{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T19:05:57Z","timestamp":1788375957463,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of T\u00fcrkiye","doi-asserted-by":"publisher","award":["1919B012409764"],"award-info":[{"award-number":["1919B012409764"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"award":["1919B012409764"],"award-info":[{"award-number":["1919B012409764"]}],"id":[{"id":"https:\/\/ror.org\/04w9kkr77","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast and prostate cancers remain among the most prevalent epithelial malignancies worldwide, and conventional treatments often lack tumor selectivity. Aloin, an anthraquinone glycoside derived from Aloe vera, has demonstrated promising anticancer properties. This study investigated the differential cytotoxic and apoptotic effects of Aloin under in vitro conditions in MCF-7 (breast cancer) and PC-3 (prostate cancer) cell lines compared with normal prostate epithelial cells (PNT-A1). Cells were treated with Aloin (1000\u20131500 \u00b5g\/mL); cytotoxicity was assessed by CCK-8 assay, apoptotic morphology by DIC microscopy, protein expression by immunofluorescence with quantitative CTCF analysis (BAX, Caspase-3, Caspase-8, Caspase-9), and gene expression by qRT-PCR (2\u2212\u0394\u0394Ct method). An integrated log2 fold change heatmap, pathway enrichment analysis across three independent databases (KEGG 2026, Reactome 2024, WikiPathways 2024), and STRING v12.0-based protein\u2013protein interaction (PPI) network were constructed. Aloin exerted significant dose-dependent cytotoxicity in both cancer cell lines, while PNT-A1 viability exceeded 50% across all concentrations (Selectivity Index &gt; 1.30 for MCF-7 at 48 h). Immunofluorescence and qRT-PCR confirmed significant upregulation of BAX (up to 6.14\u00d7), CASP8 (up to 15.51\u00d7), CASP9 (up to 9.27\u00d7), and CASP3 (3.03\u00d7 in PC-3), indicating concurrent activation of intrinsic and extrinsic apoptotic pathways, while all genes remained unchanged in PNT-A1 cells. Pathway enrichment analysis confirmed that these genes are statistically central nodes in conserved apoptotic signaling networks (adj. p &lt; 10\u22129). To the best of our knowledge, this is the first in vitro characterization of Aloin-induced pro-apoptotic activity in prostate cancer cells, establishing a mechanistic foundation for further investigation of this phytochemical in epithelial-derived cancer models.<\/jats:p>","DOI":"10.3390\/ijms27125501","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T07:33:54Z","timestamp":1781768034000},"page":"5501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Aloin Induces Selective Cytotoxicity and Apoptotic Pathway Activation in Breast and Prostate Cancer Cells via Intrinsic and Extrinsic Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3882-0728","authenticated-orcid":false,"given":"Mohammadreza","family":"Dastouri","sequence":"first","affiliation":[{"name":"Department of Medical Biology, School of Medicine, Ankara Medipol University, Ankara 06570, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buse","family":"Sanli","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, School of Medicine, Ankara Medipol University, Ankara 06570, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, October 24). 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