{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:50:46Z","timestamp":1787734246336,"version":"build-2784847793"},"reference-count":96,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Biochemistry and Biotechnology, School of Science and Technology, Sefako Makgatho Health Sciences University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Plants have long been used as sources of natural compounds with therapeutic benefits, providing molecules capable of inhibiting multiple kinases. Many medicinal plants are recognized for their anticancer properties and may offer ways to mitigate the adverse effects of conventional cancer treatments. In this study, the potential of Ziziphus mucronata methanol extract as a kinase inhibitor was assessed using the MTT assay, a universal kinase assay, and a human phosphokinase antibody array, along with a GC-MS analysis of volatile anticancer compounds. The MTT assay revealed strong cytotoxicity in A549 cells, with an IC50 of 31.25 \u00b5g\/mL, while HeLa cells showed weaker cytotoxicity with an IC50 of 125 \u00b5g\/mL. In comparison, paclitaxel exhibited potent inhibitory effects on A549 cells (IC50 of 31.25 \u00b5g\/mL) and moderate inhibition on HeLa cells (IC50 of 65 \u00b5g\/mL). Enzyme activity, measured by ADP production in the ADP-Glo assay, indicated that the extract inhibited protein kinase activity in both A549 and HeLa cells after 24 h of treatment. Additionally, the human phosphokinase antibody array, which includes 44 pre-spotted kinases, showed that the extract downregulated multiple phosphorylated kinases in both cell lines. Some of the affected kinases, such as TOR, Fyn, HcK, Fgr, STAT5b, PLC-\u03b31, p38\u03b1, ERK1\/2, AMPKA, Akt1\/2, GSK-3\u03b1\/\u03b2, MSK1\/2, CREB, RSK1\/2\/3, PLC-\u03b31, and STAT5a are critical regulators of various cellular processes, including apoptosis, differentiation, and proliferation. The findings of this study suggest that extract from Z. mucronata may have the capacity to regulate protein kinase activity, highlighting their significant potential as growth inhibitors for cancer cells.<\/jats:p>","DOI":"10.3390\/plants14030395","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T06:47:29Z","timestamp":1738046849000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Inhibition of Kinase Activity and In Vitro Downregulation of the Protein Kinases in Lung Cancer and Cervical Cancer Cell Lines and the Identified Known Anticancer Compounds of Ziziphus mucronata"],"prefix":"10.3390","volume":"14","author":[{"given":"Themba","family":"Sambo","sequence":"first","affiliation":[{"name":"Department of Biochemistry & Biotechnology, School of Science and Technology, Sefako Makgatho Health Sciences University, Ga-Rankuwa 0208, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-2874","authenticated-orcid":false,"given":"Emelinah","family":"Mathe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Biotechnology, School of Science and Technology, Sefako Makgatho Health Sciences University, Ga-Rankuwa 0208, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4799-7437","authenticated-orcid":false,"given":"Leswheni","family":"Shai","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences, Tshwane University of Technology, Pretoria 0183, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5096-5367","authenticated-orcid":false,"given":"Sipho","family":"Mapfumari","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Sefako Makgatho Health Sciences University, Ga-Rankuwa 0208, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8059-1941","authenticated-orcid":false,"given":"Stanley","family":"Gololo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry & Biotechnology, School of Science and Technology, Sefako Makgatho Health Sciences University, Ga-Rankuwa 0208, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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