Antiproliferative activities of panduratin A and its derivatives against U-251 MG glioblastoma cells and U-251 MG cancer stem-like cells: structure–activity relationships and identification of PHB2 as a candidate binding protein
- 1Laboratory of Pharmacognosy, Kyoto Pharmaceutical University, 1, Misasagi-Shichono-cho, Yamashina-ku, Kyoto-shi, Kyoto, 607-8412 Japan
- 2Laboratory of Clinical and Translational Physiology, Kyoto Pharmaceutical University, 5, Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto-shi, Kyoto, 607-8414 Japan
Abstract
Panduratin A (1), a cyclohexenyl chalcone isolated from Boesenbergia rotunda, has been reported to exhibit various biological activities, including antitumor effects. However, its antiproliferative activity against glioblastoma cells and glioblastoma-derived cancer stem-like cells (CSCs), and the molecular basis of this activity, remain incompletely elucidated. In this study, we evaluated the antiproliferative activity of 1 against U-251 MG glioblastoma cells (non-CSCs) and U-251 MG CSCs and found that 1 exhibited potent activity against both cell populations. To investigate the structural features associated with this activity, cyclohexenyl chalcone derivatives of 1 (2–11) were synthesized through a chalcone intermediate generated from an acetophenone precursor, followed by Diels–Alder reactions with dienes. Structure–activity relationship analysis, particularly in U-251 MG non-CSCs, suggested that the phenolic oxygen functionalities of 1 contribute to its potent activity, whereas some acetylated derivatives retained moderate activity. Based on this observation, affinity-based target identification using U-251 MG non-CSC extracts identified prohibitin 2 (PHB2), an inner mitochondrial membrane protein, as a candidate binding protein for 1. In these cells, 1 also markedly altered the mitochondrial morphology and reduced the mitochondrial membrane potential. Together, these findings suggest that the antiproliferative activity of 1 in U-251 MG glioblastoma cells may be associated with PHB2 and mitochondrial alterations.
Graphical Abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11418-026-02095-6.
Related
- Fragment‐Linked Purine Derivatives as Inhibitors of (p)ppGpp Synthetases: Design, Synthesis, and Structure‐Activity Relationships
- Identification of Survival-Associated miRNA Signatures in Glioblastoma Using Next-Generation Sequencing
- Design, Amino-Acid-Derived Analogues of FTY-720 and OSU-2S as PP2A Activators: Structure-Activity Relationships and Identification of Lead Compound XML-3D
- Discovery of natural flavanones as potential PRMT4 inhibitors with antiproliferative activity against colorectal cancer cells
- Butyrate-associated antiproliferative and antitumor effects of Eubacterium limosum KGMB01548 in colorectal cancer
BibTeX
@article{araki2026antiproliferative,
title = {{Antiproliferative activities of panduratin A and its derivatives against U-251 MG glioblastoma cells and U-251 MG cancer stem-like cells: structure–activity relationships and identification of PHB2 as a candidate binding protein}},
author = {Kousuke Araki and Yuna Yoshitani and Rina Okamoto and Shigekuni Hosogi and Ryota Fujikawa and Moe Kaneko and Reia Ishikura and Chiho Shimadzu and Yuzuki Takahashi and Rina Mantani and Tomoe Ohta and Seikou Nakamura},
journal = {Journal of Natural Medicines},
year = {2026},
month = oct,
doi = {10.1007/s11418-026-02095-6},
url = {https://doi.org/10.1007/s11418-026-02095-6},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Antiproliferative activities of panduratin A and its derivatives against U-251 MG glioblastoma cells and U-251 MG cancer stem-like cells: structure–activity relationships and identification of PHB2 as a candidate binding protein
AU - Kousuke Araki
AU - Yuna Yoshitani
AU - Rina Okamoto
AU - Shigekuni Hosogi
AU - Ryota Fujikawa
AU - Moe Kaneko
AU - Reia Ishikura
AU - Chiho Shimadzu
AU - Yuzuki Takahashi
AU - Rina Mantani
AU - Tomoe Ohta
AU - Seikou Nakamura
PY - 2026
DA - 2026/10/13
JO - Journal of Natural Medicines
DO - 10.1007/s11418-026-02095-6
UR - https://doi.org/10.1007/s11418-026-02095-6
AB - Panduratin A (1), a cyclohexenyl chalcone isolated from Boesenbergia rotunda, has been reported to exhibit various biological activities, including antitumor effects. However, its antiproliferative activity against glioblastoma cells and glioblastoma-derived cancer stem-like cells (CSCs), and the molecular basis of this activity, remain incompletely elucidated. In this study, we evaluated the antiproliferative activity of 1 against U-251 MG glioblastoma cells (non-CSCs) and U-251 MG CSCs and found that 1 exhibited potent activity against both cell populations. To investigate the structural features associated with this activity, cyclohexenyl chalcone derivatives of 1 (2–11) were synthesized through a chalcone intermediate generated from an acetophenone precursor, followed by Diels–Alder reactions with dienes. Structure–activity relationship analysis, particularly in U-251 MG non-CSCs, suggested that the phenolic oxygen functionalities of 1 contribute to its potent activity, whereas some acetylated derivatives retained moderate activity. Based on this observation, affinity-based target identification using U-251 MG non-CSC extracts identified prohibitin 2 (PHB2), an inner mitochondrial membrane protein, as a candidate binding protein for 1. In these cells, 1 also markedly altered the mitochondrial morphology and reduced the mitochondrial membrane potential. Together, these findings suggest that the antiproliferative activity of 1 in U-251 MG glioblastoma cells may be associated with PHB2 and mitochondrial alterations. Graphical Abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11418-026-02095-6.
SN - 1340-3443
SN - 1861-0293
ER -