Senescence as A Consequence of Ginsenoside Rg1Response on K562 Human Leukemia Cell Line
Open Access
- 31 December 2012
- journal article
- Published by Asian Pacific Organization for Cancer Prevention in Asian Pacific Journal of Cancer Prevention
- Vol. 13 (12), 6191-6196
- https://doi.org/10.7314/apjcp.2012.13.12.6191
Abstract
Traditional chemotherapy strategies for human leukemia commonly use drugs based on cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likely to occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectively eliminate malignant cells without affecting normal cells. Our previous studies indicated that ginsenoside Rg1 (Rg1), a major active pharmacological ingredient of ginseng, could delay normal hematopoietic stem cell senescence. However, whether Rg1 can induce cancer cell senescence is still unclear. In the current study, human leukemia K562 cells were subjected to Rg1 exposure. The optimal drug concentration and duration with K562 cells was obtained by MTT colorimetric test. Effects of Rg1 on cell cycle were analyzed using flow cytometry and by SA-β-Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessed by Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting. Ultrastructural morphology changes were observed by transmission electron microscopy. K562 cells demonstrated a maximum proliferation inhibition rate with an Rg1 concentration of 20 μ molL-1 for 48h, the cells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, larger mitochondria and increased number of lysosomes. Senescence associated-β-galactosidase (SA-β-Gal) activity was increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as well as reduction of proliferating potential and arrestin G2/M phase after Rg1 interaction. The senescence associated proteins P21, P16 and RB were significantly up-regulated. Ginsenoside Rg1 can induce a state of senescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways.Keywords
This publication has 25 references indexed in Scilit:
- Chromatin dynamics in DNA double-strand break repairBiochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 2012
- Oncogene- and tumor suppressor gene-mediated suppression of cellular senescenceSeminars in Cancer Biology, 2011
- Anti-cancer natural products isolated from chinese medicinal herbsChinese Medicine, 2011
- Retinoblastoma‐independent regulation of cell proliferation and senescence by the p53–p21 axis in lamin A /C‐depleted cellsAging Cell, 2011
- Cellular senescence: putting the paradoxes in perspectiveCurrent Opinion in Genetics & Development, 2010
- Therapy-Induced Senescence in CancerJNCI Journal of the National Cancer Institute, 2010
- Nuclear and Chromatin Reorganization during Cell Senescence and Aging – A Mini-ReviewGerontology, 2010
- Senescence in tumours: evidence from mice and humansNature Reviews Cancer, 2010
- Hydroxyurea induces a senescence-like change of K562 human erythroleukemia cellZeitschrift für Krebsforschung und Klinische Onkologie, 2000
- Telomeres shorten during ageing of human fibroblastsNature, 1990