1. 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
- Author
-
Chia Yu Ma, Jai Sing Yang, Tung Yuan Lai, Hui Ying Hsu, Rick Sai-Chuen Wu, W. Gibson Wood, Kung Wen Lu, Jing Gung Chung, Jen Jyh Lin, Po-Yuan Chen, and King Chuen Wu
- Subjects
Cell cycle checkpoint ,Cell Survival ,Cell ,Pharmaceutical Science ,Antineoplastic Agents ,Apoptosis ,DNA Fragmentation ,Biology ,Mice ,In vivo ,Cell Line, Tumor ,Drug Discovery ,medicine ,Animals ,Humans ,Viability assay ,Membrane Potential, Mitochondrial ,Pharmacology ,Leukemia, Experimental ,Plant Extracts ,Myeloid leukemia ,Cell Cycle Checkpoints ,Xenograft Model Antitumor Assays ,Molecular biology ,Gynostemma ,Cell biology ,medicine.anatomical_structure ,Complementary and alternative medicine ,Cell culture ,Caspases ,Molecular Medicine ,DNA fragmentation ,Calcium ,Reactive Oxygen Species ,Transcription Factor CHOP ,DNA Damage ,Phytotherapy ,Transcription Factors - 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 Ca(2+) 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 Ca(2+) 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.
- Published
- 2011
- Full Text
- View/download PDF