Molecular evidence of anti-leukemia activity of gypenosides on human myeloid leukemia HL-60 cells in vitro and in vivo using a HL-60 cells murine xenograft model

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• 作者：Jen-Jyh  ; Lin^a ;   ; ^b ;   ; ¹ ; Hui-Ying  ; Hsu^c ;   ; ¹ ; Jai-Sing  ; Yang^d ; Kung-Wen  ; Lu^g ; Rick Sai-Chuen  ; Wu^e ; King-Chuen  ; Wu^f ; Tung-Yuan  ; Lai^g ;   ; ^h ; Po-Yuan  ; Chen^c ; Chia-Yu  ; Maⁱ ; W. Gibson  ; Wood^j ; Jing-Gung  ; Chung^c ;   ; ^k ;   ; ^{jgchung@mail.cmu.edu.tw}
• 关键词：Gypenosides ; Gynostemma pentaphyllum ; Anti-leukemia ; HL-60 cells ; Apoptosis ; In vitro ; In vivo
• 刊名：Phytomedicine
• 出版年：2011
• 出版时间：15 September 2011
• 年：2011
• 卷：18
• 期：12
• 页码：1075-1085
• 全文大小：2017 K

文摘

We have shown that gypenosides (Gyp) induced cell cycle arrest and apoptosis in many human cancer cell lines. However, there are no reports showing that show Gyp acts on human leukemia HL-60 cells in vitro and in a murine xenograft model in vivo. In the present study effects of Gyp on cell morphological changes and viability, cell cycle arrest and induction of apoptosis in vitro and effects on Gyp in an in vivo murine xenograft model. Results indicated that Gyp induced morphological changes, decreased cell viability, induced G0/G1 arrest, DNA fragmentation and apoptosis (sub-G1 phase) in HL-60 cells. Gyp increased reactive oxygen species production and Ca²⁺ levels but reduced mitochondrial membrane potential in a dose- and time-dependent manner. Gyp also changed one of the primary indicators of endoplasmic reticulum (ER) stress due to the promotion of ATF6-¦Á and ATF4-¦Á associated with Ca²⁺ release. Gyp reduced the ratio of Bcl-2 to Bax due to an increase in the pro-apoptotic protein Bax and inhibited levels of the anti-apoptotic protein Bcl-2. Oral consumption of Gyp reduced tumor size of HL-60 cell xenograft mode mice in vivo. These results provide new information on understanding mechanisms by which Gyp induces cell cycle arrest and apoptosis in vitro and in vivo.