Next Article in Journal
Microbial Communities and Bioactive Compounds in Marine Sponges of the Family Irciniidae—A Review
Previous Article in Journal
Chronic Toxicity Study of Neosaxitoxin in Rats
Previous Article in Special Issue
Another Facet to the Anticancer Response to Lamellarin D: Induction of Cellular Senescence through Inhibition of Topoisomerase I and Intracellular Ros Production
Article Menu

Export Article

Open AccessArticle
Mar. Drugs 2014, 12(9), 5072-5088; doi:10.3390/md12095072

Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway

1,2,†
,
3,†
,
1
,
1,2
,
4,* and 1,5,*
1
Institutes of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
2
Graduate School, University of Chinese Academy of Sciences, Beijing 100049, China
3
Department of Molecular Biology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China
4
Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China
5
Department of Pharmacology, Capital Medicine University, Beijing 100069, China
These two authors contribute equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 21 January 2014 / Revised: 14 April 2014 / Accepted: 15 April 2014 / Published: 25 September 2014
(This article belongs to the Special Issue Mechanism of Action Analysis for Marine Compounds)
View Full-Text   |   Download PDF [921 KB, uploaded 24 February 2015]   |  

Abstract

TNF-related apoptosis-inducing ligand (TRAIL) is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of some critical pro-survival proteins, such as survivin, is responsible for TRAIL resistance. In this study, we found that Aplysin, a brominated compound from marine organisms, was able to restore the sensitivity of cancer cells to TRAIL both in vitro and in vivo. Aplysin was found to enhance the tumor-suppressing capacity of TRAIL on several TRAIL-resistant cancer cell lines. TRAIL-induced apoptosis was also potentiated in A549 and MCF7 cells treated with Aplysin. Survivin downregulation was identified as a mechanism by which Aplysin-mediated TRAIL sensitization of cancer cells. Furthermore, the activation of p38 MAPK was revealed in Aplysin-treated cancer cells, and its inhibitor SB203580 was able to abrogate the promoting effect of Aplysin on the response of cancer cells to TRAIL action, as evidenced by restored survivin expression, elevated cell survival and reduced apoptotic rates. In conclusion, we provided evidence that Aplysin acts as a sensitizer for TRAIL and its effect on p38 MAPK/survivin pathway may partially account for this activity. Considering its low cytotoxicity to normal cells, Aplysin may be a promising agent for cancer treatment in combination with TRAIL. View Full-Text
Keywords: aplysin; TRAIL; p38 MAPK; survivin aplysin; TRAIL; p38 MAPK; survivin
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Liu, J.; Ma, L.; Wu, N.; Liu, G.; Zheng, L.; Lin, X. Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway. Mar. Drugs 2014, 12, 5072-5088.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top