1. Jorunnamycin A Suppresses Stem-Like Phenotypes and Sensitizes Cisplatin-Induced Apoptosis in Cancer Stem-Like Cell-Enriched Spheroids of Human Lung Cancer Cells.
- Author
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Sumkhemthong S, Chamni S, Ecoy GU, Taweecheep P, Suwanborirux K, Prompetchara E, Chanvorachote P, and Chaotham C
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Cisplatin pharmacology, Down-Regulation drug effects, Drug Synergism, Humans, Isoquinolines chemistry, Isoquinolines isolation & purification, Lung Neoplasms drug therapy, Nanog Homeobox Protein genetics, Nanog Homeobox Protein metabolism, Octamer Transcription Factor-3 genetics, Octamer Transcription Factor-3 metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Quinolones chemistry, Quinolones isolation & purification, SOXB1 Transcription Factors genetics, SOXB1 Transcription Factors metabolism, Transcription Factors genetics, Transcription Factors metabolism, Tumor Suppressor Protein p53 metabolism, Xestospongia chemistry, Apoptosis drug effects, Isoquinolines pharmacology, Lung Neoplasms pathology, Neoplastic Stem Cells drug effects, Quinolones pharmacology, Spheroids, Cellular drug effects
- Abstract
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.
- Published
- 2021
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