{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:38:41Z","timestamp":1781811521255,"version":"3.54.5"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science, Research and Innovation Fund"},{"name":"College of Medicine and Public Health, Ubon Ratchathani University"},{"name":"National Research Center of Thailand (NRCT)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Abnormal cell proliferation and accumulation of fluid-filled cysts along the nephrons in polycystic kidney disease (PKD) could lead to a decline in renal function and eventual end-stage renal disease (ESRD). Gambogic acid (GA), a xanthone compound extracted from the brownish resin of the Garcinia hanburyi tree, exhibits various pharmacological properties, including anti-inflammation, antioxidant, anti-proliferation, and anti-cancer activity. However, its effect on inhibiting cell proliferation in PKD is still unknown. This study aimed to determine the pharmacological effects and detailed mechanisms of GA in slowing an in vitro cyst growth model of PKD. The results showed that GA (0.25\u20132.5 \u03bcM) significantly retarded MDCK cyst growth and cyst formation in a dose-dependent manner, without cytotoxicity. Using the BrdU cell proliferation assay, it was found that GA (0.5\u20132.5 \u03bcM) suppressed MDCK and Pkd1 mutant cell proliferation. In addition, GA (0.5\u20132.5 \u03bcM) strongly inhibited phosphorylation of ERK1\/2 and S6K expression and upregulated the activation of phosphorylation of AMPK, both in MDCK cells and Pkd1 mutant cells. Taken together, these findings suggested that GA could retard MDCK cyst enlargement, at least in part by inhibiting the cell proliferation pathway. GA could be a natural plant-based drug candidate for ADPKD intervention.<\/jats:p>","DOI":"10.3390\/molecules27123837","type":"journal-article","created":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T01:39:54Z","timestamp":1655257194000},"page":"3837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Potential Application of Gambogic Acid for Retarding Renal Cyst Progression in Polycystic Kidney Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8337-1979","authenticated-orcid":false,"given":"Nutchanard","family":"Khunpatee","sequence":"first","affiliation":[{"name":"Biomedical Science Program, College of Medicine and Public Health, Ubon Ratchathani University, Sathonlamark Road, Warin Chamrap, Ubon Ratchathani 34190, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanit","family":"Bhukhai","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varanuj","family":"Chatsudthipong","sequence":"additional","affiliation":[{"name":"Research Center of Transport Proteins for Medical Innovation, Faculty of Science, Mahidol University, Rama VI Road, Rajathevi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2684-4071","authenticated-orcid":false,"given":"Chaowalit","family":"Yuajit","sequence":"additional","affiliation":[{"name":"College of Medicine and Public Health, Ubon Ratchathani University, Sathonlamark Road, Warin Chamrap, Ubon Ratchathani 34190, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41572-018-0047-y","article-title":"Polycystic kidney disease","volume":"4","author":"Bergmann","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1681\/ASN.2018060590","article-title":"A Practical Guide for Treatment of Rapidly Progressive ADPKD with Tolvaptan","volume":"29","author":"Chebib","year":"2018","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lakhia, R., Mishra, A., Biggers, L., Malladi, V., Cobo-Stark, P., Hajarnis, S., and Patel, V. (2021). Enhancer and super-enhancer landscape in polycystic kidney disease. bioRxiv.","DOI":"10.1101\/2021.11.19.469306"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14395","DOI":"10.1038\/ncomms14395","article-title":"microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism","volume":"8","author":"Hajarnis","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1083\/jcb.201006173","article-title":"The cell biology of polycystic kidney disease","volume":"191","author":"Chapin","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.bbadis.2010.11.005","article-title":"Cyclic AMP-mediated cyst expansion","volume":"1812","author":"Wallace","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/hmg\/ddn039","article-title":"Cyst formation and activation of the extracellular regulated kinase pathway after kidney specific inactivation of Pkd1","volume":"17","author":"Shibazaki","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5466","DOI":"10.1073\/pnas.0509694103","article-title":"The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease","volume":"103","author":"Shillingford","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e95874","DOI":"10.1172\/jci.insight.95874","article-title":"Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD","volume":"3","author":"Li","year":"2018","journal-title":"JCI Insight"},{"key":"ref_10","first-page":"S97","article-title":"Nutraceutical for Autosomal Dominant Polycystic Kidney Disease Therapy","volume":"99","author":"Yuajit","year":"2016","journal-title":"J. Med. Assoc. Thail."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1002\/ardp.19662990911","article-title":"The constitution of gambogic acid and its isomerization. 4. Chemistry of gum-resin","volume":"299","author":"Liesenklas","year":"1966","journal-title":"Arch. Pharm. Ber. Dtsch. Pharm. Ges."},{"key":"ref_12","first-page":"1747","article-title":"Gambogic acid inhibits proliferation and induces apoptosis of human acute T-cell leukemia cells by inducing autophagy and downregulating \u03b2-catenin signaling pathway: Mechanisms underlying the effect of Gambogic acid on T-ALL cells","volume":"44","author":"Wang","year":"2020","journal-title":"Oncol. