Senescence as A Consequence of Ginsenoside Rg1 Response on K562 Human Leukemia Cell Line

Abstract

Aims and <b>Background:</b> Traditional chemotherapy strategies for human leukemia commonly use drugs basedon cytotoxicity to eradicate cancer cells. One predicament is that substantial damage to normal tissues is likelyto occur in the course of standard treatments. Obviously, it is urgent to explore therapies that can effectivelyeliminate 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. <br/><b>Methods</b>: In the current study, humanleukemia K562 cells were subjected to Rg1 exposure. The optimal drug concentration and duration with K562cells was obtained by MTT colorimetric test. Effects of Rg1 on cell cycle were analyzed using flow cytometry andby SA-β-Gal staining. Colony-forming ability was measured by colony-assay. Telomere lengths were assessedby Southern blotting and expression of senescence-associated proteins P21, P16 and RB by Western blotting.Ultrastructural morphology changes were observed by transmission electron microscopy. <br/><b>Results</b>: K562 cellsdemonstrated a maximum proliferation inhibition rate with an Rg1 concentration of 20 μ mol·L-1 for 48h, thecells exhibiting dramatic morphological alterations including an enlarged and flat cellular morphology, largermitochondria and increased number of lysosomes. Senescence associated-β-galactosidase (SA-β-Gal) activitywas increased. K562 cells also had decreased ability for colony formation, and shortened telomere length as wellas reduction of proliferating potential and arrestin G2/M phase after Rg1 interaction. The senescence associatedproteins P21, P16 and RB were significantly up-regulated. <br/><b>Conclusion</b>: Ginsenoside Rg1 can induce a state ofsenescence in human leukemia K562 cells, which is associated with p21-Rb and p16-Rb pathways.