title: Evaluation of the change in sphingolipids in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 treated with arsenic trioxide.
abstract: Arsenic trioxide (As2O3) has been found to display anticancer activity against many types of tumors and has been developed into an anticancer drug in clinical treatments. Sphingolipids are membrane lipids that participate in many signal transduction pathways. In this paper, the changes in sphingolipids of the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803 treated with arsenic trioxide were investigated using an HPLC-ESI-MS/MS method. Analytes were separated by an XBridge BEH C8 column used for Cer, HexCer, LacCer and SM chromatographic separation, and a Capcell PAK MG II C18 column was used for Sph, dhSph, S1P and dhS1P chromatographic separation and gradient elution with acetonitrile-water containing 0.1% formic acid as a mobile phase. A tandem mass spectrometer QTrap in SRM mode was employed in combination with RPLC as a detector for quantitative analysis. The ceramide/sphingolipid internal standard (IS) mixture was used to quantify the levels of sphingolipids. The distributions of sphingolipids were found to be different in the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803. Ceramide (Cer), hexosylceramide (HexCer) and dihexosylceramide (Hex2Cer) levels in U266 cell line are higher than those in MGC-803 cell line. Additionally, sphingomyelin (SM), sphingosine-1-phosphate (S1P) and sphinganine-1-phosphate (dhS1P) levels in the MGC-803 cell line are higher than those in the U266 cell line. When treated with arsenic trioxide (1-5μM iAs(III)(As(III) ions)), the levels of Hex2Cer in the human multiple myeloma cell line U266 decreased, and the levels of S1P and dhS1P in the human gastric cancer cell line MGC-803 decreased. The decrease of Hex2Cer, S1P and dhS1P in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 were observed when the concentration of iAs(III) is 1.0μM. Therefore, arsenic trioxide exhibits anti-cancer activity by altering the sphingolipid pathway in the human multiple myeloma cell line U266 and the gastric cancer cell line MGC-803.
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, 310006 Hangzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zou
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, 310006 Hangzhou, China. Electronic address: maxq126126@126.com.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Zhejiang Chinese Medical University College of Basic Medical Science, No. 548, Binwen Road, 310053 Hangzhou, China.
authors.forename: Guangji
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Zhejiang Chinese Medical University College of Basic Medical Science, No. 548, Binwen Road, 310053 Hangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.affiliation: Hangzhou Normal University College of Life and Environmental Sciences, No.16, Xuelin Road, 310036 Hangzhou, China.
authors.forename: Liting
authors.initials: L
authors.lastname: Zhou
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, 310006 Hangzhou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, 310006 Hangzhou, China.
authors.forename: Fanfan
authors.initials: F
authors.lastname: Zhu
authors.affiliation: The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, 310006 Hangzhou, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013107:Sphingolipids / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D053719:Tandem Mass Spectrometry
chemical_list: D001152:Arsenicals; D010087:Oxides; D013107:Sphingolipids; D000077237:Arsenic Trioxide
keywords: Arsenic trioxide; HPLC-ESI–MS/MS; Human gastric cancer cell line MGC-803; Human multiple myeloma cell line U266; Sphingolipids