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10385","DOI":"10.2147\/IJN.S277645","article-title":"Gambogic Acid as a Candidate for Cancer Therapy: A Review","volume":"15","author":"Liu","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"172719","DOI":"10.1016\/j.ejphar.2019.172719","article-title":"Gambogic acid exhibits anti-metastatic activity on malignant melanoma mainly through inhibition of PI3K\/Akt and ERK signaling pathways","volume":"864","author":"Li","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1158\/0008-5472.CAN-07-5944","article-title":"Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing vascular endothelial growth factor receptor 2 signaling","volume":"68","author":"Yi","year":"2008","journal-title":"Cancer Res."},{"key":"ref_16","first-page":"4791","article-title":"Anti-inflammatory effects of gambogic acid in murine collagen--induced arthritis through PI3K\/Akt signaling pathway","volume":"17","author":"Wang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.kjms.2017.06.013","article-title":"Gambogic acid improves non-small cell lung cancer progression by inhibition of mTOR signaling pathway","volume":"33","author":"Zhao","year":"2017","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5568","DOI":"10.7150\/jca.41115","article-title":"Gambogic acid affects ESCC progression through regulation of PI3K\/AKT\/mTOR signal pathway","volume":"11","author":"Yu","year":"2020","journal-title":"J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.bbrc.2013.04.099","article-title":"Gambogic acid induces EGFR degradation and Akt\/mTORC1 inhibition through AMPK dependent-LRIG1 upregulation in cultured U87 glioma cells","volume":"435","author":"He","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.biopha.2017.07.165","article-title":"Steviol stabilizes polycystin 1 expression and promotes lysosomal degradation of CFTR and beta-catenin proteins in renal epithelial cells","volume":"94","author":"Yuajit","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"109468","DOI":"10.1016\/j.cellsig.2019.109468","article-title":"The PI3K\/Akt\/mTOR pathway in polycystic kidney disease: A complex interaction with polycystins and primary cilium","volume":"66","author":"Margaria","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1073\/pnas.1011498108","article-title":"Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis","volume":"108","author":"Takiar","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Pathomthongtaweechai, N., Soodvilai, S., Pichyangkura, R., and Muanprasat, C. (2020). Novel Potential Application of Chitosan Oligosaccharide for Attenuation of Renal Cyst Growth in the Treatment of Polycystic Kidney Disease. Molecules, 25.","DOI":"10.3390\/molecules25235589"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1007\/s10157-021-02080-1","article-title":"A chalcone derivative retards renal cyst enlargement by inhibiting fluid secretion and cell proliferation in an in vitro model of polycystic kidney disease","volume":"25","author":"Veeraphan","year":"2021","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1016\/j.bcp.2014.01.038","article-title":"Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease","volume":"88","author":"Yuajit","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"F1193","DOI":"10.1152\/ajprenal.00419.2010","article-title":"Curcumin inhibits cystogenesis by simultaneous interference of multiple signaling pathways: In vivo evidence from a Pkd1-deletion model","volume":"300","author":"Leonhard","year":"2011","journal-title":"Am. J. Physiology. Ren. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"F1234","DOI":"10.1152\/ajprenal.00356.2011","article-title":"Ginkgolide B inhibits renal cyst development in in vitro and in vivo cyst models","volume":"302","author":"Zhou","year":"2012","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Yuajit, C., Homvisasevongsa, S., Chatsudthipong, L., Soodvilai, S., Muanprasat, C., and Chatsudthipong, V. (2013). Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0058871"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kale, V.P., Gilhooley, P.J., Phadtare, S., Nabavizadeh, A., and Pandey, M.K. (2018). Role of Gambogic Acid in Chemosensitization of Cancer. Role of Nutraceuticals in Cancer Chemosensitization, Elsevier.","DOI":"10.1016\/B978-0-12-812373-7.00008-5"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1139\/O08-104","article-title":"Anti-invasive effect of gambogic acid in MDA-MB-231 human breast carcinoma cells","volume":"86","author":"Qi","year":"2008","journal-title":"Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"109704","DOI":"10.1016\/j.cellsig.2020.109704","article-title":"Targeting AMP-activated protein kinase (AMPK) for treatment of autosomal dominant polycystic kidney disease","volume":"73","author":"Song","year":"2020","journal-title":"Cell. Signal."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113635","DOI":"10.1016\/j.bcp.2019.113635","article-title":"Involvement of E-cadherin\/AMPK\/mTOR axis in LKB1-induced sensitivity of non-small cell lung cancer to gambogic acid","volume":"169","author":"Li","year":"2019","journal-title":"Biochem. Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3837\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:31:40Z","timestamp":1760139100000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/12\/3837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,15]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["molecules27123837"],"URL":"https:\/\/doi.org\/10.3390\/molecules27123837","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,15]]}}}