Induction of apoptosis and autophagy by dichloromethane extract from Patrinia scabiosaefolia Fisch on acute myeloid leukemia cells

Author:

Li Kejing1,Mi Leyuan12,Bai Xinyi1,Lu Yuan1,Zhang Ying3,Li Juan3ORCID,Pu Yudong4

Affiliation:

1. The First Clinical Medical College Lanzhou University Lanzhou Gansu China

2. Clinical Laboratory Center Gansu Provincial Maternity and Child‐Care Hospital (Gansu Provincial Hospital) Lanzhou Gansu China

3. Central Laboratory, The First Hospital of Lanzhou University Lanzhou University Lanzhou Gansu China

4. Precision Medicine Center of the Songshan Lake (SSL) Central Hospital of Dongguan City Dongguan Guangdong China

Abstract

AbstractPatrinia scabiosaefolia Fisch (PS), a perennial herb belonging to the genus Pinus in the family Pinnacle Sauce, has been previously known for its analgesic, anti‐inflammatory, antibacterial, and antitumor properties. However, the specific mechanism behind its antileukemic effect remains unknown. This study focused on the cytotoxicity and potential modes of action of the dichloromethane extract from PS (DEPS) in acute myeloid leukemia (AML) cells. Our results demonstrated that DEPS reduced cell viability, arrested the cell cycle in the G2/M phase, disrupted the mitochondrial membrane potential, increased reactive oxygen species (ROS) production, and upregulated the expression of Bax/Bcl‐2 and Cleaved caspase‐3. However, the impact of DEPS on cell viability and the expression of apoptosis‐associated proteins was reversed upon pretreatment with the caspase‐3 inhibitor (Z‐DEVD‐FMK) in HL‐60 cells, which demonstrated that DEPS could induce apoptosis through the mitochondria‐associated apoptotic pathway. Interestingly, DEPS also influenced autophagy by upregulating the expression of LC3II/I, P62, and Beclin‐1 proteins, and the autophagy inhibition chloroquine(CQ) could attenuate the apoptotic effects of DEPS in HL‐60 cells. Furthermore, SMART 2.0 analysis predicted that the main components present in DEPS were likely terpenoids. In conclusion, DEPS possibly exerts antileukemic effects by downregulating the PI3K/AKT and ERK pathways, thereby promoting intracellular ROS production, activating the mitochondrial apoptotic pathway, and affecting autophagy, providing valuable insights for the potential future application of PS in the treatment of AML.

Publisher

Wiley

Subject

Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine

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