Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Exp Med. Jun 20, 2025; 15(2): 102897
Published online Jun 20, 2025. doi: 10.5493/wjem.v15.i2.102897
Diarylpentanoid, a curcumin analog, inhibits malignant meningioma growth in both in vitro and in vivo models
Anna Terasawa, Kazuhiro Shimazu, Hiroshi Nanjo, Masatomo Miura, Hiroyuki Shibata
Anna Terasawa, Department of Clinical Oncology, Akita University, Akita 010-8543, Japan
Kazuhiro Shimazu, Hiroyuki Shibata, Department of Clinical Oncology, Akita University Graduate School of Medicine, Akita 010-8543, Japan
Hiroshi Nanjo, Department of Pathology, Akita University, Akita 010-8543, Japan
Masatomo Miura, Department of Pharmacokinetics, Graduate School of Medicine, Akita University, Akita, Japan
Author contributions: Terasawa A, Shimazu K, Shibata H designed and coordinated the study; Terasawa A, Shimazu K, Shibata H, Miura M, Shibata H performed the experiments, acquired and analyzed data; Terasawa A, Shimazu K, Nanjo H, Miura M, Shibata H interpreted the data; Terasawa A, Shibata H wrote the manuscript; all authors approved the final version of the article.
Supported by TAIHO Pharmaceutical, No. AS2023A000122715; and Nippon Kayaku, No. NKCS20230416001.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Akita University.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals. This study proposal received approval from the Research Ethics Committee at Akita University: No. b-1-0440.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hiroyuki Shibata, MD, PhD, Professor, Department of Clinical Oncology, Akita University Graduate School of Medicine, Hondo 1-1-1, Akita 010-8543, Japan. hiroyuki@med.akita-u.ac.jp
Received: November 1, 2024
Revised: December 31, 2024
Accepted: January 21, 2025
Published online: June 20, 2025
Processing time: 166 Days and 7.5 Hours
Abstract
BACKGROUND

Malignant meningioma metastasizes systemically, primarily due to its role in epithelial-mesenchymal transition. Although the prognosis is extremely poor, drug development efforts have been limited, because this tumor is categorized as a rare form.

AIM

To examine growth suppressive effect of GO-Y030, a diarylpentanoid curcumin analog, (1E,4E)-1,5-bis [3,5-bis (methoxymethoxy) phenyl] penta-1,4-dien-3-one against the malignant meningioma.

METHODS

The growth suppression of malignant meningioma cells by GO-Y022 and GO-Y030 were examined, using IOMM-Lee and HKBMM cell lines. Male nude mice aged eight weeks, specifically BALB/cSlc-nu/nu mice received a subcutaneous inoculation of IOMM-Lee (107 cells/site) on their back and 30 μg/kg of recombinant hepatocellular growth factor (HGF) was injected into the tumor every three days. After confirmed the growth tumor mass, 500 μL of GO-Y030 diluted with PBS were administrated intraperitoneally daily at doses of 1 mg/kg and 2 mg/kg, respectively.

RESULTS

GO-Y030 exhibits a growth inhibitory effect on malignant meningioma cell lines, IOMM-Lee and HKBMM ranging from 0.8-2.0 μM in vitro. Notably, GO-Y030’s inhibitory effect is about 10 to 16th times more potent than that of curcumin, which has previously demonstrated potential in combating malignant meningioma. In mouse models, the intraperitoneal administration of GO-Y030 effectively suppresses the growth of malignant meningioma tumors that have been inoculated in the back (P = 0.002). High-performance liquid chromatography analysis has confirmed the distribution of GO-Y030 in the bloodstream and brain tissue. Moreover, GO-Y030 demonstrates the ability to significantly suppress HGF (P < 0.01), nuclear factor kappa B (P < 0.001), and N-cadherin (P < 0.001), all of which contribute to the epithelial-mesenchymal transition.

CONCLUSION

GO-Y030 holds promise as a potent compound for the systemic inhibition of malignant meningioma. GO-Y030 has higher tumor growth inhibitory effect against meningiomas than curcumin, which is known to have antitumor activity through multi-molecular target control resulting in apoptosis induction. GO-Y030 controls at least three molecules of HGF, nuclear factor kappa B, and N-cadherin.

Keywords: Malignant meningioma; Curcumin; Diarylpentanoid curcumin analog; Hepatocellular growth factor; Nuclear factor kappa B; N-cadherin

Core Tip: Malignant meningiomas have a poor prognosis, but drug development is limited due to their rarity. The curcumin analog GO-Y030 showed approximately 10-16 times stronger inhibitory effects than curcumin on IOMM-Lee and HKBMM cell lines, in vitro. Intraperitoneal administration of GO-Y030 also significantly inhibited the growth of malignant meningiomas, IOMM-Lee inoculated in nude mouse models. GO-Y030 significantly inhibited hepatocyte growth factor, nuclear factor kappa B, and N-cadherin, which contribute to epithelial-mesenchymal transition.