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

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.