Chaga Mushroom Triterpenoids Inhibit Dihydrofolate Reductase and Act Synergistically with Conventional Therapies in Breast Cancer.

Autor: Wang J; School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy., Beghelli D; School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy., Amici A; School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy., Sut S; DAFNAE Dipartimento di Agronomia, Animali, Alimenti, Risorse Naturali e Ambiente, University of Padova, 35020 Legnaro, Italy., Dall'Acqua S; DSF Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35121 Padova, Italy., Lupidi G; School of Pharmacy, University of Camerino, 62032 Camerino, Italy., Dal Ben D; School of Pharmacy-Chemistry Interdisciplinary Project (CHIP), University of Camerino, 62032 Camerino, Italy., Bistoni O; Rheumatology Unit, Department of Medicine and Surgery, University of Perugia, 06123 Perugia, Italy., Tomassoni D; School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy., Belletti B; Molecular Oncology Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy., Musa S; Natural Compounds and Organic Synthesis, Migal-Galilee Research Institute, Kiryat Shmona 11016, Israel.; Department of Biotechnology, Tel Hai College, Kiryat Shmona 1220800, Israel., Mahajna J; Natural Compounds and Organic Synthesis, Migal-Galilee Research Institute, Kiryat Shmona 11016, Israel.; Cancer Drug Discovery Program, Migal, Galilee Research Institute, P.O. Box 831, Kiryat Shmona 11016, Israel., Pucciarelli S; School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy., Marchini C; School of Biosciences and Veterinary Medicine, Via Gentile III da Varano, University of Camerino, 62032 Camerino, Italy.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2024 Nov 17; Vol. 14 (11). Date of Electronic Publication: 2024 Nov 17.
DOI: 10.3390/biom14111454
Abstrakt: Inonotus obliquus (Chaga) is a medicinal mushroom with several pharmacological properties that is used as a tea in traditional Chinese medicine. In this study, Chaga water extract was digested in vitro to mimic the natural processing and absorption of its biocomponents when it is consumed as functional beverage, and its anticancer activities were evaluated in breast cancer (BC) cell lines, representing HER2-positive and triple-negative subtypes. After chemical characterization by liquid chromatography/mass spectrometry (HR-QTOF) analysis, the effect of Chaga biocomponents on cell viability and cell cycle progression was assessed by MTT assay, FACS analysis, and Western blot. Dihydrofolate reductase (DHFR) activity was measured by an enzymatic assay. Four highly bioactive triterpenoids (inotodiol, trametenolic acid, 3-hydroxy-lanosta-8,24-dien-21-al, and betulin) were identified as the main components, able to decrease BC cell viability and block the cell cycle in G0/G1 by inducing the downregulation of cyclin D1, CDK4, cyclin E, and phosphorylated retinoblastoma protein. DHFR was identified as their crucial target. Moreover, bioactive Chaga components exerted a synergistic action with cisplatin and with trastuzumab in SK-BR-3 cells by inhibiting both HER2 and HER1 activation and displayed an immunomodulatory effect. Thus, Inonotus obliquus represents a source of triterpenoids that are effective against aggressive BC subtypes and display properties of targeted drugs.
Competing Interests: The authors declare no conflicts of interest.
Databáze: MEDLINE
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