{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:07Z","timestamp":1787028547132,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,21]],"date-time":"2024-07-21T00:00:00Z","timestamp":1721520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National University of Singapore-Leeward Pacific Pte Ltd. research collaboration","award":["R-148-000-172-592"],"award-info":[{"award-number":["R-148-000-172-592"]}]},{"name":"National University of Singapore-Leeward Pacific Pte Ltd. research collaboration","award":["SRG-OPN-06-2023"],"award-info":[{"award-number":["SRG-OPN-06-2023"]}]},{"name":"National University of Singapore-Leeward Pacific Pte Ltd. research collaboration","award":["AM\/TP020\/2018"],"award-info":[{"award-number":["AM\/TP020\/2018"]}]},{"name":"National University of Singapore-Leeward Pacific Pte Ltd. research collaboration","award":["NMRC\/CG\/C012A\/2017"],"award-info":[{"award-number":["NMRC\/CG\/C012A\/2017"]}]},{"name":"SGH Research Grant","award":["R-148-000-172-592"],"award-info":[{"award-number":["R-148-000-172-592"]}]},{"name":"SGH Research Grant","award":["SRG-OPN-06-2023"],"award-info":[{"award-number":["SRG-OPN-06-2023"]}]},{"name":"SGH Research Grant","award":["AM\/TP020\/2018"],"award-info":[{"award-number":["AM\/TP020\/2018"]}]},{"name":"SGH Research Grant","award":["NMRC\/CG\/C012A\/2017"],"award-info":[{"award-number":["NMRC\/CG\/C012A\/2017"]}]},{"name":"Academia Medical Research Grant","award":["R-148-000-172-592"],"award-info":[{"award-number":["R-148-000-172-592"]}]},{"name":"Academia Medical Research Grant","award":["SRG-OPN-06-2023"],"award-info":[{"award-number":["SRG-OPN-06-2023"]}]},{"name":"Academia Medical Research Grant","award":["AM\/TP020\/2018"],"award-info":[{"award-number":["AM\/TP020\/2018"]}]},{"name":"Academia Medical Research Grant","award":["NMRC\/CG\/C012A\/2017"],"award-info":[{"award-number":["NMRC\/CG\/C012A\/2017"]}]},{"name":"NMRC Centre Grant Programme-Targeted Therapy for Blood Cancer","award":["R-148-000-172-592"],"award-info":[{"award-number":["R-148-000-172-592"]}]},{"name":"NMRC Centre Grant Programme-Targeted Therapy for Blood Cancer","award":["SRG-OPN-06-2023"],"award-info":[{"award-number":["SRG-OPN-06-2023"]}]},{"name":"NMRC Centre Grant Programme-Targeted Therapy for Blood Cancer","award":["AM\/TP020\/2018"],"award-info":[{"award-number":["AM\/TP020\/2018"]}]},{"name":"NMRC Centre Grant Programme-Targeted Therapy for Blood Cancer","award":["NMRC\/CG\/C012A\/2017"],"award-info":[{"award-number":["NMRC\/CG\/C012A\/2017"]}]},{"name":"National University of Singapore Provost Industrial PhD Programme Research Scholarship","award":["R-148-000-172-592"],"award-info":[{"award-number":["R-148-000-172-592"]}]},{"name":"National University of Singapore Provost Industrial PhD Programme Research Scholarship","award":["SRG-OPN-06-2023"],"award-info":[{"award-number":["SRG-OPN-06-2023"]}]},{"name":"National University of Singapore Provost Industrial PhD Programme Research Scholarship","award":["AM\/TP020\/2018"],"award-info":[{"award-number":["AM\/TP020\/2018"]}]},{"name":"National University of Singapore Provost Industrial PhD Programme Research Scholarship","award":["NMRC\/CG\/C012A\/2017"],"award-info":[{"award-number":["NMRC\/CG\/C012A\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of Leea indica, a local medicinal plant, in CML. Using high-performance liquid chromatography\u2013electrospray ionization\u2013mass spectrometry, a chemical constituent from L. indica extract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid from L. indica inhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34+ cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK\/MAPK, FLT3 and JAK\/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficient \u03c10 cells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential of L. indica in CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.<\/jats:p>","DOI":"10.3390\/ijms25147958","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T07:57:23Z","timestamp":1721721443000},"page":"7958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gallic Acid Enhances the Efficacy of BCR::ABL1 Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia through Inhibition of Mitochondrial Respiration and Modulation of Oncogenic Signaling Pathways"],"prefix":"10.3390","volume":"25","author":[{"given":"Wei","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, National Cancer Centre Singapore, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6717-7837","authenticated-orcid":false,"given":"Colin","family":"Sng","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, National Cancer Centre Singapore, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hui","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, National Cancer Centre Singapore, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Hui","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, National Cancer Centre Singapore, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeh-Ching","family":"Linn","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, National Cancer Centre Singapore, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soek-Ying","family":"Neo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7543-0943","authenticated-orcid":false,"given":"Yin-Yin","family":"Siew","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-9245","authenticated-orcid":false,"given":"Hwee-Ling","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore 117543, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Chuah","sequence":"additional","affiliation":[{"name":"Department of Haematology, Singapore General Hospital, National Cancer Centre Singapore, Singapore 169608, Singapore"},{"name":"Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrc1567","article-title":"Mechanisms of BCR-ABL in the pathogenesis of chronic myelogenous leukaemia","volume":"5","author":"Ren","year":"2005","journal-title":"Nat. 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