{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T10:45:35Z","timestamp":1776509135022,"version":"3.51.2"},"reference-count":91,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T00:00:00Z","timestamp":1627516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2021R1I1A2060024"],"award-info":[{"award-number":["NRF-2021R1I1A2060024"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pyrimethamine (Pyri) is being used in combination with other medications to treat serious parasitic infections of the body, brain, or eye and to also reduce toxoplasmosis infection in the patients with HIV infection. Additionally, Pyri can display significant anti-cancer potential in different tumor models, but the possible mode of its actions remains unclear. Hence, in this study, the possible anti-tumoral impact of Pyri on human chronic myeloid leukemia (CML) was deciphered. Pyri inhibited cell growth in various types of tumor cells and exhibited a marked inhibitory action on CML cells. In addition to apoptosis, Pyri also triggered sustained autophagy. Targeted inhibition of autophagy sensitized the tumor cells to Pyri-induced apoptotic cell death. Moreover, the activation of signal transducer and activator of transcription 5 (STAT5) and its downstream target gene Bcl-2 was attenuated by Pyri. Accordingly, small interfering RNA (siRNA)-mediated STAT5 knockdown augmented Pyri-induced autophagy and apoptosis and promoted the suppressive action of Pyri on cell viability. Moreover, ectopic overexpression of Bcl-2 protected the cells from Pyri-mediated autophagy and apoptosis. Overall, the data indicated that the attenuation of STAT5-Bcl-2 cascade by Pyri can regulate its growth inhibitory properties by simultaneously targeting both apoptosis and autophagy cell death mechanism(s).<\/jats:p>","DOI":"10.3390\/ijms22158147","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T10:47:46Z","timestamp":1627555666000},"page":"8147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Pyrimethamine Modulates Interplay between Apoptosis and Autophagy in Chronic Myelogenous Leukemia Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Young Yun","family":"Jung","sequence":"first","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chulwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9210-1401","authenticated-orcid":false,"given":"In Jin","family":"Ha","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0060-5777","authenticated-orcid":false,"given":"Seok-Geun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"},{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhee","family":"Lee","sequence":"additional","affiliation":[{"name":"Korean Medicine Clinical Trial Center (K-CTC), Korean Medicine Hospital, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0568-9738","authenticated-orcid":false,"given":"Jae-Young","family":"Um","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0612","authenticated-orcid":false,"given":"Kwang Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(04)16412-X","article-title":"Toxoplasmosis","volume":"363","author":"Montoya","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"USPHS\/IDSA Prevention of Opportunistic Infections Working Group (2000). 1999 USPHS\/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. 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