Somruethai Sumkhemthong, Supakarn Chamni, Gea U. Ecoy, Pornchanok Taweecheep, Khanit Suwanborirux, Eakachai Prompetchara, Pithi Chanvorachote, Chatchai Chaotham
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 µM), resulted from the activation of GSK-3β and the consequent downregulation of β-catenin. Interestingly, pretreatment with jorunnamycin A at 0.5 µM 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 µM) and cisplatin (25 µM) 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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Natural Products and Nanoparticles Research Unit (NP2), Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacy, School of Health Care Professions, University of San Carlos, Cebu, 6000, Philippines; Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Center of Excellence in Vaccine Research and Development (Chula Vaccine Research Center-Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Cell-Based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand
