Journal article
A Bibenzyl from Dendrobium pachyglossum Exhibits Potent Anti-Cancer Activity Against Glioblastoma Multiforme
Antioxidants, Vol.14(10), 1212
10/07/2025
DOI: 10.3390/antiox14101212
PMCID: PMC12561214
PMID: 41154521
Abstract
Glioblastoma multiforme (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Natural phytochemicals from Dendrobium species, particularly bibenzyl derivatives, possess diverse pharmacological activities, yet their potential against GBM remains largely unexplored. Here, we investigated the anticancer activity of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a potent antioxidant bibenzyl derivative isolated from Dendrobium pachyglossum. In U87MG cells, TDB reduced viability in a dose- and time-dependent manner, suppressed clonogenic growth, induced apoptosis via Bax upregulation and Bcl-xL/Mcl-1 downregulation, and inhibited both mTORC1 and mTORC2 signaling. TDB also impaired cell migration and downregulated epithelial–mesenchymal transition (EMT)-associated proteins. Notably, TDB enhanced the cytotoxicity of temozolomide (TMZ), the current standard of care for GBM. These TMZ-sensitizing properties were further confirmed in patient-derived xenograft (PDX) Jx22 cells. To assess its potential for central nervous system delivery, blood–brain barrier (BBB) permeability was predicted using four independent in silico platforms—ADMETlab 3.0, LogBB_Pred, LightBBB, and BBB Predictor (Tree2C)—all of which consistently classified TDB as BBB-permeable. This predicted CNS accessibility, together with its potent anticancer profile, underscores TDB’s translational promise. Collectively, our findings identify TDB as a plant-derived antioxidant with multifaceted anti-GBM activity and favorable BBB penetration potential, warranting further in vivo validation and preclinical development as a novel therapeutic candidate for GBM.
Details
- Title: Subtitle
- A Bibenzyl from Dendrobium pachyglossum Exhibits Potent Anti-Cancer Activity Against Glioblastoma Multiforme
- Creators
- Hnin Mon Aung - Chulalongkorn UniversityOnsurang Wattanathamsan - Chulalongkorn UniversityKittipong Sanookpan - Chulalongkorn UniversityAphinan Hongprasit - Chulalongkorn UniversityChawanphat Muangnoi - Mahidol UniversityRianthong Phumsuay - Mahidol UniversityThanawan Rojpitikul - Chulalongkorn UniversityBoonchoo Sritularak - Chulalongkorn UniversityTankun Bunlue - Chulalongkorn UniversityNaphat Chantaravisoot - Chulalongkorn UniversityClaudia R. Oliva - University of IowaCorinne E. Griguer - University of IowaVisarut Buranasudja - Chulalongkorn University
- Resource Type
- Journal article
- Publication Details
- Antioxidants, Vol.14(10), 1212
- DOI
- 10.3390/antiox14101212
- PMID
- 41154521
- PMCID
- PMC12561214
- NLM abbreviation
- Antioxidants (Basel)
- ISSN
- 2076-3921
- eISSN
- 2076-3921
- Publisher
- MDPI
- Grant note
- National Research Council of Thailand (NRCT) and Chulalongkorn University: N42A680085 Second Century Fund (C2F), Chulalongkorn Universitythe Faculty of Pharmaceutical Sciences, Chulalongkorn University
This research was supported by the Second Century Fund (C2F), Chulalongkorn University, and by the Faculty of Pharmaceutical Sciences, Chulalongkorn University. Additional financial support was provided through the National Research Council of Thailand (NRCT) and Chulalongkorn University (N42A680085).
- Language
- English
- Date published
- 10/07/2025
- Academic Unit
- Radiation Oncology
- Record Identifier
- 9985014899202771
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