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Article

The Anti-Tumor and Bortezomib-Sensitizing Effects of Apigenin in Multiple Myeloma

School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Curr. Issues Mol. Biol. 2025, 47(9), 717; https://doi.org/10.3390/cimb47090717
Submission received: 27 June 2025 / Revised: 26 August 2025 / Accepted: 2 September 2025 / Published: 3 September 2025
(This article belongs to the Section Molecular Pharmacology)

Abstract

Multiple myeloma (MM) is a kind of plasma cell neoplasm, accounting for approximately 10% of hematologic malignancies, with a high mortality rate. Apigenin (APG), a flavonoid, has been reported to have antiviral, antibacterial, antioxidant, and anticancer properties. However, the impact of APG on MM and bortezomib (BTZ) sensitization has not been investigated. The effects of APG on the proliferation, cell cycle, apoptosis, and oxidative stress of RPMI-8226 and U266 cells were investigated using CCK-8 assay, crystal violet staining, flow cytometry, Western blot, and PCR. It was observed that APG treatment increased the G1 phase cells, by which the expression of P21 increased, and the expression of CDK2 and Cyclin D1 decreased. Even though Necrostatin-1 (a potent necroptosis inhibitor) and Fer-1 (a ferroptosis inhibitor) could attenuate the effect of APG, the effect of Z-VAD-FMK (a pan-caspase inhibitor) was more significant. APG treatment increased the transcription of P53 and BAX, and the level of cleaved-PARP1 and cleaved-Caspase 3 in two MM cell strains. In addition, the APG application could dose-dependently increase the ROS, MDA, and GSSH levels, and decrease the GSH level in both cell strains, by which the transcription of GCLC, NQO1, GSTM2, NRF2, and GPX4 were attenuated. Finally, APG enhances the inhibitory effect of BTZ on MM cell growth. This study provides a potential therapeutic approach of APG on MM.
Keywords: apigenin; multiple myeloma; oxidative stress; apoptosis; bortezomib apigenin; multiple myeloma; oxidative stress; apoptosis; bortezomib

Share and Cite

MDPI and ACS Style

Chen, Y.; Wu, L.; Wang, S.; Chen, H.; Chen, M.; Huang, Y.; Ding, B. The Anti-Tumor and Bortezomib-Sensitizing Effects of Apigenin in Multiple Myeloma. Curr. Issues Mol. Biol. 2025, 47, 717. https://doi.org/10.3390/cimb47090717

AMA Style

Chen Y, Wu L, Wang S, Chen H, Chen M, Huang Y, Ding B. The Anti-Tumor and Bortezomib-Sensitizing Effects of Apigenin in Multiple Myeloma. Current Issues in Molecular Biology. 2025; 47(9):717. https://doi.org/10.3390/cimb47090717

Chicago/Turabian Style

Chen, Ye, Lan Wu, Siyu Wang, Huihao Chen, Miaojun Chen, Yanfen Huang, and Bin Ding. 2025. "The Anti-Tumor and Bortezomib-Sensitizing Effects of Apigenin in Multiple Myeloma" Current Issues in Molecular Biology 47, no. 9: 717. https://doi.org/10.3390/cimb47090717

APA Style

Chen, Y., Wu, L., Wang, S., Chen, H., Chen, M., Huang, Y., & Ding, B. (2025). The Anti-Tumor and Bortezomib-Sensitizing Effects of Apigenin in Multiple Myeloma. Current Issues in Molecular Biology, 47(9), 717. https://doi.org/10.3390/cimb47090717

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