20(S)-Ginsenoside Rh2 Induce the Apoptosis and Autophagy in U937 and K562 Cells

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.

Increased antitumor efficacy of ginsenoside Rh 2 via mixed micelles: in vivo and in vitro evaluation

“…However, due to the poor solubility of Rh 2 , its clinical application is restricted. In recent years, researchers have developed a variety of nano pharmaceuticals to improve the solubility of Rh 2 , such as self-microemulsions (Yang et al., 2017 ), nanoparticles (Singh et al., 2017 ; Kim et al., 2019 ), liposome-based delivery systems (Yang et al., 2016 ), and pH-sensitive mixed micelles (Zhuang et al., 2018 ).…”

“…Studies show that Rh 2 can inhibit melanoma (Wang et al., 2017 ), glioma (Kim et al., 2007 ), liver cancer (Yang et al., 2016 ), breast cancer (Zare-Zardini et al., 2018 ), and lung cancer (An et al., 2013 ). Rh2 inhibits tumor tissue growth by inhibiting the proliferation of tumor cells, inducing apoptosis (Zhuang et al., 2018 ), inhibiting tumor invasion (Li et al., 2015 ), migration and angiogenesis (Chen et al., 2018 ), and reversing/delaying multidrug resistance (Wen et al., 2015 ). The growth of tumor cells was interfered by regulating tumor microenvironment.…”

Diverse autophagy and apoptosis in myeloid leukemia cells induced by 20(s)-GRh2 and blue LED irradiation

“…Accordingly, understanding the effect of autophagy on apoptosis is of great signicance as it can make treatment more effective. 2,29,[34][35][36] In this study, we investigated the difference of autophagy induced by BL, GRh2 and BL-GRh2 in myeloid leukemia cells. We observed a complex inuence of autophagy on apoptosis induced by 20(S)-GRh2, BL, and BL-GRh2 therapy.…”

“…28 Our previous study also demonstrated that 20(S)-GRh2 can induce autophagy which has a cooperative manner with apoptosis in U937 and K562 cells. 29 In this study, we demonstrated that autophagy induced by traditional Chinese medicine (20(s)-GRh2) alone or combined with physical factor (BL) has different impacts on apoptosis in AML and CML leukemic cells. Autophagy and apoptosis induced by combined BL-GRh2 treatment and BL alone indicated mutually reinforcing effects.…”

Ginsenoside Rh2 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury by Regulating the TLR4/PI3K/Akt/mTOR, Raf-1/MEK/ERK, and Keap1/Nrf2/HO-1 Signaling Pathways in Mice

“…The main active constituents of ginseng (the root of Panax ginseng Meyer; Korean ginseng) are ginsenosides that are receiving considerable attention in the field of traditional medicine due to their potential beneficial properties on human health, including anti-inflammatory, antioxidant, antidiabetic, antitumor, immunological regulation, and slowing the aging process [ 9 , 10 ] properties.…”