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Abstract Title:

[Downregulation of MCL-1 by Diallyl Disulfide Induces G/M Arrest in Human Leukemia K562 Cells and Its Mechanism].

Abstract Source:

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Jun ;26(3):750-755. PMID: 29950215

Abstract Author(s):

Xiao-Xia Ji, Fang Liu, Hong Xia, Jie He, Hui Tan, Lan Yi, Qi Su

Article Affiliation:

Xiao-Xia Ji

Abstract:

OBJECTIVE: To investigate the inducing effect of down-regulation of MCL-1 by diallyl disulfide(DADS) on the G/M arrest of human leukemia K562 cells and its mechanisms.

METHODS: CCK-8 was used to detect the effect of DADS on proliferation of K562 cells, flow cytometry was employed to observe the effect of cycle arrest by DADS and RNAi silencing MCL-1 gene in K562 cells. The expressions of MCL-1, PCNA and CDK1 in K562 cells treated with DADS were detected by Western blot. The amphigamy of MCL-1 with PCNA and CDK1 was detected by Coimmunoprecipitation.

RESULTS: CCK-8 detection showed that the inhibition rates of K562 cells treated with 15, 30, 60, 120, 240µmol/L DADS were 32.48%, 59.34%, 66.42%, 77.06%, 81.05% respectively (P<0.05). Flow cytometry analysis revealed that the perecentages of G/M cells were increased to 18.6% and 34.4%, 17.5% and 28.5%, respectively at 24 and 48 h after treating K562 cells with 60 and 120µmol/L DADS (P<0.05). And the perecentage of G/M cells of silencing MCL-1 was significantly increased (P<0.05). Silencing effects of MCL-1+DADS on the cells were enhanced more significantly as compared with DADS or MCL-1 alone (P<0.05). Western blot exhibited that DADS could markedly downregulate the expression of MCL-1, PCNA and CDK1(P<0.05). Coimmunoprecipitation revealed that MCL-1 bound with PCNA and CDK1, then forming heterodimers, which were downregulated respectively more significantly than that in the control group after treating K562 cells with DADS for 8 h (P<0.05).

CONCLUSION: DADS can inhibit the K562 cell proliferation and induce them arrest G/M through downregulation of MCL-1, then decreasing the expression of PCNA and CDK1 in hunan leukemia K562 cells. Moreover, silencing MCL-1 can enhance the effect of DADS.

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Sayer Ji
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