Review
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transl Med. Apr 12, 2016; 5(1): 37-45
Published online Apr 12, 2016. doi: 10.5528/wjtm.v5.i1.37
Sphingolipid metabolism affects the anticancer effect of cisplatin
Yu-Lan Li, Ming-Lin Lin, Song-Qing He, Jun-Fei Jin
Yu-Lan Li, Ming-Lin Lin, Song-Qing He, Jun-Fei Jin, Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
Yu-Lan Li, Ming-Lin Lin, Song-Qing He, Jun-Fei Jin, Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
Yu-Lan Li, Jun-Fei Jin, China-USA Lipids in Health and Disease Research Center, Guilin Medical University, Guilin 541001, Guangxi Zhuang Autonomous Region, China
Ming-Lin Lin, Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Author contributions: Li YL and Lin ML contributed equally to this work, drafted the figure and wrote the manuscript; He SQ contributed to the outline of the manuscript; Jin JF got the grants, planed the outline of this review, and revised the manuscript.
Conflict-of-interest statement: There was no conflict-of-interest to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jun-Fei Jin, PhD, Professor, Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, 15 Lequn Road, Guilin 541001, Guangxi Zhuang Autonomous Region, China. changliangzijin@163.com
Telephone: +86-773-2862270 Fax: +86-773-2810411
Received: August 27, 2015
Peer-review started: August 30, 2015
First decision: November 30, 2015
Revised: December 18, 2015
Accepted: January 8, 2016
Article in press: January 11, 2016
Published online: April 12, 2016
Processing time: 228 Days and 20.3 Hours
Abstract

Cisplatin, a DNA crosslinking agent, is widely used for the treatment of a variety of solid tumors. Numerous studies have demonstrated that sphingolipid metabolism, which acts as a target for cisplatin treatment, is a highly complex network that consists of sphingolipid signaling molecules and related catalytic enzymes. Ceramide (Cer), which is the central molecule of this network, has been established to induce apoptosis. However, another molecule, sphingosine-1-phosphate (S1P), exerts the opposite function, i.e., serves as a regulator of pro-survival. Other sphingolipid molecules, including dihydroceramide, ceramide-1-phosphate, glucosylceramide (GluCer), and sphingosine (Sph), or sphingolipid catalytic enzymes such as Sph kinase (SphK), Cer synthase (CerS), and S1P lyase, have also attracted considerable attention, particularly Cer, GluCer, SphK, CerS, and S1P lyase, which have been implicated in cisplatin resistance. This review summarizes specific molecules involved in sphingolipid metabolism and related catalytic enzymes affecting the anticancer effect of cisplatin, particularly in relation to induction of apoptosis and drug resistance.

Keywords: Apoptosis; Sphingolipid metabolism; Drug resistance; Cisplatin; Anticancer

Core tip: Cisplatin classifies as a classical anticancer drug and DNA is identified as the most important target of cisplatin. However, increasing evidences have testified that sphingolipid metabolism is associated with the anticancer effect of cisplatin. In this mini-review, we discussed sphingolipid signaling molecules and/or related enzymes affected the anticancer effect of cisplatin, particularly in cisplatin-induced cancer cell apoptosis and drug resistance. Targeting these sphingolipid molecules and enzymes might contribute to the development of novel anticancer strategies or to increase the sensitivity of currently used drugs.