{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:02:44Z","timestamp":1773064964317,"version":"3.50.1"},"reference-count":84,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chulalongkorn University","award":["90th Anniversary of Chulalongkorn University"],"award-info":[{"award-number":["90th Anniversary of Chulalongkorn University"]}]},{"name":"Chulalongkorn University","award":["Ratchadaphiseksomphot Endowment Fund (grant no. CU_GR_62_20_33_01)"],"award-info":[{"award-number":["Ratchadaphiseksomphot Endowment Fund (grant no. CU_GR_62_20_33_01)"]}]},{"name":"National Research Council of Thailand (NRCT)","award":["Mid-Career Research Grant (RSA 6280009)"],"award-info":[{"award-number":["Mid-Career Research Grant (RSA 6280009)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>It has been recognized that cancer stem-like cells (CSCs) in tumor tissue crucially contribute to therapeutic failure, resulting in a high mortality rate in lung cancer patients. Due to their stem-like features of self-renewal and tumor formation, CSCs can lead to drug resistance and tumor recurrence. Herein, the suppressive effect of jorunnamycin A, a bistetrahydroisoquinolinequinone isolated from Thai blue sponge Xestospongia sp., on cancer spheroid initiation and self-renewal in the CSCs of human lung cancer cells is revealed. The depletion of stemness transcription factors, including Nanog, Oct-4, and Sox2 in the lung CSC-enriched population treated with jorunnamycin A (0.5 \u03bcM), resulted from the activation of GSK-3\u03b2 and the consequent downregulation of \u03b2-catenin. Interestingly, pretreatment with jorunnamycin A at 0.5 \u03bcM for 24 h considerably sensitized lung CSCs to cisplatin-induced apoptosis, as evidenced by upregulated p53 and decreased Bcl-2 in jorunnamycin A-pretreated CSC-enriched spheroids. Moreover, the combination treatment of jorunnamycin A (0.5 \u03bcM) and cisplatin (25 \u03bcM) also diminished CD133-overexpresssing cells presented in CSC-enriched spheroids. Thus, evidence on the regulatory functions of jorunnamycin A may facilitate the development of this marine-derived compound as a novel chemotherapy agent that targets CSCs in lung cancer treatment.<\/jats:p>","DOI":"10.3390\/md19050261","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T22:51:42Z","timestamp":1620255102000},"page":"261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Jorunnamycin A Suppresses Stem-Like Phenotypes and Sensitizes Cisplatin-Induced Apoptosis in Cancer Stem-Like Cell-Enriched Spheroids of Human Lung Cancer Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Somruethai","family":"Sumkhemthong","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8941-1046","authenticated-orcid":false,"given":"Supakarn","family":"Chamni","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Natural Products and Nanoparticles Research Unit (NP2), Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5705-1376","authenticated-orcid":false,"given":"Gea U.","family":"Ecoy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Pharmacy, School of Health Care Professions, University of San Carlos, Cebu 6000, Philippines"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pornchanok","family":"Taweecheep","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khanit","family":"Suwanborirux","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Natural Products and Nanoparticles Research Unit (NP2), Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eakachai","family":"Prompetchara","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3103-3249","authenticated-orcid":false,"given":"Pithi","family":"Chanvorachote","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Cell-Based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-192X","authenticated-orcid":false,"given":"Chatchai","family":"Chaotham","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Cell-Based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J. 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