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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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| Authors: | Jen-Jyh Lin Hui-Ying Hsu Jai-Sing YangKung-Wen Lu Rick Sai-Chuen WuKing-Chuen Wu Tung-Yuan Lai Po-Yuan ChenChia-Yu Ma W Gibson WoodJing-Gung Chung |
| Institution: | a Graduate Institute of Chinese Medicine, China Medical University, Taichung 404, Taiwan b Division of Cardiology, China Medical University Hospital, Taichung 404, Taiwan c Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan d Department of Pharmacology, China Medical University, 404 Taichung, Taiwan e Department of Anesthesiology, Critical Care and Pain Service, China Medical University Hospital, Taichung 404, Taiwan f Department of Anesthesiology, E-DA Hospital/I-Shou University, Kaohsiung 824, Taiwan g School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung 404, Taiwan h Department of Chinese Medicine and Internal Chinese Medicine, China Medical University Hospital 404, Taichung, Taiwan i Department of Food and Beverage Management, Technology and Science Institute of Northern Taiwan, Taipei 112, Taiwan j Department of Pharmacology, School of Medicine, Geriatric Research, Education and Clinical Center, VA Medical Center, University of Minnesota, Minneapolis, MN 55417, USA k Department of Biotechnology, Asia University, Taichung 412, Taiwan |
| Abstract: | 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-α and ATF4-α 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. |
| Keywords: | Gypenosides Gynostemma pentaphyllum Anti-leukemia HL-60 cells Apoptosis In vitro In vivo |
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