Evaluation of Apoptosis-Inducing Coumarins Isolated from Peucedanum japonicum Roots: The Potential for Leukemia Treatment via the Mitochondria-Mediated Pathway

• Published in: Cells (Basel, Switzerland) Switzerland), 2024-12, Vol.13 (23), p.1982
• Main Authors: Kang, Kyung-Yun, Ramos, Sonny C, Lee, Sung-Ju, Nam, Sang-Jip, Kim, Jong-Jin
• Format: Article
• Language: English
• Subjects: Analysis; Apiaceae - chemistry; Apoptosis; Apoptosis - drug effects; Bioactive compounds; Biological activity; Cancer; Cancer therapies; Care and treatment; caspase; Caspase-3; Cell death; Cell Line, Tumor; Chemotherapy; Column chromatography; Coumarins; Coumarins - chemistry; Coumarins - isolation & purification; Coumarins - pharmacology; Cytotoxicity; Dichloromethane; Drug therapy; Health aspects; HL-60 Cells; Humans; Laboratories; Leukemia; Leukemia - drug therapy; Leukemia - pathology; MCF-7 Cells; Medicinal plants; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial membrane potential; Natural products; NMR; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Penicillin; Penicillin G; Peucedanum; Peucedanum japonicum; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Roots - chemistry; Signal Transduction - drug effects; Spectroscopy; Tumor cell lines; Tumors
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13231982

Inducing programmed cell death in tumors is a fundamental approach in cancer therapy, prompting extensive efforts to discover bioactive compounds with anticancer properties. , a plant used in traditional medicine across East Asia, has been reported to exhibit various biological activities, including anticancer effects. This study aimed to evaluate the apoptosis-inducing effects of methanol/dichloromethane (MeOH/CH Cl ) extracts of roots and their components in HL-60 human leukemia cells. Compounds were isolated using solvent extraction and reverse-phase column chromatography, and their structures were confirmed by nuclear magnetic resonance (NMR) spectroscopy. The cytotoxicity effect of the compounds was tested on various cancer cell lines (HL-60, A549, and MCF-7). Two coumarins, (-)-isosamidin ( ) and 3'S,4'S-disenecioylkhellactone ( ), were isolated through bioactivity-guided fractionation. Compound significantly induced apoptosis in HL-60 cells, as evidenced by an increase in the sub-G1 cell population and the initiation of both early and late apoptosis. Additional apoptotic markers, including reduced mitochondrial membrane potential (MMP) and increased cleavage of caspase-3, -8, and -9, were observed. These findings suggest that compound shows potential as a candidate for leukemia treatment, providing a promising natural-product-based approach to cancer therapy.