, M.M. (2023). Antiangiogenic drugs in combination with seaweed fucoidan: A mechanistic in vitro and in vivo study exploring the VEGF receptor and its downstream signaling molecules in hepatic cancer. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1108992"},{"key":"ref_20","first-page":"2375","article-title":"Ehrlich ascites carcinoma","volume":"10","author":"Ozaslan","year":"2011","journal-title":"Afr. J. Biotechnol."},{"key":"ref_21","unstructured":"Culling, C.F.A. (2013). Handbook of Histopathological and Histochemical Techniques: Including Museum Techniques, Butterworth-Heinemann."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1038\/s41467-019-10363-1","article-title":"Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations","volume":"10","author":"Birkinshaw","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Adzhigirey","year":"2013","journal-title":"J. Comput.-Aided Mol. Des."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel procedure for modeling ligand\/receptor induced fit effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_26","first-page":"9477","article-title":"Chemical composition and effectiveness of Ocimum basilicum L. extracts on the adhesion of Candida albicans and C. dubliniensis on acrylic surfaces of removable orthodontic appliances","volume":"11","author":"Roozbehani","year":"2021","journal-title":"Biointerface Res. Appl. Chem."},{"key":"ref_27","first-page":"172","article-title":"Chemical Composition of Ocimum americanum In Sudan","volume":"5","author":"Mustafa","year":"2019","journal-title":"Res. Pharm. Health Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1039\/C3AY41640B","article-title":"Isolation and purification of ent-pimara-8 (14), 15-diene from engineered Aspergillus nidulans by accelerated solvent extraction combined with HPLC","volume":"6","author":"Bromann","year":"2014","journal-title":"Anal. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1039\/b604174d","article-title":"Diterpenoids from Isodon species and their biological activities","volume":"23","author":"Sun","year":"2006","journal-title":"Nat. Prod. Rep."},{"key":"ref_30","first-page":"69","article-title":"Is Bax\/Bcl-2 ratio considered as a prognostic marker with age and tumor location in colorectal cancer?","volume":"19","author":"Khodapasand","year":"2015","journal-title":"Iran. Biomed. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1073\/pnas.1612322114","article-title":"Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes","volume":"114","author":"Sancho","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1038\/cr.2010.149","article-title":"Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX","volume":"21","author":"Ku","year":"2011","journal-title":"Cell Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hart, P.C., Rajab, I.M., Alebraheem, M., and Potempa, L.A. (2020). C-Reactive protein and cancer\u2014Diagnostic and therapeutic insights. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.595835"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kenchegowda, M., Rahamathulla, M., Hani, U., Begum, M.Y., Guruswamy, S., Osmani, R.A.M., Gowrav, M.P., Alshehri, S., Ghoneim, M.M., and Alshlowi, A. (2021). Smart nanocarriers as an emerging platform for cancer therapy: A review. Molecules, 27.","DOI":"10.3390\/molecules27010146"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, X., Yu, H., Zhang, Y., Lu, X., Wang, B., and Liu, X. (2018). Bioactive pimarane-type diterpenes from marine organisms. Chem. Biodivers., 15.","DOI":"10.1002\/cbdv.201700276"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ye, K., and Ai, H.-l. (2022). Pimarane Diterpenes from Fungi. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101291"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s43450-023-00359-w","article-title":"Cytotoxic Isopimarane Diterpenoids from Kaempferia koratensis Rhizomes","volume":"33","author":"Kongwaen","year":"2023","journal-title":"Rev. Bras. De Farmacogn."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1055\/a-1708-2081","article-title":"In Vitro Cytotoxic and Leishmanicidal Activity of Isolated and Semisynthetic ent-Pimaranes from Aldama arenaria","volume":"88","author":"Conrado","year":"2022","journal-title":"Planta Medica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/aps.2011.202","article-title":"Retinol induces morphological alterations and proliferative focus formation through free radical-mediated activation of multiple signaling pathways","volume":"33","author":"Gelain","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.ctrv.2014.01.001","article-title":"Retinoids and breast cancer: From basic studies to the clinic and back again","volume":"40","author":"Garattini","year":"2014","journal-title":"Cancer Treat. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3149362","DOI":"10.1155\/2018\/3149362","article-title":"Anticancer properties of essential oils and other natural products","volume":"2018","author":"Blowman","year":"2018","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2174\/1568009618666180102105843","article-title":"Anticancer properties of essential oils: An overview","volume":"18","author":"Andrade","year":"2018","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_43","first-page":"207","article-title":"Essential oil with anticancer activity: An overview","volume":"2","author":"Angelini","year":"2018","journal-title":"Anticancer Plants Nat. Prod. Biotechnol. Implements"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1634\/theoncologist.5-6-510","article-title":"The cell cycle","volume":"5","author":"Israels","year":"2000","journal-title":"Oncologist"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41580-021-00404-3","article-title":"Cell cycle control in