Abstract
Acute myeloid leukemia (AML) and Chronic myelogenous leukemia (CML) are common leukemia in adults. 20(S)-GRh2 is an important bioactive substance that is present in Panax ginseng. However, there are no investigations that deal with the comparison of apoptosis, the occurrence of autophagy, and the relationship between apoptosis and autophagy after being treated with 20(S)-GRh2 in AML and CML. In this study, we explored the effect of 20(S)-GRh2 on the AML and CML (U937 and K562). Fluorescence microscopy, CCK-8, Quantitative realtime PCR, Western blot, transmission electron microscopy (TEM), and flow cytometric analysis were used to detect the occurrence of cell proliferation inhibition, apoptosis, and autophagy. By using the above methods, it was determined that apoptosis induced by 20(S)-GRh2 was more obvious in K562 than U937 cells and 20(S)-GRh2 could generate autophagy in K562 and U937 cells. When pretreated by a specific inhibitor of autophagy, (3-methyladenine), the 20(S)-GRh2-induced apoptosis was enhanced, which indicated that 20(S)-GRh2-induced autophagy may protect U937 and K562 cells from undergoing apoptotic cell death. On the other hand, pretreated by an apoptosis suppressor (Z-VAD-FMK), it greatly induced the autophagy and partially prevented 20(S)-GRh2 induced apoptosis. This phenomenon indicated that 20(S)-GRh2-induced autophagy may serve as a survival mechanism and apoptosis and autophagy could act as partners to induce cell death in a cooperative manner. These findings may provide a rationale for future clinical application by using 20(S)-GRh2 combined autophagy inhibitors for AML and CML.
Highlights
Acute myeloid leukemia (AML) and Chronic myelogenous leukemia (CML) are common leukemia malignant blood diseases [1], and an uncontrolled proliferation, different clinical manifestation, and the accumulation of deviant hematopoietic progenitor cells are the characteristics of the lethal hematological malignancy that originated from myeloid progenitor cells [2]
We firstly reported that 20(S)-Ginsenoside Rh2 (GRh2) could induce the apoptosis in the two cells and the phenomenon was more obvious in K562 than U937 cells
Our results showed a conversion from LC3-I to LC3-II and a decrease in the expression of p62 after the cells were treated by 20(S)-GRh2 (Figure 3d), which indicate that the autophagy phenomenon is increased with an increase in the dose of 20(S)-GRh2 in U937 and K562 cells
Summary
Acute myeloid leukemia (AML) and Chronic myelogenous leukemia (CML) are common leukemia malignant blood diseases [1], and an uncontrolled proliferation, different clinical manifestation, and the accumulation of deviant hematopoietic progenitor cells are the characteristics of the lethal hematological malignancy that originated from myeloid progenitor cells [2]. Liu et al reported that 20(S)-GRh2 could inhibit the proliferation of myeloid leukemia cell lines, such as K562 and KG1a, by reducing the expression and activity of HDACs, increasing the acetylation of histones, and regulating the key proteins in the downstream signaling pathways [21]. In the current investigations of related to of 20(S)-GRh2 in U937 and K562 cells, there are no studies that have been reported on the occurrence of autophagy, the comparison of apoptosis, and the relationship between apoptosis and autophagy in U937 and K562 cells induced by 20(S)-GRh2. The outcome that was obtained through our investigations provides an important basis to clarify the mechanisms underlying the activity of 20(S)-GRh2 in inhibiting the growth of U937 and K562 cells These findings provide a rationale for future clinical application by using 20(S)-GRh2 combined autophagy inhibitors for AML and CML
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