Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70

Zhang, Miaomiao; Wang, Jinfeng; Jiang, Rongsong; Liu, Ming; Zhang, Weiyi

doi:10.3390/molecules30112294

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Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70

by

Miaomiao Zhang

^1,†,

Jinfeng Wang

¹,

Rongsong Jiang

¹,

Ming Liu

^1,2 and

Weiyi Zhang

^{1,3,4,5,*,†}

¹

School of Pharmacy, Xinjiang Medical University, Urumchi 830017, China

²

Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China

³

Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Urumchi 830017, China

⁴

Xinjiang Key Laboratory of Biopharmaceuticals and Medical Devices, Urumchi 830017, China

⁵

Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, Urumchi 830017, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Molecules 2025, 30(11), 2294; https://doi.org/10.3390/molecules30112294

Submission received: 21 April 2025 / Revised: 19 May 2025 / Accepted: 22 May 2025 / Published: 23 May 2025

(This article belongs to the Special Issue Recent Advances in Development of Small Molecules to Fight Cancer—2nd Edition)

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Abstract

Leukemia is a malignant tumor of the hematopoietic system. Approximately 15% of adult leukemias are chronic myeloid leukemias (CMLs), and this incidence increases annually. The BCR-ABL oncoprotein drives the initiation, promotion, and progression of CML. Although tyrosine kinase inhibitors (TKIs) are first-line therapies for CML, BCR-ABL-mediated drug resistance limits their clinical efficacy and patient prognosis. Perillaldehyde (PAE), a monoterpene and primary volatile oil from perilla, is a promising small-molecule candidate for degrading BCR-ABL and has potential medical applications. The molecular mechanism showed that PAE regulated the expression of autophagy- and apoptosis-related proteins in K562 cells. Confocal laser observation showed that PAE damaged the mitochondrial membrane potential and induced ROS generation. Further evaluations indicated that PAE targeted HSP70 and inactivated the phosphorylation of BCR-ABL, thereby inhibiting its downstream proteins. This study may produce a lead compound for CML therapy as PAE may be an effective treatment for further exploration.

Keywords: perillaldehyde; chronic myeloid leukemia; apoptosis; autophagy; HSP70

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MDPI and ACS Style

Zhang, M.; Wang, J.; Jiang, R.; Liu, M.; Zhang, W. Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70. Molecules 2025, 30, 2294. https://doi.org/10.3390/molecules30112294

AMA Style

Zhang M, Wang J, Jiang R, Liu M, Zhang W. Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70. Molecules. 2025; 30(11):2294. https://doi.org/10.3390/molecules30112294

Chicago/Turabian Style

Zhang, Miaomiao, Jinfeng Wang, Rongsong Jiang, Ming Liu, and Weiyi Zhang. 2025. "Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70" Molecules 30, no. 11: 2294. https://doi.org/10.3390/molecules30112294

APA Style

Zhang, M., Wang, J., Jiang, R., Liu, M., & Zhang, W. (2025). Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70. Molecules, 30(11), 2294. https://doi.org/10.3390/molecules30112294

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Unlocking the Potential of Perillaldehyde: A Novel Mechanism for Chronic Myeloid Leukemia by Targeting HSP70

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