{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:22Z","timestamp":1786121362167,"version":"build-2736575974"},"reference-count":187,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Plant-derived natural products remain a major source of anticancer chemical diversity, yet much of the preclinical literature still describes their activity through compound-centered readouts such as IC50 values, reactive oxygen species generation, mitochondrial depolarization, BCL-2-family remodeling, caspase activation, and PI3K\/Akt or NF-\u03baB inhibition. Although informative, these mechanisms do not fully explain why the same phytochemical induces apoptosis in some cancer cells, and cytostasis or adaptation in others, while normal cells frequently activate cytoprotective responses. Rather than replacing conventional compound-centered approaches, we integrate established concepts into a complementary vulnerability-state framework for interpreting plant-derived natural-product-induced selective apoptosis. In this framework, selective apoptosis occurs when phytochemical-induced stress intersects with pre-existing cancer-cell vulnerabilities, overwhelms adaptive buffering, and remains below the injury threshold of normal cells. We organize current evidence around redox imbalance, mitochondrial priming, membrane remodeling, ion-channel and cell-volume dysregulation, and survival-pathway addiction, emphasizing that pathway modulation becomes mechanistically meaningful when linked to differential cellular sensitivity. We further highlight membrane\u2013ion biology as an underexplored contributor to phytochemical responses and discuss how chemical standardization, orthogonal cell-death assays, matched normal-cell models, organoids, and pharmacokinetic\/pharmacodynamic considerations can advance the field from descriptive cytotoxicity toward mechanism-informed phytopharmacology.<\/jats:p>","DOI":"10.3390\/ph19081233","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"1233","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plant-Derived Natural Products and Selective Apoptosis: A Cancer-Cell Vulnerability-State Framework from Redox Imbalance to Membrane\u2013Ion Dysregulation"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7288-1917","authenticated-orcid":false,"given":"Nurzhanyat","family":"Ablaikhanova","sequence":"first","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulmira","family":"Assan","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty 050040, Kazakhstan"},{"name":"Department of Normal Physiology with a Course of Biophysics, S.D. Asfendiyarov Kazakh National Medical University, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranokhon","family":"Kurbannazarova","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Physiology, Institute of Biophysics and Biochemistry, National University of Uzbekistan, Tashkent 100174, Uzbekistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5204-4748","authenticated-orcid":false,"given":"Botagoz","family":"Ussipbek","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arailym","family":"Yessenbekova","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akzhunis","family":"Zhumash","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziza","family":"Bekenova","sequence":"additional","affiliation":[{"name":"Department of Normal Physiology with a Course of Biophysics, S.D. Asfendiyarov Kazakh National Medical University, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzhan","family":"Kulbayeva","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Biomedicine and Neuroscience, Farabi University, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9309-1443","authenticated-orcid":false,"given":"Beibarys","family":"Mukhitdin","sequence":"additional","affiliation":[{"name":"Laboratory of Environmental Physiology of Humans and Animals, Institute of Genetics and Physiology, Almaty 050060, Kazakhstan"},{"name":"Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5390-4623","authenticated-orcid":false,"given":"Aidos","family":"Bolatov","sequence":"additional","affiliation":[{"name":"Guangdong Key Laboratory for Genome Stability & Disease Prevention and Carson International Cancer Center, Marshall Laboratory of Biomedical Engineering, Shenzhen University Medical School, Shenzhen University, Shenzhen 518037, China"},{"name":"Department of Science, \u201cUniversity Medical Center\u201d Corporate Fund, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Choudhari, A.S., Mandave, P.C., Deshpande, M., Ranjekar, P., and Prakash, O. 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