Induction of K562 Cell Apoptosis by As4S4 via Down-Regulating miR181

Abstract

BackgroundChronic myelogenous leukemia (CML) has unsatisfactory treatment efficacy at present. As the major component of red orpiment, tetra-arsenic tetra-sulfide (As4S4) has been recently used in treating leukemia, but with unclear mechanism targeting CML. MicroRNA (miR) is a group of endogenous non-coding RNAs regulating pathogenesis. MiR181 has been shown to exert important roles in tumor progression. The relationship between miR181 and As4S4 in inducing K562 cell apoptosis, however, is still unclear.Material/MethodsCML cell line K562 was cultured in vitro in a control group and in groups receiving various dosages (20 μM and 40 μM) of As4S4. MTT assay was employed to detect the effect on K562 cell survival. MiR181 expression was quantified by real-time PCR. MTT assay and assay kit were used to determine K562 cell survival and caspase 3 expression. Cell apoptosis was assessed by flow cytometry. Bcl-2 expression was determined by real-time PCR and Western blotting.ResultsAs4S4 significantly suppressed proliferation of K562 cells (p<0.05) and decreased miR181 expression, and increased caspase3 activity compared to the control group. It can induce K562 cell apoptosis via remarkably down-regulating mRNA and protein expressions of Bcl-2 (p<0.05).ConclusionsAs4S4 can facilitate K562 cell apoptosis via down-regulating miR181, inhibiting Bcl02 expression, and enhancing apoptotic protein caspase3 activity.

As4S4 Exhibits Good Killing Effect on Multiple Myeloma Cells Via Repressing SOCS1 Methylation-Mediated JAK2/STAT3 Signaling Pathway

“…11,23 Moreover, As 4 S 4 facilitates CML cell apoptosis through downregulating miR-181 as well as Bcl-2 expressions and promoting apoptotic protein Caspase-3 activity. 24 These studies emphasized the antiproliferative or proapoptotic function of As 4 S 4 in APL as well as CML, and we speculated that As 4 S 4 might also have good antitumor effect in other hematological malignancies, especially MM, while the effect of As 4 S 4 on MM cells was rarely reported. Thus, to investigate whether As 4 S 4 had killing effect on MM cells, we treated U266 cells with different concentrations of As 4 S 4 , and we found that As 4 S 4 repressed cell viability in a dose-/time-dependent manner in U266 cells, which may be due to (1) As 4 S 4 might induce MM cell apoptosis via promoting proapoptotic factor (such as PP2A) or inhibiting antiapoptotic factor (such as Bcl-2), thereby reduced MM cell viability; 11,24 (2) As 4 S 4 might regulate some downstream signaling pathways to decrease the cell viability, such as its downstream JAK2/STAT3 signaling pathway, which was displayed in our results.…”

“…Although the mechanisms of As 4 S 4 in solid tumors have been frequently explored, the current evidence about the mechanism of As 4 S 4 in hematological malignancies is mainly restricted to APL and CML. [22][23][24] For example, a previous study shows that As 4 S 4 inhibits cell proliferation and induces cell apoptosis via blocking the cell cycle in the S and G2/M phases in APL cells. 22 Besides, studies show that As 4 S 4 downregulates SET protein expression and further promotes the proapoptotic factor protein phosphatase 2A (PP2A) expression to enhance cell apoptosis and represses cell proliferation in a dose-/timedependent manner in APL cells.…”

Mineral medicine: from traditional drugs to multifunctional delivery systems

“…Inducing apoptosis of human liver cancer HepG2, QGY-7703 cells and blocking cell cycle G2/M progression [ 134 – 137 ]…”