{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T14:55:25Z","timestamp":1774536925314,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institute of Health Research (CIHR)\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t              https:\/\/ror.org\/01gavpb45","award":["PJT-183802-2022"],"award-info":[{"award-number":["PJT-183802-2022"]}]},{"name":"CHU de Qu\u00e9bec"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: The aminosteroid RM-581 exhibits strong antiproliferative activity against cell lines from more than 10 solid tumor cancers, including some with poor prognoses. However, RM-581\u2019s impact has never been assessed on leukemia. Methods: Cellular responses to RM-581 were evaluated using complementary approaches. Cytotoxicity was quantified using MTS-based viability assays and drug interactions were analyzed according to the Chou-Talalay method. Flow cytometry was employed to assess apoptosis, cell cycle distribution and effects on lymphocytes subpopulations. The transcriptomic profile was investigated by mRNA sequencing to identify differentially expressed genes and associated pathways. Results: Its evaluation on six leukemia cell lines (HL-60, THP-1, JURKAT, K-562, HG-3 and JVM-2) showed that RM-581 efficiently blocked the proliferation of leukemia cells. In healthy peripheral blood lymphocytes, flow cytometry revealed a significant impact on T lymphocytes (CD3+), particularly cytotoxic T cells (CD8+), at 50 \u00b5M. In THP-1 cells, an acute monocytic leukemia cell line, RM-581 triggered apoptosis and induced G0\/G1 cell cycle arrest, which was confirmed with a transcriptomic analysis of enriched pathways. The role of RM-581 as an endoplasmic reticulum (ER) stress aggravator was confirmed by observing an increase in ER stress markers, such as BIP (GRP-78), CHOP and HERP, and in unfolded protein response (UPR) effectors (PERK, IRE1\u03b1 and ATF6). Conclusions: This study demonstrates that RM-581 could be a promising candidate to treat leukemia, notably through the induction of ER-stress mediated apoptosis.<\/jats:p>","DOI":"10.3390\/cancers18071078","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:48:41Z","timestamp":1774532921000},"page":"1078","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aminosteroid RM-581 Induces G0\/G1 Arrest and Endoplasmic Reticulum Stress-Mediated Apoptosis in Human Acute and Chronic Leukemia Cell Lines"],"prefix":"10.3390","volume":"18","author":[{"given":"Maude","family":"Fleury","sequence":"first","affiliation":[{"name":"Endocrinology and Nephrology Unit, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Pavillon CHUL, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"Universit\u00e9 Laval Cancer Research Center, Qu\u00e9bec, QC G1R 3S3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Roy","sequence":"additional","affiliation":[{"name":"Endocrinology and Nephrology Unit, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Pavillon CHUL, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-1653","authenticated-orcid":false,"given":"Ren\u00e9","family":"Maltais","sequence":"additional","affiliation":[{"name":"Endocrinology and Nephrology Unit, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Pavillon CHUL, Qu\u00e9bec, QC G1V 4G2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8012-4641","authenticated-orcid":false,"given":"Francine","family":"Durocher","sequence":"additional","affiliation":[{"name":"Endocrinology and Nephrology Unit, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Pavillon CHUL, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"Universit\u00e9 Laval Cancer Research Center, Qu\u00e9bec, QC G1R 3S3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Poirier","sequence":"additional","affiliation":[{"name":"Endocrinology and Nephrology Unit, CHU de Qu\u00e9bec-Universit\u00e9 Laval Research Center, Pavillon CHUL, Qu\u00e9bec, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"},{"name":"Universit\u00e9 Laval Cancer Research Center, Qu\u00e9bec, QC G1R 3S3, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"ref_1","unstructured":"Canadian Cancer Statistics Advisory Committee in Collaboration with the Canadian Cancer Society, Statistics Canada, and the Public Health Agency of Canada (2025, September 15). 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