Open Access

ARTICLE

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

by PEI LIU, ZHE CHEN, XIAOQIONG MA^*

Key Laboratory of Digestive Pathophysiology of Zhejiang Province, Institute of Cancer Research, First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China

* Corresponding Author:XIAOQIONG MA. Email:

BIOCELL 2022, 46(3), 737-743. https://doi.org/10.32604/biocell.2021.015786

Received 13 January 2021; Accepted 16 March 2021; Issue published 18 November 2021

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.

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