cancer","volume":"23","author":"Matthews","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1177\/1947601913478972","article-title":"CDK4: A key player in the cell cycle, development, and cancer","volume":"3","author":"Baker","year":"2012","journal-title":"Genes Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature03094","article-title":"G1 cell-cycle control and cancer","volume":"432","year":"2004","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Lindqvist, A., van Zon, W., Karlsson Rosenthal, C., and Wolthuis, R.M.F. (2007). Cyclin B1\u2013Cdk1 activation continues after centrosome separation to control mitotic progression. PLoS Biol., 5.","DOI":"10.1371\/journal.pbio.0050123"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Salanci, \u0160., Vilkov\u00e1, M., Martinez, L., Mirossay, L., Michalkov\u00e1, R., and Moj\u017ei\u0161, J. (2024). The induction of G2\/M phase cell cycle arrest and apoptosis by the chalcone derivative 1C in sensitive and resistant ovarian cancer cells is associated with ROS generation. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147541"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1158\/1940-6207.CAPR-10-0168","article-title":"Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: Implications for chemoprevention","volume":"3","author":"Johnson","year":"2010","journal-title":"Cancer Prev. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1080\/10408398.2016.1203755","article-title":"Ursolic acid, a potential anticancer compound for breast cancer therapy","volume":"58","author":"Yin","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Hasan, M.R., Alotaibi, B.S., Althafar, Z.M., Mujamammi, A.H., and Jameela, J. (2023). An Update on the Therapeutic Anticancer Potential of Ocimum sanctum L.: \u201cElixir of Life\u201d. Molecules, 28.","DOI":"10.3390\/molecules28031193"},{"key":"ref_53","first-page":"647","article-title":"Oridonin induces G2\/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells","volume":"24","author":"Wang","year":"2010","journal-title":"Oncol. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104313","DOI":"10.1016\/j.phrs.2019.104313","article-title":"Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects","volume":"146","author":"Li","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e02772","DOI":"10.1016\/j.heliyon.2019.e02772","article-title":"Ethanolic extract Ocimum sanctum Linn. induces an apoptosis in human lung adenocarcinoma (A549) cells","volume":"5","author":"Wihadmadyatami","year":"2019","journal-title":"Heliyon"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1007\/s00044-012-0113-z","article-title":"Antioxidant properties and chemical constituents of ethanolic extract and its fractions of Ocimum gratissimum","volume":"22","author":"Ouyang","year":"2013","journal-title":"Med. Chem. Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Strzyz, P. (2017). Pulling the apoptotic trigger for necrosis. Nat. Rev. Mol. Cell Biol., 18.","DOI":"10.1038\/nrm.2017.1"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Chan, F.K.-M., Moriwaki, K., and De Rosa, M.J. (2013). Detection of necrosis by release of lactate dehydrogenase activity. Immune Homeostasis: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-62703-290-2_7"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1078\/0065-1281-00601","article-title":"The history of Z-VAD-FMK, a tool for understanding the significance of caspase inhibition","volume":"103","year":"2001","journal-title":"Acta Histochem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1089\/jmf.2014.0008","article-title":"Apoptosis induction by Ocimum sanctum extract in LNCaP prostate cancer cells","volume":"18","author":"Dhandayuthapani","year":"2015","journal-title":"J. Med. Food"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"739093","DOI":"10.1155\/2011\/739093","article-title":"Ocimum gratissimum aqueous extract induces apoptotic signalling in lung adenocarcinoma cell A549","volume":"2011","author":"Chen","year":"2010","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.cbi.2014.10.015","article-title":"Morphological and biochemical alterations activated by antitumor clerodane diterpenes","volume":"222","author":"Ferreira","year":"2014","journal-title":"Chem.-Biol. Interact."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ejmech.2014.05.016","article-title":"Three new cembranoid-type diterpenes from Red Sea soft coral Sarcophyton glaucum: Isolation and antiproliferative activity against HepG2 cells","volume":"81","author":"Alarif","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00210-021-02185-0","article-title":"Antitumor and antiangiogenic effects of Tonantzitlolone B, an uncommon diterpene from Stillingia loranthacea","volume":"395","author":"Batista","year":"2022","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"55863","DOI":"10.18632\/oncotarget.10150","article-title":"Cytoplasmic vacuolization in cell death and survival","volume":"7","author":"Shubin","year":"2016","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.phytol.2012.08.011","article-title":"Evaluation of in vitro anticancer activity of sphaeropsidins A\u2013C, fungal rearranged pimarane diterpenes, and semisynthetic derivatives","volume":"5","author":"Lallemand","year":"2012","journal-title":"Phytochem. Lett."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1164\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:03:17Z","timestamp":1760029397000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1164"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,27]]},"references-count":66,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["nu17071164"],"URL":"https:\/\/doi.org\/10.3390\/nu17071164","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,27]]}}}