{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T07:58:16Z","timestamp":1790582296252,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cancer cells undergo metabolic reprogramming to sustain proliferation, resist apoptosis, and adapt to oxidative stress. In the present study, we comparatively evaluated the anticancer effects of four medicinal plant extracts (\n                    <jats:italic>Inula helenium, Hypericum alpestre, Rumex obtusifolius<\/jats:italic>\n                    , and\n                    <jats:italic>Alchemilla smirnovii<\/jats:italic>\n                    ) on HeLa cervical cancer cells, with particular emphasis on oxidative stress,\n                    <jats:sc>l<\/jats:sc>\n                    \u2010arginine metabolism, and cellular energy pathways. Cell viability was assessed using the MTT (3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyltetrazolium bromide) assay, while biochemical colorimetric methods were used to determine nitric oxide production, arginase and nitric oxide synthase activities, malondialdehyde levels, superoxide dismutase and catalase activities, proline content, and key glycolytic metabolites. Nuclear morphology changes consistent with apoptotic features were examined by Hoechst 33258 staining. All tested extracts exhibited cytotoxic effects in HeLa cells in a time\u2010 and concentration\u2010dependent manner, which were further enhanced when combined with the metabolic inhibitors l\u2010NAME (N\u03c9\u2010nitro\u2010l\u2010arginine methyl ester) or nor\u2010NOHA (N\u03c9\u2010hydroxy\u2010nor\u2010l\u2010arginine).\n                    <jats:italic>Inula helenium<\/jats:italic>\n                    showed the strongest potentiation in combination treatments. Several extracts significantly decreased arginase activity while increasing nitric oxide synthase activity and nitrite levels, indicating modulation of l\u2010arginine metabolism. Treatments also increased malondialdehyde levels and stimulated antioxidant enzyme activities, consistent with redox imbalance and oxidative stress\u2013mediated cytotoxicity. In addition,\n                    <jats:italic>Inula helenium<\/jats:italic>\n                    and\n                    <jats:italic>Alchemilla smirnovii<\/jats:italic>\n                    reduced intracellular glucose, pyruvate, and lactate concentrations, suggesting partial modulation of glycolytic metabolism. Fluorescence microscopy revealed chromatin condensation, nuclear fragmentation, and apoptotic body formation, particularly after treatment with\n                    <jats:italic>Hypericum alpestre<\/jats:italic>\n                    and\n                    <jats:italic>Rumex obtusifolius<\/jats:italic>\n                    . These findings demonstrate that selected medicinal plant extracts exert cytotoxic effects by simultaneously modulating oxidative stress, amino acid metabolism, and energy pathways in cervical cancer cells. The investigated plants may represent promising sources of bioactive compounds for the development of complementary metabolic anticancer strategies.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70307","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:05:42Z","timestamp":1789142742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytotoxic Effects of Medicinal Plant Extracts on HeLa Cells via Redox Imbalance, L\u2010Arginine Metabolic Reprogramming, and Glycolytic Suppression"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7676-5038","authenticated-orcid":false,"given":"Mery","family":"Kocharyan","sequence":"first","affiliation":[{"name":"Research Institute of Biology Yerevan State University, Alex Manoogian Yerevan Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-6314","authenticated-orcid":false,"given":"Gohar","family":"Sevoyan","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Tissue Engineering of L.A. Orbeli Institute of Physiology of NAS RA Yerevan Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6749-4470","authenticated-orcid":false,"given":"Hasmik","family":"Karapetyan","sequence":"additional","affiliation":[{"name":"Research Institute of Biology Yerevan State University, Alex Manoogian Yerevan Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2720-0355","authenticated-orcid":false,"given":"Anzhela","family":"Sargsyan","sequence":"additional","affiliation":[{"name":"Research Institute of Biology Yerevan State University, Alex Manoogian Yerevan Armenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8585-5539","authenticated-orcid":false,"given":"Mikayel","family":"Ginovyan","sequence":"additional","affiliation":[{"name":"Research Institute of Biology Yerevan State University, Alex Manoogian Yerevan 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