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Arsenic trioxide inhibits the activity of SphK1 by decreasing the level of phosphatidylserine and phosphatidic acid in the human gastric cancer cell line MGC-803

Pei Liu,Zhe Chen,Xiaoqiong Ma

Published 2022 in Biocell (Mendoza)

ABSTRACT

Sphingosine kinase 1 (SphK1) is an important synthetase during the synthesis of sphingosine-1-phosphate (S1P) from sphingosine (Sph). Previous studies demonstrated that arsenic trioxide (As2O3) could reduce the level of S1P in human gastric cancer cell line MGC-803, indicating that As2O3 may inhibit the activity of SphK1. In this study, the effect of As2O3 on the SphK1 activation pathway was investigated. Western blot and quantitative real-time PCR analysis were used to evaluate the changes in protein and mRNA levels. The multi-dimensional mass spectrometry-based shotgun lipidomics method (MDMS-SL) was used for the quantitative detection of phosphatidylserine (PS) and phosphatidic acid (PA). The results revealed that As2O3 did not affect the protein and mRNA expression of SphK1 in the MGC-803 cells. However, As2O3 increased the levels of p-ERK1/2 and CIB1 in the SphK1 activation pathway and decreased the levels of PS and PA in the MGC-803 cells. The outcomes suggested that As2O3 may enhance the activity of SphK1 by increasing the levels of p-ERK1/2 and CIB1 and decrease the activity of SphK1 by decreasing the levels of PS and PA. It was suggested that the inhibition effect is stronger and resulting in an overall decrease in the activity of SphK1. Abbreviations As2O3: arsenic trioxide CIB1: calcium and integrin-binding protein 1 FBS: fetal bovine serum LPA: lysophosphatidic acid MDMS-SL: multi-dimensional mass spectrometry-based shotgun lipidomics MS: mass spectrometry NLS: neutral loss scan PA: phosphatidic acid p-ERK1/2: phosphorylated extracellular signal-regulated kinase 1 and 2 PIS: precursor ion scan PP2A: protein phosphatase 2A PS: phosphatidylserine QPCR: quantitative real-time polymerase chain reaction S1P: sphingosine 1-phosphate Sph: sphingosine SphK1: sphingosine kinase 1

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