{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:06:05Z","timestamp":1791324365687,"version":"4.3.1"},"reference-count":50,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Metabolic regulation of cancer cell growth via AMP-activated protein kinase (AMPK) activation is a widely studied strategy for cancer treatment, including leukemias. Recent notions that naturally occurring compounds might have AMPK activity led to the search for nutraceuticals with potential AMPK-stimulating activity. We found that hydroxycitric acid (HCA), a natural, safe bioactive from the plant Garcinia gummi-gutta (cambogia), has potent AMPK activity in chronic myelogenous leukemia (CML) cell line K562. HCA is a known competitive inhibitor of ATP citrate lyase (ACLY) and is widely used as a weight loss inducer. We found that HCA was able to inhibit the growth of K562 cells in in vitro and in vivo xenograft models. At the mechanistic level, we identified a direct interaction between AMPK and ACLY that seems to be sensitive to HCA treatment. Additionally, HCA treatment resulted in the co-activation of AMPK and the mammalian target of rapamycin (mTOR) pathways. Moreover, we found an enhanced unfolded protein response as observed by activation of the eIF2\u03b1\/ATF4 pathway that could explain the induction of cell cycle arrest at the G2\/M phase and DNA fragmentation upon HCA treatment in K562 cells. Overall, these findings suggest HCA as a nutraceutical approach for the treatment of CMLs.<\/jats:p>","DOI":"10.3390\/nu14132669","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:07:02Z","timestamp":1656374822000},"page":"2669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Hydroxycitric Acid Inhibits Chronic Myelogenous Leukemia Growth through Activation of AMPK and mTOR Pathway"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5764-6775","authenticated-orcid":false,"given":"Doriana","family":"Verrelli","sequence":"first","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Dallera","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Stendardo","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Monzani","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9038-7768","authenticated-orcid":false,"given":"Sebastiano","family":"Pasqualato","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Giorgio","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"},{"name":"Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58\/B, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Pallavi","sequence":"additional","affiliation":[{"name":"IRCCS European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.cmet.2014.09.013","article-title":"AMPK\u2014Sensing Energy While Talking to Other Signaling Pathways","volume":"20","author":"Hardie","year":"2014","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A Nutrient and Energy Sensor That Maintains Energy Homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. 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