Effect of dehydrocostus lactone on the proliferation of chronic myeloid leukemia K562 cells and its mechanism

Abstract

Objective To explore the effect of dehydrocostus lactone on the proliferation of chronic myeloid leukemia cell line K562 and its mechanism. Methods K562 cells in logarithmic growth phase were treated with different concentrations of dehydrocostus lactone. Cell morphology was observed by Wright-Giemsa staining. Cell proliferation was detected by CCK-8 method. Cell cycle, apoptosis and the expressions of cell surface differentiation antigen CD14 and CD11b were detected by flow cytometry. JAK-STAT pathway and the expressions of apoptosis and cell cycle related proteins were detected by Western blot. Results Compared with the control group, the proliferation of K562 cells could be inhibited after treatment with different concentrations (4.0, 6.0, 8.0, 10.0 and 12.0 μmol/L) of dehydrocostus lactone for 24 h, and the difference was statistically significant (F = 109.510, P < 0.05). After treatment with 5.0 and 10.0 μmol/L dehydrocostus lactone for 24 h, the apoptosis rates of K562 cells were (16.1±3.8)% and (29.6±4.3)%, which were higher than that of the control group [(3.1±0.5)%] (F = 83.255, P < 0.05). After treatment with 5.0 and 10.0 μmol/L dehydrocostus lactone for 24 h, the proportion of G2/M phase cells in K562 cells were (17.0±3.2)% and (28.8±3.9)%, which were higher than that of the control group [(9.1±2.3)%] (F = 161.598, P < 0.05); the proportion of S phase cells in K562 cells were (48.1±3.9)% and (61.0±5.4)%, which were higher than that of the control group [(39.6±3.6)%] (F = 192.356, P < 0.05). After treatment with 2.5 and 5.0 μmol/L dehydrocostus lactone for 72 h, the expression rates of CD14 in K562 cells were (28.6±3.9)% and (41.1±4.4)%, which were higher than that in the control group [(3.1±0.5)%] (F = 132.811, P < 0.05); the expression rates of CD11b in K562 cells were (42.4±5.0)% and (61.2±5.7)%, which were higher than that in the control group [(4.2±1.1)%] (F = 179.553, P < 0.05). Dehydrocostus lactone could decrease the expressions of JAK2, STAT5, cyclin E, CDK2, cyclin A, CDC25C, cyclin B1, CDK1 and bcl-2 proteins, and up-regulate the expressions of p21 and bax proteins. Conclusion Dehydrocostus lactone can inhibit the proliferation of chronic myeloid leukemia K562 cells, which may be achieved by cell cycle arrest, induction of apoptosis and differentiation. Key words: Dehydrocostus lactone; Cell cycle; Apoptosis; Differentiation; Leukemia