An Experimental Study on the Antileukemia Effects of Gypenosides In Vitro and In Vivo

Abstract

Purpose. Gypenosides (Gyp), found in Gynostemma pentaphyllum Makino, have been used as folk medicine for centuries and have exhibited diverse pharmacological effects, including antileukemia effects in vitro and in vivo. In the present study, Gyp were used to examine effects on cell viability, cell cycle, and induction of apoptosis in vitro. They were administered in the diet to mice injected with WEHI-3 cells in vivo. Experimental design. Effects of Gyp on WEHI-3 cells were determined by flow cytometric assay and Western blotting. Results. Gyp inhibited the growth of WEHI-3 cells. These effects were associated with the induction of G0/G1 arrest, morphological changes, DNA fragmentation, and increased sub-G1 phase. Gyp promoted the production of reactive oxygen species, increased Ca 2+ levels, and induced the depolarization of the mitochondrial membrane potential. The effects of Gyp were dose and time dependent. Moreover, Gyp increased levels of the proapoptotic protein Bax, reduced levels of the antiapoptotic proteins Bcl-2, and stimulated release of cytochrome c, AIF (apoptosis-inducing factor), and Endo G (endonuclease G) from mitochondria. The levels of GADD153, GRP78, ATF6-α, and ATF4-α were increased by Gyp, resulting in ER (endoplasmic reticular) stress in WEHI-3 cells. Oral consumption of Gyp increased the survival rate of mice injected with WEHI-3 cells used as a mouse model of leukemia. Conclusions. Results of these experiments provide new information on understanding mechanisms of Gyp-induced effects on cell cycle arrest and apoptosis in vitro and in an in vivo animal model.

Anti-Cancer Effect and the Underlying Mechanisms of Gypenosides on Human Colorectal Cancer SW-480 Cells

“…Gyp has been used as traditional Chinese herbal medicine for hundreds of years because of its variety of health benefits [20]–[22]. In the present study, Gyp induced apoptosis in human colorectal cancer SW-480 cells was investigated.…”

Anti-Cancerous Potential of Polysaccharide Fractions Extracted from Peony Seed Dreg on Various Human Cancer Cell Lines Via Cell Cycle Arrest and Apoptosis

“…seeds showed anti-tumor activities under in-vivo conditions (Atashrazm et al, 2016; Liu G. et al, 2016; Zheng et al, 2016; Wang et al, 2017). One latest review updated the anti-cancerous potential of gynostemma polysaccharide in different normal and transgenic cancer mice models (Hsu et al, 2011; Lu et al, 2012; Liu et al, 2014; Tai et al, 2016). Thus, in-vivo studies using tested polysaccharide fractions at the next level would generate their comprehensive efficacy report for better prediction of their anti-cancerous potential.…”

“…A recent review has reported the anti-cancerous mechanism of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan) GPM polysaccharides through cell cycle arrest (modulation of several cell cycle regulatory proteins (CDK-2, CDK-4, and CDK-6) (Chen et al, 2009; Cheng et al, 2011), induction of apoptosis (regulation of anti-apoptotic proteins Bcl-2, Bcl-xl and pro-apoptotic proteins Bax, Bad, and Bak (Wang et al, 2002; Hsu et al, 2011; Lin et al, 2011; Lu et al, 2012), glycolysis inhibition and immunomodulation.…”

Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca2+ release

“…Gypenosides (Gyp), saponins extracted from G. pentaphyllum , have shown a wide range of beneficial biological activities such as cholesterol-lowering, hypoglycemic, antioxidant and immune-potentiating effects [16–19]. Besides, fewer reports have described the anti-tumor activity of Gyp [20–22]. However, the specific functional component of Gyp and the detailed mechanism remain unclear.…”